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Sample records for gut incretin hormones

  1. GLP-1: broadening the incretin concept to involve gut motility.

    PubMed

    Hellström, Per M

    2009-08-01

    The incretin effect of the gut peptide hormone glucagon-like peptide-1 (GLP-1) is a combined result of inhibition of gastric emptying and stimulation of insulin secretion via an incretin mechanism. The temporal pattern of these events implicate that gastric emptying is primarily delayed, while later in the digestive process insulin is released for nutrient disposal. Since the inhibitory effect of GLP-1 on gastric motility is very outspoken, we considered it of value to study its effects on gut motility. Animal experimentation in the rat clearly showed that not only gastric emptying, but also small bowel motility with the migrating myoelectric complex was profoundly inhibited by GLP-1 at low doses. Similar effects were seen with analogues of the peptide. Extending the studies to man supported our earliest data indicating that the migrating motor complex of the small intestine was affected, and even more noticeable, the summarized motility index inhibited. Further extension of our studies to patients with irritable bowel syndrome (IBS) displayed similar results. This encouraged us to embark on a clinical pain-relief multi-centre study in IBS patients using a GLP-1 analogue, ROSE-010, with longer half-life than the native peptide. The outcome of the IBS study proved ROSE-010 to be superior to placebo with a pain-relief response rate of 24% for ROSE-010 compared to 12% for placebo. Taken together, the GLP-1 analogue ROSE-010 is believed to cause relaxation of the gut and can thereby relieve an acute pain attack of IBS, even though its precise mechanism is yet to be defined. PMID:19362109

  2. Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo.

    PubMed

    Fujita, Yukihiro; Wideman, Rhonda D; Speck, Madeleine; Asadi, Ali; King, David S; Webber, Travis D; Haneda, Masakazu; Kieffer, Timothy J

    2009-03-01

    Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are released during meals from endocrine cells located in the gut mucosa and stimulate insulin secretion from pancreatic beta-cells in a glucose-dependent manner. Although the gut epithelium senses luminal sugars, the mechanism of sugar sensing and its downstream events coupled to the release of the incretin hormones are not clearly elucidated. Recently, it was reported that sucralose, a sweetener that activates the sweet receptors of taste buds, triggers incretin release from a murine enteroendocrine cell line in vitro. We confirmed that immunoreactivity of alpha-gustducin, a key G-coupled protein involved in taste sensing, is sometimes colocalized with GIP in rat duodenum. We investigated whether secretion of incretins in response to carbohydrates is mediated via taste receptors by feeding rats the sweet-tasting compounds saccharin, acesulfame potassium, d-tryptophan, sucralose, or stevia. Oral gavage of these sweeteners did not reduce the blood glucose excursion to a subsequent intraperitoneal glucose tolerance test. Neither oral sucralose nor oral stevia reduced blood glucose levels in Zucker diabetic fatty rats. Finally, whereas oral glucose increased plasma GIP levels approximately 4-fold and GLP-1 levels approximately 2.5-fold postadministration, none of the sweeteners tested significantly increased levels of these incretins. Collectively, our findings do not support the concept that release of incretins from enteroendocrine cells is triggered by carbohydrates via a pathway identical to the sensation of "sweet taste" in the tongue. PMID:19106249

  3. Comparative effect of intraduodenal and intrajejunal glucose infusion on the gut-incretin axis response in healthy males.

    PubMed

    Wu, T; Thazhath, S S; Marathe, C S; Bound, M J; Jones, K L; Horowitz, M; Rayner, C K

    2015-01-01

    The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min(-1) over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was sampled frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI1 and the responses of GLP-1 and GIP (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1 (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut-incretin axis. PMID:25985092

  4. In Vivo Models for Incretin Research: From the Intestine to the Whole Body

    PubMed Central

    2016-01-01

    Incretin hormones are produced by enteroendocrine cells (EECs) in the intestine in response to ingested nutrient stimuli. The incretin effect is defined as the difference in the insulin secretory response between the oral glucose tolerance test and an isoglycemic intravenous glucose infusion study. The pathophysiology of the decreased incretin effect has been studied as decreased incretin sensitivity and/or β-cell dysfunction per se. Interestingly, robust increases in endogenous incretin secretion have been observed in many types of metabolic/bariatric surgery. Therefore, metabolic/bariatric surgery has been extensively studied for incretin physiology, not only the hormones themselves but also alterations in EECs distribution and genetic expression levels of gut hormones. These efforts have given us an enormous understanding of incretin biology from synthesis to in vivo behavior. Further innovative studies are needed to determine the mechanisms and targets of incretin hormones. PMID:26996422

  5. GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism

    PubMed Central

    Efanov, Alexander M.; Fang, Xiankang; Beavers, Lisa S.; Wang, Xuesong; Wang, Jingru; Gonzalez Valcarcel, Isabel C.; Ma, Tianwei

    2016-01-01

    GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a GPR142-dependent manner. In contrast, Phenylalanine improves in vivo glucose disposal independently of GPR142. Noteworthy, refeeding-induced elevations in insulin and glucose-dependent insulinotropic polypeptide are blunted in Gpr142 null mice. In conclusion, these findings demonstrate GPR142 is a Tryptophan receptor critically required for insulin and incretin hormone regulation and suggest GPR142 agonists may be effective therapies that leverage amino acid sensing pathways for the treatment of type 2 diabetes. PMID:27322810

  6. Stimulation of incretin secreting cells.

    PubMed

    Pais, Ramona; Gribble, Fiona M; Reimann, Frank

    2016-02-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system through transporters and G-protein coupled receptors (GPCRs) present on their surface to ultimately culminate in hormone release. Some of the molecules described below such as sodium coupled glucose transporter 1 (SGLT1), G-protein coupled receptor (GPR) 119 and GPR40 are targets of novel therapeutics designed to enhance endogenous gut hormone release. Synthetic ligands at these receptors aimed at treating obesity and type 2 diabetes are currently under investigation. PMID:26885360

  7. Stimulation of incretin secreting cells

    PubMed Central

    Pais, Ramona; Gribble, Fiona M.; Reimann, Frank

    2016-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system through transporters and G-protein coupled receptors (GPCRs) present on their surface to ultimately culminate in hormone release. Some of the molecules described below such as sodium coupled glucose transporter 1 (SGLT1), G-protein coupled receptor (GPR) 119 and GPR40 are targets of novel therapeutics designed to enhance endogenous gut hormone release. Synthetic ligands at these receptors aimed at treating obesity and type 2 diabetes are currently under investigation. PMID:26885360

  8. REVIEW: Role of cyclic AMP signaling in the production and function of the incretin hormone glucagon-like peptide-1

    NASA Astrophysics Data System (ADS)

    Yu, Zhiwen; Jin, Tianru

    2008-01-01

    Pancreatic cells express the proglucagon gene (gcg) and thereby produce the peptide hormone glucagon, which stimulates hepatic glucose production and thereby increases blood glucose levels. The same gcg gene is also expressed in the intestinal endocrine L cells and certain neural cells in the brain. In the gut, gcg expression leads to the production of glucagon-like peptide-1 (GLP-1). This incretin hormone stimulates insulin secretion when blood glucose level is high. In addition, GLP-1 stimulates pancreatic cell proliferation, inhibits cell apoptosis, and has been utilized in the trans-differentiation of insulin producing cells. Today, a long-term effective GLP-1 receptor agonist has been developed as a drug in treating diabetes and potentially other metabolic disorders. Extensive investigations have shown that the expression of gcg and the production of GLP-1 can be activated by the elevation of the second messenger cyclic AMP (cAMP). Recent studies suggest that in addition to protein kinase A (PKA), exchange protein activated by cAMP (Epac), another effector of cAMP signaling, and the crosstalk between PKA and Wnt signaling pathway, are also involved in cAMP-stimulated gcg expression and GLP-1 production. Furthermore, functions of GLP-1 in pancreatic cells are mainly mediated by cAMP-PKA, cAMP-Epac and Wnt signaling pathways as well.

  9. Connections Between the Gut Microbiome and Metabolic Hormones in Early Pregnancy in Overweight and Obese Women.

    PubMed

    Gomez-Arango, Luisa F; Barrett, Helen L; McIntyre, H David; Callaway, Leonie K; Morrison, Mark; Dekker Nitert, Marloes

    2016-08-01

    Overweight and obese women are at a higher risk for gestational diabetes mellitus. The gut microbiome could modulate metabolic health and may affect insulin resistance and lipid metabolism. The aim of this study was to reveal relationships between gut microbiome composition and circulating metabolic hormones in overweight and obese pregnant women at 16 weeks' gestation. Fecal microbiota profiles from overweight (n = 29) and obese (n = 41) pregnant women were assessed by 16S rRNA sequencing. Fasting metabolic hormone (insulin, C-peptide, glucagon, incretin, and adipokine) concentrations were measured using multiplex ELISA. Metabolic hormone levels as well as microbiome profiles differed between overweight and obese women. Furthermore, changes in some metabolic hormone levels were correlated with alterations in the relative abundance of specific microbes. Adipokine levels were strongly correlated with Ruminococcaceae and Lachnospiraceae, which are dominant families in energy metabolism. Insulin was positively correlated with the genus Collinsella. Gastrointestinal polypeptide was positively correlated with the genus Coprococcus but negatively with family Ruminococcaceae This study shows novel relationships between gut microbiome composition and the metabolic hormonal environment in overweight and obese pregnant women at 16 weeks' gestation. These results suggest that manipulation of the gut microbiome composition may influence pregnancy metabolism. PMID:27217482

  10. Incretin hormones and maturity onset diabetes of the young--pathophysiological implications and anti-diabetic treatment potential.

    PubMed

    Østoft, Signe Harring

    2015-09-01

    Maturity onset diabetes of the young (MODY) designates monogenic forms of non-autoimmune diabetes characterised by autosomal dominant inheritance, non-insulin dependent diabetes at onset and diagnosis often before 25 years of age. MODY constitutes genetically and clinically heterogeneous forms of diabetes. More than 8 different genes are known to cause MODY, among which hepatocyte nuclear factor 1 alpha (HNF1A) (MODY3) and glucokinase (GCK) (MODY2) mutations are the most common. Both forms of MODY are characterised by specific beta cell dysfunction, with patients with HNF1A-diabetes having a reduced insulin secretory capacity, while patients with GCK-diabetes have a glucose-sensing defect, but preserved insulin secretory capacity. Patients with MODY are effectively treated with sulphonylurea (SU) due to very high sensitivity to these drugs, but they are also prone to develop hypoglycaemia. The objectives of this thesis were to study the pathophysiology of GCK-diabetes and HNF1A-diabetes by investigating the incretin effect, the physiological response to food ingestion and to estimate the treatment potential of a glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with HNF1A-diabetes. In Study I we investigated the incretin effect and the responses of islet hormones and incretin hormones to oral glucose tolerance test (OGTT) and isoglycaemic IV glucose infusion (IIGI) in patients with GCK-diabetes, in patients with HNF1A-diabetes, and in BMI and age matched healthy individuals (CTRLs). In Study II we investigated responses of islet hormones and incretin hormones to a more physiological stimulus consisting of a standardised meal test in patients with GCK-diabetes, in patients with HNF1A--diabetes, and in BMI and age matched CTRLs. In Study III we conducted a randomised, double-blind, crossover trial investigating the glucose lowering effect and risk of hypoglycaemia during 6 weeks of treatment with the GLP-1RA, liraglutide compared to the SU, glimepiride

  11. Obestatin: an interesting but controversial gut hormone.

    PubMed

    Lacquaniti, Antonio; Donato, Valentina; Chirico, Valeria; Buemi, Antoine; Buemi, Michele

    2011-01-01

    Obestatin is a 23-amino acid peptide hormone released from the stomach and is present not only in the gastrointestinal tract, but also in the spleen, mammary gland, breast milk and plasma. Obestatin appears to function as part of a complex gut-brain network whereby hormones and substances from the stomach and intestines signal the brain about satiety or hunger. In contrast to ghrelin, which causes hyperphagia and obesity, obestatin appears to act as an anorectic hormone, decreasing food intake and reducing body weight gain. Further studies have shown that obestatin is also involved in improving memory, regulating sleep, affecting cell proliferation, increasing the secretion of pancreatic juice enzymes and inhibiting glucose-induced insulin secretion. This hormone has not only been studied in the field of physiology but also in the fields of obesity and diabetes mellitus, and in patients with psychogenic eating disorders. Obestatin has a role in regulating the cell cycle by exerting proliferative effects that may be seen in cell physiology and oncology. Given the current controversy regarding the effects of obestatin and its cognate ligand, this article provides the latest review of the physiological and pathological characteristics of this hormone. PMID:22156552

  12. Direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics.

    PubMed

    Karstoft, Kristian; Mortensen, Stefan P; Knudsen, Sine H; Solomon, Thomas P J

    2015-03-01

    The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n=10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg(-1)·min(-1)), and 3) glucose-dependent insulinotropic polypeptide (GIP, 1.5 pmol·kg(-1)·min(-1)). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P<0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P<0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels. PMID:25564476

  13. β-Cell Function, Incretin Effect, and Incretin Hormones in Obese Youth Along the Span of Glucose Tolerance From Normal to Prediabetes to Type 2 Diabetes

    PubMed Central

    Michaliszyn, Sara F.; Mari, Andrea; Lee, SoJung; Bacha, Fida; Tfayli, Hala; Farchoukh, Lama; Ferrannini, Ele

    2014-01-01

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-βCGS to the 2-h hyperglycemic clamp-βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia. PMID:24947360

  14. New physiological effects of the incretin hormones GLP-1 and GIP.

    PubMed

    Asmar, Meena

    2011-02-01

    With approximately 400 million people worldwide today being obese, we are facing a major public health problem due to the increasing prevalence of the related comorbidities such as type 2 diabetes, hypertension and coronary heart disease. To date, pharmacological treatment of obesity has been largely unsuccessful, only achieving modest and short-lasting reductions in body weight and with adverse effects. Scientific interest in recent years has concentrated on both the secretion and function of the incretin hormones, GLP-1 and GIP, and their suitability as new target drugs. The potential of GLP-1 to reduce gastric emptying, appetite and food intake makes it an attractive tool in the fight against obesity and several companies are developing weight lowering drugs based on GLP-1. Currently, it is not known whether the inhibiting effects of GLP-1 on gastric emptying, appetite and food intake are directly mediated by GLP-1, or if the effects are secondary to the robust insulin responses, and thereby amylin responses, elicited by GLP-1. The first study aimed to further elucidate the mechanisms of these effects in order to strengthen the development of anti-diabetic drugs with potential weight lowering capabilities. We found that GLP-1 mediates its effect on gastrointestinal motility, appetite, food intake and glucagon secretion directly and thereby in an amylin-independent fashion. In vitro and animal studies indicate that GIP exerts direct effects on adipose tissue and lipid metabolism, promoting fat deposition. Due to its therapeutic potential in obesity treatment, a rapidly increasing number of functional studies are investigating effects of acute and chronic loss of GIP signaling in glucose and lipid homeostasis. However, the physiological significance of GIP as a regulator of lipid metabolism in humans remains unclear. In the second study, we investigated the effects of GIP on the removal rate of plasma TAG and FFA concentrations, which were increased after either a

  15. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice.

    PubMed

    Gunnarsson, P Thomas; Winzell, Maria Sörhede; Deacon, Carolyn F; Larsen, Marianne O; Jelic, Katarina; Carr, Richard D; Ahrén, Bo

    2006-07-01

    Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P < 0.01), which was associated with enhanced oral glucose tolerance (P < 0.01). The insulin response to glucose was also augmented by addition of OA (34 mg; P < 0.05) although only 1.5-fold and with no associated increase in glucose elimination. The slope of the glucose-insulin curve was increased by OA (1.7-fold; P < 0.05) and by WP (4-fold; P < 0.01) compared with glucose alone, suggesting potentiation of glucose-stimulated insulin release. WP increased GLP-1 secretion (P < 0.01), whereas GIP secretion was unaffected. OA did not affect GIP or GLP-1 secretion. Nevertheless, WP increased the levels of both intact GIP and intact GLP-1 (both P < 0.01), and OA increased the levels of intact GLP-1 (P < 0.05). WP inhibited dipeptidyl peptidase IV activity in the proximal small intestine by 50% (P < 0.05), suggesting that luminal degradation of WP generates small fragments, which are substrates for dipeptidyl peptidase IV and act as competitive inhibitors. We therefore conclude that fat and protein may serve as exogenous regulators of secretion and inactivation of the incretin hormones with beneficial influences on glucose metabolism. PMID:16627575

  16. Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

  17. Gut hormones: emerging role in immune activation and inflammation.

    PubMed

    Khan, W I; Ghia, J E

    2010-07-01

    Gut inflammation is characterized by mucosal recruitment of activated cells from both the innate and adaptive immune systems. In addition to immune cells, inflammation in the gut is associated with an alteration in enteric endocrine cells and various biologically active compounds produced by these cells. Although the change in enteric endocrine cells or their products is considered to be important in regulating gut physiology (motility and secretion), it is not clear whether the change plays any role in immune activation and in the regulation of gut inflammation. Due to the strategic location of enteric endocrine cells in gut mucosa, these gut hormones may play an important role in immune activation and promotion of inflammation in the gut. This review addresses the research on the interface between immune and endocrine systems in gastrointestinal (GI) pathophysiology, specifically in the context of two major products of enteric endocrine systems, namely serotonin (5-hydroxytryptamine: 5-HT) and chromogranins (Cgs), in relation to immune activation and generation of inflammation. The studies reviewed in this paper demonstrate that 5-HT activates the immune cells to produce proinflammatory mediators and by manipulating the 5-HT system it is possible to modulate gut inflammation. In the case of Cgs the scenario is more complex, as this hormone has been shown to play both proinflammatory and anti-inflammatory functions. It is also possible that interaction between 5-HT and Cgs may play a role in the modulation of immune and inflammatory responses. In addition to enhancing our understanding of immunoendocrine interaction in the gut, the data generated from the these studies may have implications in understanding the role of gut hormone in the pathogenesis of both GI and non-GI inflammatory diseases which may lead ultimately to improved therapeutic strategies in inflammatory disorders. PMID:20408856

  18. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    PubMed Central

    Mikkelsen, Kristian H.; Frost, Morten; Bahl, Martin I.; Licht, Tine R.; Jensen, Ulrich S.; Rosenberg, Jacob; Pedersen, Oluf; Hansen, Torben; Rehfeld, Jens F.; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.

    2015-01-01

    Objective The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Methods Meal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Results Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. Conclusion As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. Trial Registration clinicaltrials.gov NCT01633762 PMID:26562532

  19. The antidiabetic action of camel milk in experimental type 2 diabetes mellitus: an overview on the changes in incretin hormones, insulin resistance, and inflammatory cytokines.

    PubMed

    Korish, A A

    2014-06-01

    Folk medicine stories accredited the aptitude of camel milk (CMK) as a hypoglycemic agent and recent studies have confirmed this in the diabetic patients and experimental animals. However, the mechanism(s) by which CMK influences glucose homeostasis is yet unclear. The current study investigated the changes in the glucose homeostatic parameters, the incretin hormones, and the inflammatory cytokines in the CMK-treated diabetic animals. A model of type 2 diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin 40 mg/kg/day for 4 repeated doses. Camel milk treatment was administered for 8 weeks. The changes in glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic peptide (GIP), glucose tolerance, fasting and glucose-stimulated insulin secretion, insulin resistance (IR), TNF-α, TGF-β1, lipid profile, atherogenic index (AI), and body weight were investigated. The untreated diabetic animals showed hyperglycemia, increased HOMA-IR, hyperlipidemia, elevated AI, high serum incretins [GLP-1 and GIP], TNF-α, and TGF-β1 levels and weight loss as compared with the control group. Camel milk treatment to the diabetic animals resulted in significant lowered fasting glucose level, hypolipidemia, decreased HOMA-IR, recovery of insulin secretion, weight gain, and no mortality during the study. Additionally, CMK inhibits the diabetes-induced elevation in incretin hormones, TNF-α and TGF-β1 levels. The increase in glucose-stimulated insulin secretion, decreased HOMA-IR, modulation of the secretion and/or the action of incretins, and the anti-inflammatory effect are anticipated mechanisms to the antidiabetic effect of CMK and suggest it as a valuable adjuvant antidiabetic therapy. PMID:24627103

  20. Gastrointestinal hormones and the dialogue between gut and brain

    PubMed Central

    Dockray, Graham J

    2014-01-01

    The landmark discovery by Bayliss and Starling in 1902 of the first hormone, secretin, emerged from earlier observations that a response (pancreatic secretion) following a stimulus (intestinal acidification) occurred after section of the relevant afferent nerve pathway. Nearly 80 years elapsed before it became clear that visceral afferent neurons could themselves also be targets for gut and other hormones. The action of gut hormones on vagal afferent neurons is now recognised to be an early step in controlling nutrient delivery to the intestine by regulating food intake and gastric emptying. Interest in these mechanisms has grown rapidly in view of the alarming global increase in obesity. Several of the gut hormones (cholecystokinin (CCK); peptide YY3–36 (PYY3–36); glucagon-like peptide-1 (GLP-1)) excite vagal afferent neurons to activate an ascending pathway leading to inhibition of food intake. Conversely others, e.g. ghrelin, that are released in the inter-digestive period, inhibit vagal afferent neurons leading to increased food intake. Nutrient status determines the neurochemical phenotype of vagal afferent neurons by regulating a switch between states that promote orexigenic or anorexigenic signalling through mechanisms mediated, at least partly, by CCK. Gut–brain signalling is also influenced by leptin, by gut inflammation and by shifts in the gut microbiota including those that occur in obesity. Moreover, there is emerging evidence that diet-induced obesity locks the phenotype of vagal afferent neurons in a state similar to that normally occurring during fasting. Vagal afferent neurons are therefore early integrators of peripheral signals underling homeostatic mechanisms controlling nutrient intake. They may also provide new targets in developing treatments for obesity and feeding disorders. PMID:24566540

  1. The Role of Incretins in Glucose Homeostasis and Diabetes Treatment

    PubMed Central

    Kim, Wook; Egan, Josephine M.

    2009-01-01

    Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating. In this manner, as well as others to be described in this review, their final common raison d’être is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to β-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their

  2. The incretin system ABCs in obesity and diabetes - novel therapeutic strategies for weight loss and beyond.

    PubMed

    João, A L; Reis, F; Fernandes, R

    2016-07-01

    Incretins are gastrointestinal-derived hormones released in response to a meal playing a key role in the regulation of postprandial secretion of insulin (incretin effect) and glucagon by the pancreas. Both incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), have several other actions by peripheral and central mechanisms. GLP-1 regulates body weight by inhibiting appetite and delaying gastric, emptying actions that are dependent on central nervous system GLP-1 receptor activation. Several other hormones and gut peptides, including leptin and ghrelin, interact with GLP-1 to modulate appetite. GLP-1 is rapidly degraded by the multifunctional enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 is involved in adipose tissue inflammation, which is associated with insulin resistance and diabetes progression, being a common pathophysiological mechanism in obesity-related complications. Furthermore, the incretin system appears to provide the basis for understanding the high weight loss efficacy of bariatric surgery, a widely used treatment for obesity, often in association with diabetes. The present review brings together new insights into obesity pathogenesis, integrating GLP-1 and DPP-4 in the complex interplay between obesity and inflammation, namely, in diabetic patients. This in turn will provide the basis for novel incretin-based therapeutic strategies for obesity and diabetes with promising benefits in addition to weight loss. © 2016 World Obesity. PMID:27125902

  3. Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects.

    PubMed

    Wölnerhanssen, Bettina K; Cajacob, Lucian; Keller, Nino; Doody, Alison; Rehfeld, Jens F; Drewe, Juergen; Peterli, Ralph; Beglinger, Christoph; Meyer-Gerspach, Anne Christin

    2016-06-01

    With the increasing prevalence of obesity and a possible association with increasing sucrose consumption, nonnutritive sweeteners are gaining popularity. Given that some studies indicate that artificial sweeteners might have adverse effects, alternative solutions are sought. Xylitol and erythritol have been known for a long time and their beneficial effects on caries prevention and potential health benefits in diabetic patients have been demonstrated in several studies. Glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are released from the gut in response to food intake, promote satiation, reduce gastric emptying (GE), and modulate glucose homeostasis. Although glucose ingestion stimulates sweet taste receptors in the gut and leads to incretin and gastrointestinal hormone release, the effects of xylitol and erythritol have not been well studied. Ten lean and 10 obese volunteers were given 75 g of glucose, 50 g of xylitol, or 75 g of erythritol in 300 ml of water or placebo (water) by a nasogastric tube. We examined plasma glucose, insulin, active GLP-1, CCK, and GE with a [(13)C]sodium acetate breath test and assessed subjective feelings of satiation. Xylitol and erythritol led to a marked increase in CCK and GLP-1, whereas insulin and plasma glucose were not (erythritol) or only slightly (xylitol) affected. Both xylitol and erythritol induced a significant retardation in GE. Subjective feelings of appetite were not significantly different after carbohydrate intake compared with placebo. In conclusion, acute ingestion of erythritol and xylitol stimulates gut hormone release and slows down gastric emptying, whereas there is no or only little effect on insulin release. PMID:27117004

  4. Obesity: An overview of possible role(s) of gut hormones, lipid sensing and gut microbiota.

    PubMed

    Mishra, Alok Kumar; Dubey, Vinay; Ghosh, Asit Ranjan

    2016-01-01

    Obesity is one of the major challenges for public health in 21st century, with 1.9 billion people being considered as overweight and 600 million as obese. There are certain diseases such as type 2 diabetes, hypertension, cardiovascular disease, and several forms of cancer which were found to be associated with obesity. Therefore, understanding the key molecular mechanisms involved in the pathogenesis of obesity could be beneficial for the development of a therapeutic approach. Hormones such as ghrelin, glucagon like peptide 1 (GLP-1) peptide YY (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK) secreted by an endocrine organ gut, have an intense impact on energy balance and maintenance of homeostasis by inducing satiety and meal termination. Glucose and energy homeostasis are also affected by lipid sensing in which different organs respond in different ways. However, there is one common mechanism i.e. formation of esterified lipids (long chain fatty acyl CoAs) and the activation of protein kinase C δ (PKC δ) involved in all these organs. The possible role of gut microbiota and obesity has been addressed by several researchers in recent years, indicating the possible therapeutic approach toward the management of obesity by the introduction of an external living system such as a probiotic. The proposed mechanism behind this activity is attributed by metabolites produced by gut microbial organisms. Thus, this review summarizes the role of various physiological factors such as gut hormone and lipid sensing involved in various tissues and organ and most important by the role of gut microbiota in weight management. PMID:26683796

  5. Effects of Diet Soda on Gut Hormones in Youths With Diabetes

    PubMed Central

    Brown, Rebecca J.; Walter, Mary; Rother, Kristina I.

    2012-01-01

    OBJECTIVE In patients with type 2 diabetes, but not type 1 diabetes, abnormal secretion of incretins in response to oral nutrients has been described. In healthy youths, we recently reported accentuated glucagon-like peptide 1 (GLP-1) secretion in response to a diet soda sweetened with sucralose and acesulfame-K. In this study, we examined the effect of diet soda on gut hormones in youths with diabetes. RESEARCH DESIGN AND METHODS Subjects aged 12–25 years with type 1 diabetes (n = 9) or type 2 diabetes (n = 10), or healthy control participants (n = 25) drank 240 mL cola-flavored caffeine-free diet soda or carbonated water, followed by a 75-g glucose load, in a randomized, cross-over design. Glucose, C-peptide, GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide Tyr-Tyr (PYY) were measured for 180 min. Glucose and GLP-1 have previously been reported for the healthy control subjects. RESULTS GLP-1 area under the curve (AUC) was 43% higher after ingestion of diet soda versus carbonated water in individuals with type 1 diabetes (P = 0.020), similar to control subjects (34% higher, P = 0.029), but was unaffected by diet soda in patients with type 2 diabetes (P = 0.92). Glucose, C-peptide, GIP, and PYY AUC were not statistically different between the two conditions in any group. CONCLUSIONS Ingestion of diet soda before a glucose load augmented GLP-1 secretion in type 1 diabetic and control subjects but not type 2 diabetic subjects. GIP and PYY secretion were not affected by diet soda. The clinical significance of this increased GLP-1 secretion, and its absence in youths with type 2 diabetes, needs to be determined. PMID:22410815

  6. Incretin based therapies: A novel treatment approach for non-alcoholic fatty liver disease

    PubMed Central

    Blaslov, Kristina; Bulum, Tomislav; Zibar, Karin; Duvnjak, Lea

    2014-01-01

    Non-alcoholic fatty liver disease is considered a hepatic manifestation of metabolic syndrome (MS). The current treatment of non-alcoholic fatty liver disease (NAFLD) principally includes amelioration of MS components by lifestyle modifications but the lack of success in their implementation and sustainment arises the need for effective pharmacological agent in fatty liver treatment. Incretins are gut derived hormones secreted into the circulation in response to nutrient ingestion that enhances glucose-stimulated insulin secretion. Glucagon-like peptide-1 (GLP-1) is the most important incretin. Its receptor agonist and inhibitors of dipeptidyl peptidase-4 (DPP-4) are used in treatment of type 2 diabetes mellitus. DPP-4 serum activity and hepatic expression are shown to be elevated in several hepatic diseases. There are several experimental and clinical trials exploring the efficacy of incretin based therapies in NAFLD treatment. They suggest that GLP-1 analogues might have beneficial effect on hepatic steatosis acting as insulin sensitizers and directly by stimulating GLP-1 receptors expressed on hepatocytes. The use of DPP-4 inhibitors also results in hepatic fat reduction but the mechanism of action remains unclear. There is growing evidence that incretin based therapies have beneficial effects on hepatocytes, however further study analysis are needed to assess the long term effect of incretin based therapies on NAFLD. PMID:24966606

  7. New insight into the mechanisms underlying the function of the incretin hormone glucagon-like peptide-1 in pancreatic β-cells

    PubMed Central

    Xiong, Xiaoquan; Shao, Weijuan; Jin, Tianru

    2012-01-01

    During the past two decades, the exploration of function of two incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), has led to the development of two categories of novel therapeutic agents for diabetes and its complications, known as GLP-1 receptor (GLP-1R) agonists and DPP-IV inhibitors. Mechanisms underlying the function of GLP-1, however, still need to be further explored. GLP-1 not only functions as an incretin hormone in stimulating insulin secretion in response to nutritional, hormonal and neuronal stimulations, but also acts as an “insulin-like” factor in β-cell and extra-pancreatic organs. In addition to these insulinotropic and insulinomimetic effects, GLP-1 was shown to exert its protective effect in β-cell by repressing the expression of TxNIP, a mediator of glucolipotoxicity. A number of recent studies have shown that the Wnt signaling pathway effector, the bipartite transcription factor β-catenin/TCF, controls not only the production of GLP-1, but also the function of GLP-1. Furthermore, previously assumed “degradation” products of GLP-1(7–36)amide, including GLP-1(9–36)amide and GLP-1(28–36)amide, have been shown to exert beneficial effect in pancreas and extra-pancreatic tissues or cell lineages. Here we summarized our current knowledge on the metabolic, proliferative and protective effects of GLP-1(7–36)amide and its cleavage fragments, mainly focusing on pancreatic β-cells and the involvement of the Wnt signaling pathway effector β-catenin. PMID:23314611

  8. Do Incretins Play a Role in the Remission of Type 2 Diabetes after Gastric Bypass Surgery: What are the Evidence?

    PubMed Central

    Bose, Mousumi; Oliván, Blanca; Teixeira, Julio; Pi-Sunyer, F. Xavier; Laferrère, Blandine

    2010-01-01

    Gastric bypass surgery (GBP), in addition to weight loss, results in dramatic remission of type 2 diabetes (T2DM). The mechanisms by which this remission occurs are unclear. Besides weight loss and caloric restriction, the changes in gut hormones that occur after GBP are increasingly gaining recognition as key players in glucose control. Incretins are gut peptides that stimulate insulin secretion postprandially; the levels of these hormones, particularly glucagon-like peptide-1, increase after GBP in response to nutrient stimulation. Whether these changes are causal to changes in glucose homeostasis remain to be determined. The purpose of this review is to assess the evidence on incretin changes and T2DM remission after GBP, and the possible mechanisms by which these changes occur. Our goals are to provide a thorough update on this field of research so that recommendations for future research and criteria for bariatric surgery can be evaluated. PMID:18820978

  9. Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

    PubMed

    Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

    2016-06-01

    Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future. PMID:27234550

  10. Diabetes and obesity treatment based on dual incretin receptor activation: 'twincretins'.

    PubMed

    Skow, M A; Bergmann, N C; Knop, F K

    2016-09-01

    The gut incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted after meal ingestion and work in concert to promote postprandial insulin secretion and regulate glucagon secretion. GLP-1 also slows gastric emptying and suppresses appetite, whereas GIP seems to affect lipid metabolism. The introduction of selective GLP-1 receptor (GLP-1R) agonists for the treatment of type 2 diabetes and obesity has increased the scientific and clinical interest in incretins. Combining the body weight-lowering and glucose-lowering effects of GLP-1 with a more potent improvement of β cell function through additional GIP action could potentially offer a more effective treatment of diabetes and obesity, with fewer adverse effects than selective GLP-1R agonists; therefore, new drugs designed to co-activate both the GIP receptor (GIPR) and the GLP-1R simultaneously are under development. In the present review, we address advances in the field of GIPR and GLP-1R co-agonism and review in vitro studies, animal studies and human trials involving co-administration of the two incretins, as well as results from a recently developed GIPR/GLP-1R co-agonist, and highlight promising areas and challenges within the field of incretin dual agonists. PMID:27160961

  11. (−)-Epigallocatechin-3-gallate induces secretion of anorexigenic gut hormones

    PubMed Central

    Song, Won-Young; Aihara, Yoshiko; Hashimoto, Takashi; Kanazawa, Kazuki; Mizuno, Masashi

    2015-01-01

    The anorexigenic gut hormones, cholecystokinin (CCK), glucagon-like peptide (GLP)-1 and peptide tyrosine-tyrosine (PYY), are released in response to food intake from the intestines. Dietary nutrients have been shown to stimulate these hormones. Some non-nutrients such as polyphenols show anorexigenic effects on humans. In the present study, we examined whether dietary polyphenols can stimulate secretion of these gut hormones. Caco-2 cells expressed mRNA of the gut hormones, CCK, PC1 (prohormone convertase 1), GCG (glucagon) and PYY. CCK, GLP-1 and PYY were secreted from Caco-2 cells after adding sugars, amino acids or fatty acids. Using Caco-2 cells, epigallocatechin-3-gallate (EGCG), chlorogenic acid and ferulic acid induced secretion of anorexigenic gut hormones. Particularly, EGCG induced secretion of all three hormones. In an ex vivo assay using murine intestines, EGCG also released CCK from the duodenum, and GLP-1 from the ileum. These results suggest that EGCG may affect appetite via gut hormones. PMID:26388676

  12. Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion?

    PubMed

    Finelli, Carmine; Padula, Maria Carmela; Martelli, Giuseppe; Tarantino, Giovanni

    2014-11-28

    Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures - as diets, physical activity, behavior therapy and pharmacotherapy - have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical. PMID:25469034

  13. Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion?

    PubMed Central

    Finelli, Carmine; Padula, Maria Carmela; Martelli, Giuseppe; Tarantino, Giovanni

    2014-01-01

    Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures - as diets, physical activity, behavior therapy and pharmacotherapy - have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical. PMID:25469034

  14. Incretins, Pregnancy, and Gestational Diabetes.

    PubMed

    Nikolic, Dragana; Al-Rasadi, Khalid; Al Busaidi, Noor; Al-Waili, Khalid; Banerjee, Yajnavalka; Al-Hashmi, Khamis; Montalto, Giuseppe; Rizvi, Ali A; Rizzo, Manfredi; Al-Dughaishi, Tamima

    2016-01-01

    The number of pregnant women affected by gestational diabetes mellitus (GDM) is increasing among Caucasians, and East Asians. GDM also increases the risk for later advent of type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease in both women and their offspring. The underlying mechanism of GDM is not fully elucidated. Incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been suggested to have a role in maternal metabolism and weight as well as fetal growth. These hormones might be implicated in mechanisms that compensate for the increment in glycemia and insulin resistance seen during pregnancy, while other factors, such as heredity, environment and lifestyle, but also different race/ethnic background might also lead to the comorbid health problems. Some studies indicate that pregnancy is associated with a diminished GLP-1 response which is more prominently evident in women with GDM and normalizes after delivery. Postprandial GIP level seems to be unaffected by pregnancy, despite its increased level in GDM. On the other hand, the reduced incretin effect observed in GDM may represent a risk factor for obesity, T2DM and metabolic disorders even in the offspring of these women. Further investigations are needed to establish the exact role of incretins in pregnancy and gestational glucose intolerance. PMID:26813306

  15. Vagal and hormonal gut-brain communication: from satiation to satisfaction.

    PubMed

    Berthoud, H-R

    2008-05-01

    Studying communication between the gut and the brain is as relevant and exciting as it has been since Pavlov's discoveries a century ago. Although the efferent limb of this communication has witnessed significant advances, it is the afferent, or sensory, limb that has recently made for exciting news. It is now clear that signals from the gut are crucial for the control of appetite and the regulation of energy balance, glucose homeostasis, and more. Ghrelin, discovered just a few years ago, is the first gut hormone that increases appetite, and it may be involved in eating disorders. The stable analogue of glucagon-like peptide-1 has rapidly advanced to one of the most promising treatment options for type-2 diabetes. Changes in the signalling patterns of these and other gut hormones best explain the remarkable capacity of gastric bypass surgery to lower food intake and excess body weight. Given the enormous societal implications of the obesity epidemic, these are no small feats. Together with the older gut hormone cholecystokinin and abundant vagal mechanosensors, the gut continuously sends information to the brain regarding the quality and quantity of ingested nutrients, not only important for satiation and meal termination, but also for the appetitive phase of ingestive behaviour and the patterning of meals within given environmental constraints. By acting not only on brainstem and hypothalamus, this stream of sensory information from the gut to the brain is in a position to generate a feeling of satisfaction and happiness as observed after a satiating meal and exploited in vagal afferent stimulation for depression. PMID:18402643

  16. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?

    PubMed

    Lean, M E J; Malkova, D

    2016-04-01

    The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones. Homeostatic control of food intake occurs in humans, although its relative importance for eating behaviour is uncertain, compared with social and environmental influences. There are perturbations in the gut-brain axis in obese compared with lean individuals, as well as in weight-reduced obese individuals. Fasting and postprandial levels of gut hormones change when obese individuals lose weight, either with surgical or with dietary and/or exercise interventions. Diet-induced weight loss results in long-term changes in appetite gut hormones, postulated to favour increased appetite and weight regain while exercise programmes modify responses in a direction expected to enhance satiety and permit weight loss and/or maintenance. Sustained weight loss achieved by bariatric surgery may in part be mediated via favourable changes to gut hormones. Future work will be necessary to fully elucidate the role of each element of the axis, and whether modifying these signals can reduce the risk of obesity. PMID:26499438

  17. Stimulation of incretin secretion by dietary lipid: is it dose dependent?

    PubMed

    Yoder, Stephanie M; Yang, Qing; Kindel, Tammy L; Tso, Patrick

    2009-08-01

    After the ingestion of nutrients, secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) by the enteroendocrine cells increases rapidly. Previous studies have shown that oral ingestion of fat stimulates secretion of both incretins; however, it is unclear whether there is a dose-dependent relationship between the amount of lipid ingested and the secretion of the hormones in vivo. Recently, we found a higher concentration of the incretin hormones in intestinal lymph than in peripheral or portal plasma. We therefore used the lymph fistula rat model to test for a dose-dependent relationship between the secretion of GIP and GLP-1 and dietary lipid. Under isoflurane anesthesia, the major mesenteric lymphatic duct of male Sprague-Dawley rats was cannulated. Each animal received a single, intraduodenal bolus of saline or varying amounts of the fat emulsion Liposyn II (0.275, 0.55, 1.1, 2.2, and 4.4 kcal). Lymph was continuously collected for 3 h and analyzed for triglyceride, GIP, and GLP-1 content. In response to increasing lipid calories, secretion of triglyceride, GIP, and GLP-1 into lymph increased dose dependently. Interestingly, the response to changes in intraluminal lipid content was greater in GLP-1- than in GIP-secreting cells. The different sensitivities of the two cell types to changes in intestinal lipid support the concept that separate mechanisms may underlie lipid-induced GIP and GLP-1 secretion. Furthermore, we speculate that the increased sensitivity of GLP-1 to intestinal lipid content reflects the hormone's role in the ileal brake reflex. As lipid reaches the distal portion of the gut, GLP-1 is secreted in a dose-dependent manner to reduce intestinal motility and enhance proximal fat absorption. PMID:19520739

  18. Physiological mechanisms of action of incretin and insulin in regulating skeletal muscle metabolism.

    PubMed

    Abdulla, Haitham; Phillips, Bethan; Smith, Kenneth; Wilkinson, Daniel; Atherton, Philip J; Idris, Iskandar

    2014-01-01

    Type II diabetes (T2D) is a progressive condition affecting approximately 350 million adults worldwide. Whilst skeletal muscle insulin resistance and beta-cell dysfunction are recognised causes of T2D, progressive loss of lean muscle mass (reducing surface area for glucose disposal area) in tandem with ageing-related adiposity (i.e. sarcopenic obesity) also plays an important role in driving hyperglycaemia progression. The anabolic effects of nutrition on the muscle are driven by the uptake of amino acids, into skeletal muscle protein, and insulin plays a crucial role in regulating this. Meanwhile glucagon-like peptide (GLP-1) and glucose- dependent insulinotropic peptide (GIP) are incretin hormones released from the gut into the bloodstream in response to macronutrients, and have an established role in enhancing insulin secretion. Intriguingly, endocrine functions of incretins were recently shown to extend beyond classical insulinotropic effects, with GLP-1/GIP receptors being found in extra-pancreatic cells i.e., skeletal muscle and peripheral (muscle) microvasculature. Since, incretins have been shown to modulate blood flow and muscle glucose uptake in an insulin-independent manner, incretins may play a role in regulating nutrient-mediated modulation of muscle metabolism and microvascular tone, independently of their insulinotropic effects. In this review we will discuss the role of skeletal muscle in glucose homeostasis, disturbances related to insulin resistance, regulation of skeletal muscle metabolism, muscle microvascular abnormalities and disturbances of protein (PRO) metabolism seen in old age and T2D. We will also discuss the emerging non-insulinotropic role of GLP-1 in modulating skeletal muscle metabolism and microvascular blood flow. PMID:25323297

  19. Pleiotropic effects of incretins

    PubMed Central

    Gupta, Vishal

    2012-01-01

    Drugs that augment the incretin system [glucagon like peptide (GLP) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors] represent a novel class of anti-hyperglycemic agents that have shown to improve the health and survival of beta-cells (improvement in postprandial hyperglycemia) and suppress glucagon (improvement in fasting hyperglycemia). The incretins represent a large family of molecules referred to as the “glucagon superfamily of peptide hormones” of which more than 90% of the physiological effects of incretins are accomplished by GLP-17-37 and GLP17-36 amide and gastric insulinotropic peptide (GIP). GLP-1 mediates its effects via the GLP-1 receptor, which has a wide tissue distribution [pancreas, lung, heart, vascular smooth muscle cells, endothelial cells, macrophages and monocytes, kidney, gastrointestinal tract (stomach and intestine), central nervous system (neoortex, cerebellum, hypothalamus, hippocampus, brainstem nucleus tractus solitarius) and peripheral nervous system]. This would imply that the incretin system has effects outside the pancreas. Over time data has accumulated to suggest that therapies that augment the incretin system has beneficial pleiotrophic effects. The incretins have shown to possess a cardiac-friendly profile, preserve neuronal cells and safeguard from neuronal degeneration, improve hepatic inflammation and hepatosteatosis, improve insulin resistance, promote weight loss and induce satiety. There is growing evidence that they may also be renoprotective promoting wound healing and bone health. PMID:22701844

  20. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?

    PubMed Central

    Lean, M E J; Malkova, D

    2016-01-01

    The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut–brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones. Homeostatic control of food intake occurs in humans, although its relative importance for eating behaviour is uncertain, compared with social and environmental influences. There are perturbations in the gut–brain axis in obese compared with lean individuals, as well as in weight-reduced obese individuals. Fasting and postprandial levels of gut hormones change when obese individuals lose weight, either with surgical or with dietary and/or exercise interventions. Diet-induced weight loss results in long-term changes in appetite gut hormones, postulated to favour increased appetite and weight regain while exercise programmes modify responses in a direction expected to enhance satiety and permit weight loss and/or maintenance. Sustained weight loss achieved by bariatric surgery may in part be mediated via favourable changes to gut hormones. Future work will be necessary to fully elucidate the role of each element of the axis, and whether modifying these signals can reduce the risk of obesity. PMID:26499438

  1. Effects of GLP-1 and Incretin-Based Therapies on Gastrointestinal Motor Function

    PubMed Central

    Marathe, Chinmay S.; Rayner, Christopher K.; Jones, Karen L.; Horowitz, Michael

    2011-01-01

    Glucagon-like peptide 1 (GLP-1) is a hormone secreted predominantly by the distal small intestine and colon and released in response to enteral nutrient exposure. GLP-1-based therapies are now used widely in the management of type 2 diabetes and have the potential to be effective antiobesity agents. Although widely known as an incretin hormone, there is a growing body of evidence that GLP-1 also acts as an enterogastrone, with profound effects on the gastrointestinal motor system. Moreover, the effects of GLP-1 on gastrointestinal motility appear to be pivotal to its effect of reducing postprandial glycaemic excursions and may, potentially, represent the dominant mechanism. This review summarizes current knowledge of the enterogastrone properties of GLP-1, focusing on its effects on gut motility at physiological and pharmacological concentrations, and the motor actions of incretin-based therapies. While of potential importance, the inhibitory action of GLP-1 on gastric acid secretion is beyond the scope of this paper. PMID:21747825

  2. The incretin hormone glucagon‐like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage‐dependent potassium channel

    PubMed Central

    Llewellyn‐Smith, Ida J.; Gribble, Fiona; Reimann, Frank; Trapp, Stefan; Fadool, Debra Ann

    2016-01-01

    Key points The gut hormone called glucagon‐like peptide 1 (GLP‐1) is a strong moderator of energy homeostasis and communication between the peripheral organs and the brain.GLP‐1 signalling occurs in the brain; using a newly developed genetic reporter line of mice, we have discovered GLP‐synthesizing cells in the olfactory bulb.GLP‐1 increases the firing frequency of neurons (mitral cells) that encode olfactory information by decreasing activity of voltage‐dependent K channels (Kv1.3).Modifying GLP‐1 levels, either therapeutically or following the ingestion of food, could alter the excitability of neurons in the olfactory bulb in a nutrition or energy state‐dependent manner to influence olfactory detection or metabolic sensing.The results of the present study uncover a new function for an olfactory bulb neuron (deep short axon cells, Cajal cells) that could be capable of modifying mitral cell activity through the release of GLP‐1. This might be of relevance for the action of GLP‐1 mimetics now widely used in the treatment of diabetes. Abstract The olfactory system is intricately linked with the endocrine system where it may serve as a detector of the internal metabolic state or energy homeostasis in addition to its classical function as a sensor of external olfactory information. The recent development of transgenic mGLU‐yellow fluorescent protein mice that express a genetic reporter under the control of the preproglucagon reporter suggested the presence of the gut hormone, glucagon‐like peptide (GLP‐1), in deep short axon cells (Cajal cells) of the olfactory bulb and its neuromodulatory effect on mitral cell (MC) first‐order neurons. A MC target for the peptide was determined using GLP‐1 receptor binding assays, immunocytochemistry for the receptor and injection of fluorescence‐labelled GLP‐1 analogue exendin‐4. Using patch clamp recording of olfactory bulb slices in the whole‐cell configuration, we report that GLP‐1 and its

  3. Changes in gut hormone levels and negative energy balance during aerobic exercise in obese young males.

    PubMed

    Ueda, Shin-ya; Yoshikawa, Takahiro; Katsura, Yoshihiro; Usui, Tatsuya; Nakao, Hayato; Fujimoto, Shigeo

    2009-04-01

    We examined whether changes in gut hormone levels due to a single bout of aerobic exercise differ between obese young males and normal controls, and attempted to determine the involvement of hormonal changes during exercise in the regulation of energy balance (EB) in these obese subjects. Seven obese and seven age-matched subjects of normal weight participated in exercise and rest sessions. Subjects consumed a standardized breakfast that was followed by constant cycling exercise at 50% VO(2max) or rest for 60 min. At lunch, a test meal was presented, and energy intake (EI) and relative energy intake (REI) were calculated. Blood samples were obtained at 30 min intervals during both sessions for measurement of glucose, insulin, glucagon, ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise. The areas under the curve (AUC) of the time courses of PYY and GLP-1 levels did not significantly differ between the two groups. In contrast, EI and REI were decreased by exercise in both groups, and energy deficit was significantly larger in obese subjects than in normal controls. The present findings suggest that short-term EB during a single exercise session might be regulated not by increased amounts of these gut hormones per se. PMID:19158129

  4. Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity

    PubMed Central

    Miras, Alexander D.; Scholtz, Samantha; Jackson, Sabrina; Neff, Karl J.; Pénicaud, Luc; Geoghegan, Justin; Chhina, Navpreet; Durighel, Giuliana; Bell, Jimmy D.; Meillon, Sophie; le Roux, Carel W.

    2016-01-01

    Context: Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. Objective: To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. Design: These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. Patients: Two groups, more than 5 months after RYGB for obesity (n = 7–11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. Intervention: Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. Main Outcome Measures: Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. Results: Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. Conclusions: Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food. PMID:26580235

  5. Incretin-based therapies.

    PubMed

    Neumiller, Joshua J

    2015-01-01

    Incretin-based therapies are steadily gaining clinical popularity, with many more products in the developmental pipeline. Current treatment recommendations incorporate GLP-1 RAs and DPP-4 inhibitors as important agents for consideration in the treatment of T2DM owing to their low hypoglycemia risk, ability to address postprandial hyperglycemia (DPP-4 inhibitors and short-acting GLP-1 RAs), and potential for weight reduction (GLP-1 RAs). These properties may likewise prove advantageous in older adults in whom hypoglycemia is particularly undesirable, although older adults may be more prone to the nausea and vomiting associated with GLP-1 RA therapy. Other safety issues for incretin-based therapies, such as pancreatitis, C-cell hyperplasia, and renal failure, should be considered when choosing an appropriate patient to receive such therapies. Ongoing CV outcome studies will further inform the health care community regarding the CV safety of incretin-based therapies. The availability of both short-acting and long-acting GLP-1 RAs currently allows practitioners to consider individualized blood glucose trends and therapeutic needs when choosing an optimal agent. PMID:25456646

  6. Sex differences and hormonal effects on gut microbiota composition in mice

    PubMed Central

    Org, Elin; Mehrabian, Margarete; Parks, Brian W.; Shipkova, Petia; Liu, Xiaoqin; Drake, Thomas A.; Lusis, Aldons J.

    2016-01-01

    ABSTRACT We previously reported quantitation of gut microbiota in a panel of 89 different inbred strains of mice, and we now examine the question of sex differences in microbiota composition. When the total population of 689 mice was examined together, several taxa exhibited significant differences in abundance between sexes but a larger number of differences were observed at the single strain level, suggesting that sex differences can be obscured by host genetics and environmental factors. We also examined a subset of mice on chow and high fat diets and observed sex-by-diet interactions. We further investigated the sex differences using gonadectomized and hormone treated mice from 3 different inbred strains. Principal coordinate analysis with unweighted UniFrac distances revealed very clear effects of gonadectomy and hormone replacement on microbiota composition in all 3 strains. Moreover, bile acid analyses showed gender-specific differences as well as effects of gonodectomy, providing one possible mechanism mediating sex differences in microbiota composition. PMID:27355107

  7. Associations of Circulating Gut Hormone and Adipocytokine Levels with the Spectrum of Gastroesophageal Reflux Disease

    PubMed Central

    Tseng, Ping-Huei; Yang, Wei-Shiung; Liou, Jyh-Ming; Lee, Yi-Chia; Wang, Hsiu-Po; Lin, Jaw-Town; Wu, Ming-Shiang

    2015-01-01

    Objective The pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD. Methods One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett’s esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects. Results All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25th-75th percentile), 80.1 (49.8–108.3) vs. 99.4 (65.8–131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0–120.8) vs. 32.8 (28.7–84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6–9.3) vs. 9.9 (9.6–10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1–9.2) vs. 9.2 (7.1–11.2) μg/ml, p = 0.026] than those without BE. Conclusions Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD

  8. Effect of Alginate on Satiation, Appetite, Gastric Function and Selected Gut Satiety Hormones in Overweight and Obesity

    PubMed Central

    Odunsi, Suwebatu T.; Vázquez Roque, María I.; Camilleri, Michael; Papathanasopoulos, Athanasios; Clark, Matthew M.; Wodrich, Lynne; Lempke, Mary; McKinzie, Sanna; Ryks, Michael; Burton, Duane; Zinsmeister, Alan R.

    2010-01-01

    Lack of control of food intake, excess size and frequency of meals are critical in to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria Digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo-controlled, allocation-concealed study in 48 overweight or obese participants with excluded psychiatric co-morbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting and postprandial gastric volumes (GV), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (3 capsules vs. matching placebo per day, ingested 30 minutes before the main meal). Six capsules were ingested with water 30 minutes before the gastric emptying, gastric volume and satiation tests on days 8–10. There were no treatment group effects on gastric emptying or volumes, gut hormones (ghrelin, CCK, GLP-1, PYY), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment over 10 days has no effect on gastric motor functions, satiation, appetite or gut hormones. These results question the use of short-term alginate treatment for weight loss. PMID:19960001

  9. Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity.

    PubMed

    Odunsi, Suwebatu T; Vázquez-Roque, María I; Camilleri, Michael; Papathanasopoulos, Athanasios; Clark, Matthew M; Wodrich, Lynne; Lempke, Mary; McKinzie, Sanna; Ryks, Michael; Burton, Duane; Zinsmeister, Alan R

    2010-08-01

    Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo-controlled, allocation-concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8-10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short-term alginate treatment for weight loss. PMID:19960001

  10. Anorexigenic effects of miglitol in concert with the alterations of gut hormone secretion and gastric emptying in healthy subjects.

    PubMed

    Kaku, H; Tajiri, Y; Yamada, K

    2012-04-01

    Although the α-glucosidase inhibitor miglitol (MG) has been reported to have anorexigenic effects, the mechanism remains to be elucidated. The objective of this study was to explore the effects of MG on appetite in relation to concomitant changes in postprandial gut hormone levels. This randomized open-label crossover study included 20 healthy volunteers. The effects of 50 mg MG on glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin levels were assessed in conjunction with a simultaneous determination of appetite scores using visual analogue scales (VAS) over 3 h after the ingestion of a 592 kcal test cookie. Additionally, the gastric emptying rate (GER) was measured using breath ¹³CO₂ appearance in 10 subjects. 12 subjects were administered 50 mg MG thrice a day for 1 week, and alterations of the gut hormone levels and the VAS scores for appetite were evaluated. MG pre-administration resulted in a significant enhancement of GLP-1 and PYY responses induced by the cookie ingestion. Following MG administration, ghrelin level declined at 1 h, with a persistent suppression during the postprandial phase in contrast to the restoration to the basal level without MG. Furthermore, MG pre-administration suppressed appetite and maintained satiety evaluated using a VAS rating with concomitant inhibition of GER after cookie ingestion. One-week administration of MG did not influence either gut hormone levels before a meal or VAS rating during a whole day. These observations suggest that MG exerts an anorexigenic effects with concomitant alterations of gut hormone secretions and gastric emptying after meal ingestion. PMID:22351480

  11. Medicinal Chemistry and Applications of Incretins and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes Mellitus

    PubMed Central

    Lotfy, Mohamed; Singh, Jaipaul; Kalász, Huba; Tekes, Kornelia; Adeghate, Ernest

    2011-01-01

    Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase. PMID:21966329

  12. New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders

    PubMed Central

    Irwin, Nigel; Flatt, Peter R

    2015-01-01

    The applicability of stable gut hormones for the treatment of obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained glucose-lowering actions, plus evidence that these peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), oxyntomodulin (OXM) and cholecystokinin (CCK) for obesity-related diabetes. Stable GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of antidiabetic drugs. Moreover, recent studies have shown improved therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination therapy or use of dual/triple agonist peptides. However, timing and composition of injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of incretin based drugs for treatment of prediabetes. Finally, the unanticipated utility of stable gut peptides as effective treatments for complications of diabetes, bone disorders, cognitive impairment and cardiovascular dysfunction is considered. PMID:26557956

  13. Intestinal organoids for assessing nutrient transport, sensing and incretin secretion

    PubMed Central

    Zietek, Tamara; Rath, Eva; Haller, Dirk; Daniel, Hannelore

    2015-01-01

    Intestinal nutrient transport and sensing are of emerging interest in research on obesity and diabetes and as drug targets. Appropriate in vitro models are lacking that allow both, studies on transport processes as well as sensing and subsequent incretin hormone secretion including intracellular signaling. We here demonstrate that murine small-intestinal organoids are the first in vitro model system enabling concurrent investigations of nutrient and drug transport, sensing and incretin hormone secretion as well as fluorescent live-cell imaging of intracellular signaling processes. By generating organoid cultures from wild type mice and animals lacking different nutrient transporters, we show that organoids preserve the main phenotypic features and functional characteristics of the intestine. This turns them into the best in vitro model currently available and opens new avenues for basic as well as medical research. PMID:26582215

  14. Incretin manipulation in diabetes management

    PubMed Central

    Pappachan, Joseph M; Raveendran, AV; Sriraman, Rajagopalan

    2015-01-01

    Incretin-based therapies have revolutionized the medical management of type 2 diabetes mellitus (T2DM) in the 21st century. Glucagon-like peptide-1 (GLP-1) suppresses appetite and gastric motility, and has trophic effects on pancreas, cardio-protective and renal effects. GLP-1 analogues and dipeptidyl peptidase-4 inhibitors form the incretin-based therapies. Significant reduction of hemoglobin A1c when used as monotherapy and in combination regimens, favorable effects on body weight, and low risk of hypoglycemia are their unique therapeutic benefits. Their safety and tolerability are comparable to other anti-diabetic medications. Concern about elevated risk of pancreatitis has been discarded by two recent meta-analyses. This article discusses the therapeutic manipulation of incretin system for the management of T2DM. PMID:26131320

  15. Incretin manipulation in diabetes management.

    PubMed

    Pappachan, Joseph M; Raveendran, A V; Sriraman, Rajagopalan

    2015-06-25

    Incretin-based therapies have revolutionized the medical management of type 2 diabetes mellitus (T2DM) in the 21(st) century. Glucagon-like peptide-1 (GLP-1) suppresses appetite and gastric motility, and has trophic effects on pancreas, cardio-protective and renal effects. GLP-1 analogues and dipeptidyl peptidase-4 inhibitors form the incretin-based therapies. Significant reduction of hemoglobin A1c when used as monotherapy and in combination regimens, favorable effects on body weight, and low risk of hypoglycemia are their unique therapeutic benefits. Their safety and tolerability are comparable to other anti-diabetic medications. Concern about elevated risk of pancreatitis has been discarded by two recent meta-analyses. This article discusses the therapeutic manipulation of incretin system for the management of T2DM. PMID:26131320

  16. The Effect of Normobaric Hypoxic Confinement on Metabolism, Gut Hormones, and Body Composition.

    PubMed

    Mekjavic, Igor B; Amon, Mojca; Kölegård, Roger; Kounalakis, Stylianos N; Simpson, Liz; Eiken, Ola; Keramidas, Michail E; Macdonald, Ian A

    2016-01-01

    To assess the effect of normobaric hypoxia on metabolism, gut hormones, and body composition, 11 normal weight, aerobically trained (O2peak: 60.6 ± 9.5 ml·kg(-1)·min(-1)) men (73.0 ± 7.7 kg; 23.7 ± 4.0 years, BMI 22.2 ± 2.4 kg·m(-2)) were confined to a normobaric (altitude ≃ 940 m) normoxic (NORMOXIA; PIO2 ≃ 133.2 mmHg) or normobaric hypoxic (HYPOXIA; PIO was reduced from 105.6 to 97.7 mmHg over 10 days) environment for 10 days in a randomized cross-over design. The wash-out period between confinements was 3 weeks. During each 10-day period, subjects avoided strenuous physical activity and were under continuous nutritional control. Before, and at the end of each exposure, subjects completed a meal tolerance test (MTT), during which blood glucose, insulin, GLP-1, ghrelin, peptide-YY, adrenaline, noradrenaline, leptin, and gastro-intestinal blood flow and appetite sensations were measured. There was no significant change in body weight in either of the confinements (NORMOXIA: -0.7 ± 0.2 kg; HYPOXIA: -0.9 ± 0.2 kg), but a significant increase in fat mass in NORMOXIA (0.23 ± 0.45 kg), but not in HYPOXIA (0.08 ± 0.08 kg). HYPOXIA confinement increased fasting noradrenaline and decreased energy intake, the latter most likely associated with increased fasting leptin. The majority of all other measured variables/responses were similar in NORMOXIA and HYPOXIA. To conclude, normobaric hypoxic confinement without exercise training results in negative energy balance due to primarily reduced energy intake. PMID:27313541

  17. The Effect of Normobaric Hypoxic Confinement on Metabolism, Gut Hormones, and Body Composition

    PubMed Central

    Mekjavic, Igor B.; Amon, Mojca; Kölegård, Roger; Kounalakis, Stylianos N.; Simpson, Liz; Eiken, Ola; Keramidas, Michail E.; Macdonald, Ian A.

    2016-01-01

    To assess the effect of normobaric hypoxia on metabolism, gut hormones, and body composition, 11 normal weight, aerobically trained (O2peak: 60.6 ± 9.5 ml·kg−1·min−1) men (73.0 ± 7.7 kg; 23.7 ± 4.0 years, BMI 22.2 ± 2.4 kg·m−2) were confined to a normobaric (altitude ≃ 940 m) normoxic (NORMOXIA; PIO2 ≃ 133.2 mmHg) or normobaric hypoxic (HYPOXIA; PIO was reduced from 105.6 to 97.7 mmHg over 10 days) environment for 10 days in a randomized cross-over design. The wash-out period between confinements was 3 weeks. During each 10-day period, subjects avoided strenuous physical activity and were under continuous nutritional control. Before, and at the end of each exposure, subjects completed a meal tolerance test (MTT), during which blood glucose, insulin, GLP-1, ghrelin, peptide-YY, adrenaline, noradrenaline, leptin, and gastro-intestinal blood flow and appetite sensations were measured. There was no significant change in body weight in either of the confinements (NORMOXIA: −0.7 ± 0.2 kg; HYPOXIA: −0.9 ± 0.2 kg), but a significant increase in fat mass in NORMOXIA (0.23 ± 0.45 kg), but not in HYPOXIA (0.08 ± 0.08 kg). HYPOXIA confinement increased fasting noradrenaline and decreased energy intake, the latter most likely associated with increased fasting leptin. The majority of all other measured variables/responses were similar in NORMOXIA and HYPOXIA. To conclude, normobaric hypoxic confinement without exercise training results in negative energy balance due to primarily reduced energy intake. PMID:27313541

  18. The effect of α- or β-casein addition to waxy maize starch on postprandial levels of glucose, insulin, and incretin hormones in pigs as a model for humans

    PubMed Central

    Kett, Anthony P.; Bruen, Christine M.; O'Halloran, Fiona; Chaurin, Valérie; Lawlor, Peadar G.; O'Mahony, James A.; Giblin, Linda; Fenelon, Mark A.

    2012-01-01

    Background Starch is a main source of glucose and energy in the human diet. The extent to which it is digested in the gastrointestinal tract plays a major role in variations in postprandial blood glucose levels. Interactions with other biopolymers, such as dairy proteins, during processing can influence both the duration and extent of this postprandial surge. Objective To evaluate the effect of the addition of bovine α- or β-casein to waxy maize starch on changes in postprandial blood glucose, insulin, and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)] in 30 kg pigs used as an animal model for humans. Design Gelatinised starch, starch gelatinised with α-casein, and starch gelatinised with β-casein were orally administered to trained pigs (n = 8) at a level of 60 g of available carbohydrate. Pre- and postprandial glucose measurements were taken every 15 min for the first hour and every 30 min thereafter up to 180 min. Insulin, GIP, and GLP-1 levels were measured in plasma samples up to 90 min postprandial. Results Starch gelatinised with α-casein had a significantly (p < 0.05) lower peak viscosity on pasting and resulted in significantly lower glucose release at 15, 30, and 90 min postprandial compared to starch gelatinised with β-casein. During the first 45-min postprandial, the area under the glucose curve (AUC) for starch gelatinised with α-casein was significantly (p < 0.05) lower than that for starch gelatinised with β-casein. There was also a significant (p < 0.05) difference at T30 in GIP levels in response to the control compared to starch gelatinised with α- or β-casein. Significant (p < 0.05) increases in several free amino acid concentrations were observed on ingestion of either α- or β-casein gelatinised with starch at 30 and 90 min postprandial compared to starch alone. In addition, plasma levels of six individual amino acids were increased on ingestion of starch gelatinised with

  19. Dose-Dependent Effects of a Soluble Dietary Fibre (Pectin) on Food Intake, Adiposity, Gut Hypertrophy and Gut Satiety Hormone Secretion in Rats

    PubMed Central

    Adam, Clare L.; Williams, Patricia A.; Garden, Karen E.; Thomson, Lynn M.; Ross, Alexander W.

    2015-01-01

    Soluble fermentable dietary fibre elicits gut adaptations, increases satiety and potentially offers a natural sustainable means of body weight regulation. Here we aimed to quantify physiological responses to graded intakes of a specific dietary fibre (pectin) in an animal model. Four isocaloric semi-purified diets containing 0, 3.3%, 6.7% or 10% w/w apple pectin were offered ad libitum for 8 or 28 days to young adult male rats (n = 8/group). Measurements were made of voluntary food intake, body weight, initial and final body composition by magnetic resonance imaging, final gut regional weights and histology, and final plasma satiety hormone concentrations. In both 8- and 28-day cohorts, dietary pectin inclusion rate was negatively correlated with food intake, body weight gain and the change in body fat mass, with no effect on lean mass gain. In both cohorts, pectin had no effect on stomach weight but pectin inclusion rate was positively correlated with weights and lengths of small intestine and caecum, jejunum villus height and crypt depth, ileum crypt depth, and plasma total glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) concentrations, and at 8 days was correlated with weight and length of colon and with caecal mucosal depth. Therefore, the gut’s morphological and endocrine adaptations were dose-dependent, occurred within 8 days and were largely sustained for 28 days during continued dietary intervention. Increasing amounts of the soluble fermentable fibre pectin in the diet proportionately decreased food intake, body weight gain and body fat content, associated with proportionately increased satiety hormones GLP-1 and PYY and intestinal hypertrophy, supporting a role for soluble dietary fibre-induced satiety in healthy body weight regulation. PMID:25602757

  20. Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide Fragments of the Gut-Derived Hormone Xenin

    PubMed Central

    Martin, Christine M.; Parthsarathy, Vadivel; Hasib, Annie; Ng, Ming T.; McClean, Stephen; Flatt, Peter R.; Gault, Victor A.; Irwin, Nigel

    2016-01-01

    Xenin is a peptide that is co-secreted with the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), from intestinal K-cells in response to feeding. Studies demonstrate that xenin has appetite suppressive effects and modulates glucose-induced insulin secretion. The present study was undertaken to determine the bioactivity and antidiabetic properties of two C-terminal fragment xenin peptides, namely xenin 18–25 and xenin 18–25 Gln. In BRIN-BD11 cells, both xenin fragment peptides concentration-dependently stimulated insulin secretion, with similar efficacy as the parent peptide. Neither fragment peptide had any effect on acute feeding behaviour at elevated doses of 500 nmol/kg bw. When administered together with glucose to normal mice at 25 nmol/kg bw, the overall insulin secretory effect was significantly enhanced in both xenin 18–25 and xenin 18–25 Gln treated mice, with better moderation of blood glucose levels. Twice daily administration of xenin 18–25 or xenin 18–25 Gln for 21 days in high fat fed mice did not affect energy intake, body weight, circulating blood glucose or body fat stores. However, circulating plasma insulin concentrations had a tendency to be elevated, particularly in xenin 18–25 Gln mice. Both treatment regimens significantly improved insulin sensitivity by the end of the treatment period. In addition, sustained treatment with xenin 18–25 Gln significantly reduced the overall glycaemic excursion and augmented the insulinotropic response to an exogenous glucose challenge on day 21. In harmony with this, GIP-mediated glucose-lowering and insulin-releasing effects were substantially improved by twice daily xenin 18–25 Gln treatment. Overall, these data provide evidence that C-terminal octapeptide fragments of xenin, such as xenin 18–25 Gln, have potential therapeutic utility for type 2 diabetes. PMID:27032106

  1. Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion

    PubMed Central

    2016-01-01

    Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281). PMID:26839476

  2. Extrapancreatic effects of incretin hormones: evidence for weight-independent changes in morphological aspects and oxidative status in insulin-sensitive organs of the obese nondiabetic Zucker rat (ZFR).

    PubMed

    Colin, Ides M; Colin, Henri; Dufour, Ines; Gielen, Charles-Edouard; Many, Marie-Christine; Saey, Jean; Knoops, Bernard; Gérard, Anne-Catherine

    2016-08-01

    Incretin-based therapies are widely used to treat type 2 diabetes. Although hypoglycemic actions of incretins are mostly due to their insulinotropic/glucagonostatic effects, they may also influence extrapancreatic metabolism. We administered exendin-4 (Ex-4), a long-acting glucagon-like peptide receptor agonist, at low dose (0.1 nmol/kg/day) for a short period (10 days), in obese nondiabetic fa/fa Zucker rats (ZFRs). Ex-4-treated ZFRs were compared to vehicle (saline)-treated ZFRs and vehicle- and Ex-4-treated lean rats (LRs). Blood glucose levels were measured at days 0, 9, and 10. Ingested food and animal weight were recorded daily. On the day of sacrifice (d10), blood was sampled along with liver, epididymal, subcutaneous, brown adipose, and skeletal muscle tissues from animals fasted for 24 h. Plasma insulin and blood glucose levels, food intake, and body and epididymal fat weight were unchanged, but gross morphological changes were observed in insulin-sensitive tissues. The average size of hepatocytes was significantly lower in Ex-4-treated ZFRs, associated with decreased number and size of lipid droplets and 4-hydroxy-2-nonenal (HNE) staining, a marker of oxidative stress (OS). Myocytes, which were smaller in ZFRs than in LRs, were significantly enlarged and depleted of lipid droplets in Ex-4-treated ZFRs. Weak HNE staining was increased by Ex-4. A similar observation was made in brown adipose tissue, whereas the elevated HNE staining observed in epididymal adipocytes of ZFRs, suggestive of strong OS, was decreased by Ex-4. These results suggest that incretins by acting on OS in insulin-sensitive tissues may contribute to weight-independent improvement in insulin sensitivity. PMID:27511983

  3. Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.

    PubMed

    Nauck, M

    2016-03-01

    Over the last few years, incretin-based therapies have emerged as important agents in the treatment of type 2 diabetes (T2D). These agents exert their effect via the incretin system, specifically targeting the receptor for the incretin hormone glucagon-like peptide 1 (GLP-1), which is partly responsible for augmenting glucose-dependent insulin secretion in response to nutrient intake (the 'incretin effect'). In patients with T2D, pharmacological doses/concentrations of GLP-1 can compensate for the inability of diabetic β cells to respond to the main incretin hormone glucose-dependent insulinotropic polypeptide, and this is therefore a suitable parent compound for incretin-based glucose-lowering medications. Two classes of incretin-based therapies are available: GLP-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1RAs promote GLP-1 receptor (GLP-1R) signalling by providing GLP-1R stimulation through 'incretin mimetics' circulating at pharmacological concentrations, whereas DPP-4 inhibitors prevent the degradation of endogenously released GLP-1. Both agents produce reductions in plasma glucose and, as a result of their glucose-dependent mode of action, this is associated with low rates of hypoglycaemia; however, there are distinct modes of action resulting in differing efficacy and tolerability profiles. Furthermore, as their actions are not restricted to stimulating insulin secretion, these agents have also been associated with additional non-glycaemic benefits such as weight loss, improvements in β-cell function and cardiovascular risk markers. These attributes have made incretin therapies attractive treatments for the management of T2D and have presented physicians with an opportunity to tailor treatment plans. This review endeavours to outline the commonalities and differences among incretin-based therapies and to provide guidance regarding agents most suitable for treating T2D in individual patients. PMID:26489970

  4. Anti-incretin, Anti-proliferative Action of Dopamine on β-Cells

    PubMed Central

    Segal, Ann Marie; Alvarez-Perez, Juan Carlos; Garcia-Ocaña, Adolfo; Harris, Paul E.

    2015-01-01

    Human islet β-cells exploit an autocrine dopamine (DA)-mediated inhibitory circuit to regulate insulin secretion. β-Cells also express the DA active transporter and the large neutral amino acid transporter heterodimer enabling them to import circulating DA or its biosynthetic precursor, L-3,4-dihydroxyphenylalanine (L-DOPA). The capacity to import DA or L-DOPA from the extracellular space possibly indicates that DA may be an endocrine signal as well. In humans, a mixed meal stimulus is accompanied by contemporary serum excursions of incretins, DA and L-DOPA, suggesting that DA may act as an anti-incretin as postulated by the foregut hypothesis proposed to explain the early effects of bariatric surgery on type 2 diabetes. In this report, we take a translational step backwards and characterize the kinetics of plasma DA and incretin production after a mixed meal challenge in a rat model and study the integration of incretin and DA signaling at the biochemical level in a rodent β-cell line and islets. We found that there are similar excursions of incretins and DA in rats, as those reported in humans, after a mixed meal challenge and that DA counters incretin enhanced glucose-stimulated insulin secretion and intracellular signaling at multiple points from dampening calcium fluxes to inhibiting proliferation as well as apoptosis. Our data suggest that DA is an important regulator of insulin secretion and may represent 1 axis of a gut level circuit of glucose and β-cell mass homeostasis. PMID:25751312

  5. An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass

    PubMed Central

    Chon, Suk

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans. PMID:27126881

  6. Pancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice

    PubMed Central

    Lamont, Benjamin J.; Li, Yazhou; Kwan, Edwin; Brown, Theodore J.; Gaisano, Herbert; Drucker, Daniel J.

    2011-01-01

    Glucagon-like peptide-1 (GLP-1) circulates at low levels and acts as an incretin hormone, potentiating glucose-dependent insulin secretion from islet β cells. GLP-1 also modulates gastric emptying and engages neural circuits in the portal region and CNS that contribute to GLP-1 receptor–dependent (GLP-1R–dependent) regulation of glucose homeostasis. To elucidate the importance of pancreatic GLP-1R signaling for glucose homeostasis, we generated transgenic mice that expressed the human GLP-1R in islets and pancreatic ductal cells (Pdx1-hGLP1R:Glp1r–/– mice). Transgene expression restored GLP-1R–dependent stimulation of cAMP and Akt phosphorylation in isolated islets, conferred GLP-1R–dependent stimulation of β cell proliferation, and was sufficient for restoration of GLP-1–stimulated insulin secretion in perifused islets. Systemic GLP-1R activation with the GLP-1R agonist exendin-4 had no effect on food intake, hindbrain c-fos expression, or gastric emptying but improved glucose tolerance and stimulated insulin secretion in Pdx1-hGLP1R:Glp1r–/– mice. i.c.v. GLP-1R blockade with the antagonist exendin(9–39) impaired glucose tolerance in WT mice but had no effect in Pdx1-hGLP1R:Glp1r–/– mice. Nevertheless, transgenic expression of the pancreatic GLP-1R was sufficient to normalize both oral and i.p. glucose tolerance in Glp1r–/– mice. These findings illustrate that low levels of endogenous GLP-1 secreted from gut endocrine cells are capable of augmenting glucoregulatory activity via pancreatic GLP-1Rs independent of communication with neural pathways. PMID:22182839

  7. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  8. Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?

    PubMed

    Sourris, Karly C; Yao, Henry; Jerums, George; Cooper, Mark E; Ekinci, Elif I; Coughlan, Melinda T

    2016-01-01

    Diabetic nephropathy is the major cause of end-stage renal disease in Western societies. To date, interruption of the Renin-Angiotensin System is the most effective intervention for diabetic nephropathy, however these agents only slow progression of the disease. Thus, there is a major unmet need for new therapeutic targets. Aberrant activation of the receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic nephropathy via binding to a variety of ligands and inciting reactive oxygen species (ROS) production, inflammation and fibrosis. In recent years there have been considerable efforts in the development of effective RAGE antagonists, however, direct RAGE targeting may be problematic. Glucagon like peptide-1 (GLP-1) is an incretin hormone released by the L-cells of the small intestine to mediate glucose-dependent insulin release from pancreatic islets. The incretin-based therapies, GLP-1 receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors, are novel glucose-lowering agents used in type 2 diabetes. However, the extra pancreatic functions of GLP-1 have gained attention, including putative anti-apoptotic and anti-inflammatory properties. In rodent models of diabetes, incretin-based therapies are renoprotective. Interestingly, GLP-1 has been shown to interfere with the signalling and expression of RAGE. The current review aims to give an overview of the interactions between the RAGE and incretin pathways and to discuss the utility of targeting the GLP-1/incretin pathway in DN. It is possible that indirect targeting of RAGE through GLP-1 agonism will be of clinical benefit to patients with diabetic nephropathy. PMID:26201485

  9. Comparative Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Glucose Homeostasis and Incretin Hormones in Obese Type 2 Diabetic Patients: A One-Year Prospective Study.

    PubMed

    Nosso, G; Griffo, E; Cotugno, M; Saldalamacchia, G; Lupoli, R; Pacini, G; Riccardi, G; Angrisani, L; Capaldo, B

    2016-05-01

    The aim of the work was to compare the hormonal and the metabolic mechanisms involved in weight loss and remission of T2DM one year after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in morbidly obese type 2 diabetic (T2DM) patients. Insulin sensitivity, insulin secretion, and the gastrointestinal (GI) hormone response to a mixed meal test (MMT) were evaluated before and one year after BS (14 RYGB and 19 VSG). RYGB and VSG groups had similar characteristics at baseline. Weight loss at one year was similar in the 2 groups (ΔBMI%: - 32±10 and - 30±7%, p=0.546). Insulin sensitivity and insulin secretion improved similarly after either procedures with a similar rate in T2DM remission (86% in RYGB and 76% in VSG). Meal-stimulated GLP-1 levels increased after both procedures reaching significantly higher levels after RYGB (p=0.0001). GIP response to MMT decreased to a similar extent after the 2 interventions (p=0.977). Both fasting and post-meal ghrelin concentrations were markedly suppressed after VSG and significantly lower than RYGB (p=0.013 to p=0.035). The improvement of insulin sensitivity and beta-cell function was significantly associated with weight loss (p=0.014 to p=0.035), while no relation was found with the changes in GI hormones. In conclusion, in morbidly obese T2DM patients, RYGB and VSG result in similar improvements of the glucose status in the face of different GI hormonal pattern. Weight loss is the key determinant of diabetes remission one year after surgery. PMID:26788926

  10. Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects.

    PubMed

    Nilsson, Anne C; Johansson-Boll, Elin V; Björck, Inger M E

    2015-09-28

    Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota-mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56%) and postprandially (p-glucagon-like peptide-2; 13% and p-peptide YY; 18%). Breath H₂ excretion and fasting serum (s) SCFA concentrations were increased (363 and 18%, respectively), and b-glucose (22%) and s-insulin responses (17%) were decreased after BB intervention. Insulin sensitivity index (ISI(composite)) was also improved (25%) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome. PMID:26259632

  11. Hormones

    MedlinePlus

    ... the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal ...

  12. Incretin agents in type 2 diabetes

    PubMed Central

    Ross, Stuart A.; Ekoé, Jean-Marie

    2010-01-01

    Abstract OBJECTIVE To evaluate the emerging classes of antihyperglycemic agents that target the incretin pathway, including their therapeutic efficacy and side effect profiles, in order to help identify their place among the treatment options for patients with type 2 diabetes. QUALITY OF EVIDENCE MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched. Most evidence is level I and II. MAIN MESSAGE Two classes of incretin agents are currently available: glucagonlike peptide 1 (GLP1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, both of which lower hyperglycemia considerably without increasing the risk of hypoglycemia. The GLP1 receptor agonists have a greater effect on patients’ glycated hemoglobin A1c levels and cause sustained weight loss, whereas the DPP4 inhibitors are weight-neutral. CONCLUSION The GLP1 and DPP4 incretin agents, promising and versatile antihyperglycemic agents, are finding their way into the therapeutic algorithm for treating type 2 diabetes. They can be used in patients not adequately controlled by metformin monotherapy or as initial therapy in those for whom metformin is contraindicated. PMID:20631270

  13. Beyond Glycemic Control in Diabetes Mellitus: Effects of Incretin-Based Therapies on Bone Metabolism

    PubMed Central

    Ceccarelli, Elena; Guarino, Elisa G.; Merlotti, Daniela; Patti, Aurora; Gennari, Luigi; Nuti, Ranuccio; Dotta, Francesco

    2013-01-01

    Diabetes mellitus (DM) and osteoporosis (OP) are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM) and in type 2 (T2DM) diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g., thiazolidinediones, insulin) may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e., GLP-1 receptor agonists and DPP-4 inhibitors) is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells. Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients. PMID:23785355

  14. Gut chemosensing mechanisms

    PubMed Central

    Psichas, Arianna; Reimann, Frank; Gribble, Fiona M.

    2015-01-01

    The enteroendocrine system is the primary sensor of ingested nutrients and is responsible for secreting an array of gut hormones, which modulate multiple physiological responses including gastrointestinal motility and secretion, glucose homeostasis, and appetite. This Review provides an up-to-date synopsis of the molecular mechanisms underlying enteroendocrine nutrient sensing and highlights our current understanding of the neuro-hormonal regulation of gut hormone secretion, including the interaction between the enteroendocrine system and the enteric nervous system. It is hoped that a deeper understanding of how these systems collectively regulate postprandial physiology will further facilitate the development of novel therapeutic strategies. PMID:25664852

  15. Therapeutic Applications of Incretin Mimetics for Metabolic Diseases: Preclinical Studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exenatide (exendin-4) is an incretin mimetic peptide that shares several glucoregulatory actions with the endogenous incretin GLP-1. In addition to its actions on glucose control, exenatide produces effects to reduce food intake and body weight in all species studied. GLP-1 and exenatide have also b...

  16. Differential impacts of juvenile hormone, soldier head extract and alternate caste phenotypes on host and symbiont transcriptome composition in the gut of the termite Reticulitermes flavipes

    PubMed Central

    2013-01-01

    Background Termites are highly eusocial insects and show a division of labor whereby morphologically distinct individuals specialize in distinct tasks. In the lower termite Reticulitermes flavipes (Rhinotermitidae), non-reproducing individuals form the worker and soldier castes, which specialize in helping (e.g., brood care, cleaning, foraging) and defense behaviors, respectively. Workers are totipotent juveniles that can either undergo status quo molts or develop into soldiers or neotenic reproductives. This caste differentiation can be regulated by juvenile hormone (JH) and primer pheromones contained in soldier head extracts (SHE). Here we offered worker termites a cellulose diet treated with JH or SHE for 24-hr, or held them with live soldiers (LS) or live neotenic reproductives (LR). We then determined gene expression profiles of the host termite gut and protozoan symbionts concurrently using custom cDNA oligo-microarrays containing 10,990 individual ESTs. Results JH was the most influential treatment (501 total ESTs affected), followed by LS (24 ESTs), LR (12 ESTs) and SHE treatments (6 ESTs). The majority of JH up- and downregulated ESTs were of host and symbiont origin, respectively; in contrast, SHE, LR and LS treatments had more uniform impacts on host and symbiont gene expression. Repeat “follow-up” bioassays investigating combined JH + SHE impacts in relation to individual JH and SHE treatments on a subset of array-positive genes revealed (i) JH and SHE treatments had opposite impacts on gene expression and (ii) JH + SHE impacts on gene expression were generally intermediate between JH and SHE. Conclusions Our results show that JH impacts hundreds of termite and symbiont genes within 24-hr, strongly suggesting a role for the termite gut in JH-dependent caste determination. Additionally, differential impacts of SHE and LS treatments were observed that are in strong agreement with previous studies that specifically investigated soldier caste

  17. Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.

    PubMed

    Bligh, H Frances J; Godsland, Ian F; Frost, Gary; Hunter, Karl J; Murray, Peter; MacAulay, Katrina; Hyliands, Della; Talbot, Duncan C S; Casey, John; Mulder, Theo P J; Berry, Mark J

    2015-02-28

    There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity. PMID:25661189

  18. Incretin response in Asian type 2 diabetes: Are Indians different?

    PubMed

    Singh, Awadhesh Kumar

    2015-01-01

    Incretin-based therapy has clearly emerged as one of the most sought out strategy in managing type 2 diabetes, primarily because they generally do not causes hypoglycemia and possess weight-neutral or weight losing properties. Efficacy-wise too, these agents, are more or less similar to commonly used drugs metformin and sulfonylureas. Interestingly, some studies recently suggested that glycemic response to these incretin-based therapies could also differ ethnicity-wise. Subsequently, meta-analysis from these studies also suggested that Asians may have better response to these incretin-based therapies. This review will be an attempt to critically analyze those studies available in literature and to address as to why East-Asians and South-Asians may have different incretin response compared to non-Asians. PMID:25593823

  19. Prebiotic Fibre Supplementation In Combination With Metformin Modifies Appetite, Energy Metabolism, And Gut Satiety Hormones In Obese Rats

    NASA Astrophysics Data System (ADS)

    Pyra, Kim Alicia

    The prebiotic fibre, oligofructose (OFS), reduces energy intake and improves glycemic control in rodents and man. Metformin (MT) is a commonly used insulin-sensitizing agent that may limit weight gain in individuals with type 2 diabetes. Our objective was to determine if using OFS as an adjunct to MT therapy (AD) modifies satiety hormone production and metabolism in obese rats. Independently, OFS and MT decreased energy intake, body fat, hepatic triglyceride content, plasma leptin and glucose-dependent insulinotropic peptide (GIP) levels. OFS and AD but not MT rats showed superior glycemic control during an oral glucose tolerance test (OGTT) compared to C. Area under the curve for GIP was lowest in ADThe prebiotic fibre, oligofructose (OFS), reduces energy intake and improves glycemic control in rodents and man. Metformin (MT) is a commonly used insulin-sensitizing agent that may limit weight gain in individuals with type 2 diabetes. Our objective was to determine if using OFS as an adjunct to MT therapy (AD) modifies satiety hormone production and metabolism in obese rats. Independently, OFS and MT decreased energy intake, body fat, hepatic triglyceride content, plasma leptin and glucose-dependent insulinotropic peptide (GIP) levels. OFS and AD but not MT rats showed superior glycemic control during an oral glucose tolerance test (OGTT) compared to C. Area under the curve for GIP was lowest in AD

  20. Snapin mediates incretin action and augments glucose-dependent insulin secretion.

    PubMed

    Song, Woo-Jin; Seshadri, Madhav; Ashraf, Uzair; Mdluli, Thembi; Mondal, Prosenjit; Keil, Meg; Azevedo, Monalisa; Kirschner, Lawrence S; Stratakis, Constantine A; Hussain, Mehboob A

    2011-03-01

    Impaired insulin secretion contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). Treatment with the incretin hormone glucagon-like peptide-1 (GLP-1) potentiates insulin secretion and improves metabolic control in humans with T2DM. GLP-1 receptor-mediated signaling leading to insulin secretion occurs via cyclic AMP stimulated protein kinase A (PKA)- as well as guanine nucleotide exchange factor-mediated pathways. However, how these two pathways integrate and coordinate insulin secretion remains poorly understood. Here we show that these incretin-stimulated pathways converge at the level of snapin, and that PKA-dependent phosphorylation of snapin increases interaction among insulin secretory vesicle-associated proteins, thereby potentiating glucose-stimulated insulin secretion (GSIS). In diabetic islets with impaired GSIS, snapin phosphorylation is reduced, and expression of a snapin mutant, which mimics site-specific phosphorylation, restores GSIS. Thus, snapin is a critical node in GSIS regulation and provides a potential therapeutic target to improve β cell function in T2DM. PMID:21356520

  1. The role of gut peptides in the gut-brain-axis of livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gut peptides are small hormones produced within the gut that are involved in many biological processes including, but not limited to, appetite regulation, mucosal growth, and metabolism regulation. Some peptides, such as cholecystokinin (CCK) and xenin-25 may affect appetite by altering gut motilit...

  2. Lipoprotein effects of incretin analogs and dipeptidyl peptidase 4 inhibitors

    PubMed Central

    Zhong, Jixin; Maiseyeu, Andrei; Rajagopalan, Sanjay

    2015-01-01

    Elevated post-prandial lipoprotein levels are common in patients with type 2 diabetes. Post-prandial lipoprotein alterations in type 2 diabetics are widely believed to drive inflammation and are considered a major risk factor for cardiovascular disease in diabetic patients. The incretins glucagon like peptide-1 (GLP-1) and glucose insulinotropic peptide (GIP) modulate post-prandial lipoproteins through a multitude of pathways that are independent of insulin and weight loss. Evidence from both animal models and humans seems to suggest an important effect on triglyceride rich lipoproteins (Apo48 containing) with little to no effects on other lipoproteins at least in humans. Dipeptidyl peptidase-4 (DPP4) inhibitors also appear to share these effects suggesting an important role for incretins in these effects. In this review, we will summarize lipid modulating effects of incretin analogs and DPP-4 inhibitors in both animal models and human studies and provide an overview of mechanisms responsible for these effects. PMID:26005496

  3. From organophosphate poisoning to diabetes mellitus: The incretin effect.

    PubMed

    Rathish, D; Agampodi, S B; Jayasumana, M A C S; Siribaddana, S H

    2016-06-01

    Organophosphate (OP) poisoning induced disruption of glucose homeostasis is well established. OP poisoning leads to accumulation of acetylcholine (ACh) due to the inhibition of acetylcholinesterases (AChE). On the other hand the incidence of type 2 diabetes mellitus (T2DM) is shown to rise along with the use of pesticides in Southeast Asia. Attenuation of the 'incretin effect' is seen in T2DM. This effect is regulated by a complex loop of mechanism involving ACh driven muscarinic receptors. We hypothesize that OP poisoning leads to disruption of glucose homeostasis by attenuation of the incretin effect. Inhibition of the Glucagon Like Peptide-1 (GLP-1) secretion is our main focus of interest. Positive finding of the hypothesis will open possibility of using incretin based treatment modalities to treat or prevent acute OP induced disruption of glucose homeostasis. PMID:27142144

  4. Optical Control of Insulin Secretion Using an Incretin Switch

    PubMed Central

    Broichhagen, Johannes; Podewin, Tom; Meyer‐Berg, Helena; von Ohlen, Yorrick; Johnston, Natalie R.; Jones, Ben J.; Bloom, Stephen R.; Rutter, Guy A.

    2015-01-01

    Abstract Incretin mimetics are set to become a mainstay of type 2 diabetes treatment. By acting on the pancreas and brain, they potentiate insulin secretion and induce weight loss to preserve normoglycemia. Despite this, incretin therapy has been associated with off‐target effects, including nausea and gastrointestinal disturbance. A novel photoswitchable incretin mimetic based upon the specific glucagon‐like peptide‐1 receptor (GLP‐1R) agonist liraglutide was designed, synthesized, and tested. This peptidic compound, termed LirAzo, possesses an azobenzene photoresponsive element, affording isomer‐biased GLP‐1R signaling as a result of differential activation of second messenger pathways in response to light. While the trans isomer primarily engages calcium influx, the cis isomer favors cAMP generation. LirAzo thus allows optical control of insulin secretion and cell survival. PMID:26585495

  5. Obesity and the gut microbiota.

    PubMed

    Flint, Harry J

    2011-11-01

    Gut microorganisms have the potential to influence weight gain and fat deposition through a variety of mechanisms. One factor is the ability of microorganisms in the large intestine to release energy by fermenting otherwise indigestible components of the diet ("energy harvest"). This energy becomes available to the host indirectly through the absorption of microbially produced short-chain fatty acids. Energy recovery from fiber will be largely determined by dietary intake and gut transit, but can also depend on the makeup of the gut microbiota. The species composition of the gut microbiota changes with diet composition, as has been shown in studies with obese individuals after reduced carbohydrate weight loss diets, or diets containing different nondigestible carbohydrates. There is conflicting evidence, however, on the extent to which gut microbiota composition differs between obese and nonobese humans. In contrast, there is increasing evidence to suggest that gut microorganisms and their metabolic products can influence gut hormones, inflammation, and gut motility. Any changes in gut microbiota composition that influence energy expenditure, satiety, and food intake have the potential to alter weight gain and weight loss, but a better understanding of the impact of different members of the gut microbial community upon host physiology is needed to establish these relationships. PMID:21992951

  6. Manipulation of starch bioaccessibility in wheat endosperm to regulate starch digestion, postprandial glycemia, insulinemia, and gut hormone responses: a randomized controlled trial in healthy ileostomy participants12

    PubMed Central

    Edwards, Cathrina H; Grundy, Myriam ML; Grassby, Terri; Vasilopoulou, Dafni; Frost, Gary S; Butterworth, Peter J; Berry, Sarah EE; Sanderson, Jeremy; Ellis, Peter R

    2015-01-01

    Background: Cereal crops, particularly wheat, are a major dietary source of starch, and the bioaccessibility of starch has implications for postprandial glycemia. The structure and properties of plant foods have been identified as critical factors in influencing nutrient bioaccessibility; however, the physical and biochemical disassembly of cereal food during digestion has not been widely studied. Objectives: The aims of this study were to compare the effects of 2 porridge meals prepared from wheat endosperm with different degrees of starch bioaccessibility on postprandial metabolism (e.g., glycemia) and to gain insight into the structural and biochemical breakdown of the test meals during gastroileal transit. Design: A randomized crossover trial in 9 healthy ileostomy participants was designed to compare the effects of 55 g starch, provided as coarse (2-mm particles) or smooth (<0.2-mm particles) wheat porridge, on postprandial changes in blood glucose, insulin, C-peptide, lipids, and gut hormones and on the resistant starch (RS) content of ileal effluent. Undigested food in the ileal output was examined microscopically to identify cell walls and encapsulated starch. Results: Blood glucose, insulin, C-peptide, and glucose-dependent insulinotropic polypeptide concentrations were significantly lower (i.e., 33%, 43%, 40%, and 50% lower 120-min incremental AUC, respectively) after consumption of the coarse porridge than after the smooth porridge (P < 0.01). In vitro, starch digestion was slower in the coarse porridge than in the smooth porridge (33% less starch digested at 90 min, P < 0.05, paired t test). In vivo, the structural integrity of coarse particles (∼2 mm) of wheat endosperm was retained during gastroileal transit. Microscopic examination revealed a progressive loss of starch from the periphery toward the particle core. The structure of the test meal had no effect on the amount or pattern of RS output. Conclusion: The structural integrity of wheat

  7. Gut feeling is electric

    NASA Astrophysics Data System (ADS)

    Familoni, Jide

    2011-06-01

    Although "gut feeling" is a cliché in English parlance, there are neuro-physiological basis for registration of emotions in the gut. Control of the gastro-intestinal (GI) tract is by an integration of neuro-hormonal factors from the local myogenic to the central nervous system. Gastric contractile activity, which is responsible for the motor properties of the stomach, is regulated by this integrated complex. Signatures of the activity include gastric electrical activity (GEA) and bowel sounds. GEA has two distinct components: a high-frequency spike activity or post depolarization potential termed the electrical response activity superimposed on a lower frequency, rhythmic depolarization termed the control activity. These signatures are measured in the clinic with contact sensors and well understood for diagnosis of gut dysmotility. Can these signatures be measured at standoff and employed for purposes of biometrics, malintent and wellness assessment?

  8. Gastrointestinal hormones regulating appetite.

    PubMed

    Chaudhri, Owais; Small, Caroline; Bloom, Steve

    2006-07-29

    The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood-brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the

  9. Targeting Incretins in Type 2 Diabetes: Role of GLP-1 Receptor Agonists and DPP-4 Inhibitors

    PubMed Central

    Pratley, Richard E.; Gilbert, Matthew

    2008-01-01

    Until recently, the pathogenesis of type 2 diabetes mellitus (T2DM) has been conceptualized in terms of the predominant defects in insulin secretion and insulin action. It is now recognized that abnormalities in other hormones also contribute to the development of hyperglycemia. For example, the incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), is attenuated in T2DM. Intravenous administration of GLP-1 ameliorates hyperglycemia in patients with T2DM, but an extremely short half-life limits its utility as a therapeutic agent. Strategies to leverage the beneficial effects of GLP-1 include GLP-1 receptor agonists or analogs or dipeptidyl peptidase-4 (DPP-4) inhibitors—agents that act by slowing the inactivation of endogenous GLP-1 and GIP. The GLP-1 agonist exenatide has been shown to improve HbA1c and decrease body weight. However, exenatide is limited by its relatively short pharmacologic half-life, various gastrointestinal (GI) side effects, and the development of antibodies. Studies of a long-acting exenatide formulation suggest that it has improved efficacy and also promotes weight loss. Another prospect is liraglutide, a once-daily human GLP-1 analog. In phase 2 studies, liraglutide lowered HbA1c by up to 1.7% and weight by approximately 3 kg, with apparently fewer GI side effects than exenatide. DPP-4 inhibitors such as sitagliptin and vildagliptin result in clinically significant reductions in HbA1c, and are weight neutral with few GI side effects. This review will provide an overview of current and emerging agents that augment the incretin system with a focus on the role of GLP-1 receptor agonists and DPP-4 inhibitors. PMID:18795210

  10. The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

    PubMed

    Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

    2016-01-01

    With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. PMID:26461922

  11. Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis.

    PubMed

    Prévost, Gaëtan; Jeandel, Lydie; Arabo, Arnaud; Coëffier, Moïse; El Ouahli, Mariama; Picot, Marie; Alexandre, David; Gobet, Françoise; Leprince, Jérôme; Berrahmoune, Hind; Déchelotte, Pierre; Malagon, Maria; Bonner, Caroline; Kerr-Conte, Julie; Chigr, Fatiha; Lefebvre, Hervé; Anouar, Youssef; Chartrel, Nicolas

    2015-08-01

    26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a high-fat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic β-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis. PMID:25858563

  12. The role of Gut Microbiota in the development of obesity and Diabetes.

    PubMed

    Baothman, Othman A; Zamzami, Mazin A; Taher, Ibrahim; Abubaker, Jehad; Abu-Farha, Mohamed

    2016-01-01

    Obesity and its associated complications like type 2 diabetes (T2D) are reaching epidemic stages. Increased food intake and lack of exercise are two main contributing factors. Recent work has been highlighting an increasingly more important role of gut microbiota in metabolic disorders. It's well known that gut microbiota plays a major role in the development of food absorption and low grade inflammation, two key processes in obesity and diabetes. This review summarizes key discoveries during the past decade that established the role of gut microbiota in the development of obesity and diabetes. It will look at the role of key metabolites mainly the short chain fatty acids (SCFA) that are produced by gut microbiota and how they impact key metabolic pathways such as insulin signalling, incretin production as well as inflammation. It will further look at the possible ways to harness the beneficial aspects of the gut microbiota to combat these metabolic disorders and reduce their impact. PMID:27317359

  13. Incretin-Based Therapy for Prevention of Diabetic Vascular Complications

    PubMed Central

    Mima, Akira

    2016-01-01

    Diabetic vascular complications are the most common cause of mortality and morbidity worldwide, with numbers of affected individuals steadily increasing. Diabetic vascular complications can be divided into two categories: macrovascular andmicrovascular complications. Macrovascular complications include coronary artery diseaseand cerebrovascular disease, while microvascular complications include retinopathy and chronic kidney disease. These complications result from metabolic abnormalities, including hyperglycemia, elevated levels of free fatty acids, and insulin resistance. Multiple mechanisms have been proposed to mediate the adverse effects of these metabolic disorders on vascular tissues, including stimulation of protein kinase C signaling and activation of the polyol pathway by oxidative stress and inflammation. Additionally, the loss of tissue-specific insulin signaling induced by hyperglycemia and toxic metabolites can induce cellular dysfunction and both macro- and microvascular complications characteristic of diabetes. Despite these insights, few therapeutic methods are available for the management of diabetic complications. Recently, incretin-based therapeutic agents, such as glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitors, have been reported to elicit vasotropic actions, suggesting a potential for effecting an actual reduction in diabetic vascular complications. The present review will summarize the relationship between multiple adverse biological mechanisms in diabetes and putative incretin-based therapeutic interventions intended to prevent diabetic vascular complications. PMID:26881236

  14. Effects of Two Dietary Fibers as Part of Ready-to-Eat Cereal (RTEC) Breakfasts on Perceived Appetite and Gut Hormones in Overweight Women

    PubMed Central

    Lafond, David W.; Greaves, Kathryn A.; Maki, Kevin C.; Leidy, Heather J.; Romsos, Dale R.

    2015-01-01

    The effects of an enzyme-hydrolyzed arabinoxylan from wheat (AXOS) versus an intact arabinoxylan from flax (FLAX) added to a ready-to-eat cereal (RTEC) on the postprandial appetitive, hormonal, and metabolic responses in overweight women (BMI 25.0–29.9 kg/m2) were evaluated. Subsequent meal energy intake was also assessed. Two randomized, double-blind, crossover design studies were completed. For trial 1, the participants consumed the following RTEC breakfast, matched for total weight and varied in energy content: low-fiber (LF, 4 g); high-fiber (HF, 15 g) as either AXOS or FLAX. For trial 2, the participants consumed LF, HF-AXOS, and HF-FLAX RTECs but also consumed another LF breakfast that was isocaloric (LF-iso) to that of the HF breakfasts. Perceived appetite and blood samples (trial 2 only) were assessed before and after breakfast. An ad libitum lunch was offered 4 h post-breakfast. No differences in postprandial appetite responses were observed among any breakfasts in either trial. The HF-AXOS and HF-FLAX led to increased postprandial GLP-1 and peptide YY (PYY) concentrations vs. LF-iso. No differences were observed in lunch meal energy intake among breakfast meals in either trial. Collectively, these data suggest that 15 g of low molecular weight fiber added to RTECs did not affect perceived appetite or subsequent energy intake despite differences in satiety hormone signaling in overweight females. PMID:25689743

  15. Effects of two dietary fibers as part of ready-to-eat cereal (RTEC) breakfasts on perceived appetite and gut hormones in overweight women.

    PubMed

    Lafond, David W; Greaves, Kathryn A; Maki, Kevin C; Leidy, Heather J; Romsos, Dale R

    2015-01-01

    The effects of an enzyme-hydrolyzed arabinoxylan from wheat (AXOS) versus an intact arabinoxylan from flax (FLAX) added to a ready-to-eat cereal (RTEC) on the postprandial appetitive, hormonal, and metabolic responses in overweight women (BMI 25.0-29.9 kg/m2) were evaluated. Subsequent meal energy intake was also assessed. Two randomized, double-blind, crossover design studies were completed. For trial 1, the participants consumed the following RTEC breakfast, matched for total weight and varied in energy content: low-fiber (LF, 4 g); high-fiber (HF, 15 g) as either AXOS or FLAX. For trial 2, the participants consumed LF, HF-AXOS, and HF-FLAX RTECs but also consumed another LF breakfast that was isocaloric (LF-iso) to that of the HF breakfasts. Perceived appetite and blood samples (trial 2 only) were assessed before and after breakfast. An ad libitum lunch was offered 4 h post-breakfast. No differences in postprandial appetite responses were observed among any breakfasts in either trial. The HF-AXOS and HF-FLAX led to increased postprandial GLP-1 and peptide YY (PYY) concentrations vs. LF-iso. No differences were observed in lunch meal energy intake among breakfast meals in either trial. Collectively, these data suggest that 15 g of low molecular weight fiber added to RTECs did not affect perceived appetite or subsequent energy intake despite differences in satiety hormone signaling in overweight females. PMID:25689743

  16. Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

    PubMed Central

    Candeias, Emanuel Monteiro; Sebastião, Inês Carolina; Cardoso, Susana Maria; Correia, Sónia Catarina; Carvalho, Cristina Isabel; Plácido, Ana Isabel; Santos, Maria Sancha; Oliveira, Catarina Resende; Moreira, Paula Isabel; Duarte, Ana Isabel

    2015-01-01

    Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for type 2 diabetes (T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors (GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions (e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation (thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2D, stroke and Alzheimer disease (AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss

  17. Effects of solid-phase extraction of plasma in measuring gut metabolic hormones in fasted and fed blood of lean and diet-induced obese rats.

    PubMed

    Reidelberger, Roger; Haver, Alvin; Anders, Krista; Apenteng, Bettye; Lanio, Craig

    2016-05-01

    Glucagon-like peptide-1 (GLP-1), peptide YY (3-36) [PYY(3-36)], amylin, ghrelin, insulin, and leptin are thought to act as hormonal signals from periphery to brain to control food intake. Here, we determined the effects of solid-phase extraction of plasma in measuring these hormones in blood of lean and diet-induced obese rats. Individual enzyme-linked immunoassays and a multiplex assay were used to measure active GLP-1, total PYY, active amylin, active ghrelin, insulin, leptin, and total GIP in response to (1) addition of known amounts of the peptides to lean and obese plasma, (2) a large meal in lean and obese rats, and (3) intravenous infusions of anorexigenic doses of GLP-1, PYY(3-36), amylin, and leptin in lean rats. Extraction of lean and obese plasma prior to assays produced consistent recoveries across assays for GLP-1, PYY, amylin, ghrelin, and insulin, reflecting losses inherent to the extraction procedure. Plasma extraction prior to assays generally revealed larger meal-induced changes in plasma GLP-1, PYY, amylin, ghrelin, and insulin in lean and obese rats. Plasma extraction and the multiplex assay were used to compare plasma levels of GLP-1, PYY, and amylin after a large meal with plasma levels produced by IV infusions of anorexigenic doses of GLP-1, PYY(3-36), and amylin. Infusions produced dose-dependent increases in plasma peptide levels, which were well above their postprandial levels. These results do not support the hypothesis that postprandial plasma levels of GLP-1, PYY(3-36), and amylin are sufficient to decrease food intake by an endocrine mechanism. PMID:27207785

  18. Neuropeptides and the Microbiota-Gut-Brain Axis

    PubMed Central

    Holzer, Peter; Farzi, Aitak

    2015-01-01

    Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gut-brain axis address 4 information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and 4 information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G protein-coupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are

  19. Incretin based drugs and risk of acute pancreatitis in patients with type 2 diabetes: cohort study

    PubMed Central

    Faillie, Jean-Luc; Azoulay, Laurent; Patenaude, Valerie; Hillaire-Buys, Dominique

    2014-01-01

    Objectives To determine whether the use of incretin based drugs, compared with sulfonylureas, is associated with an increased risk of acute pancreatitis. Design Population based cohort study. Setting 680 general practices in the United Kingdom contributing to the Clinical Practice Research Datalink. Participants From 1 January 2007 to 31 March 2012, 20 748 new users of incretin based drugs were compared with 51 712 users of sulfonylureas and followed up until 31 March 2013. Main outcome measures Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for acute pancreatitis in users of incretin based drugs compared with users of sulfonylureas. Models were adjusted for tenths of high dimensional propensity score (hdPS). Results The crude incidence rate for acute pancreatitis was 1.45 per 1000 patients per year (95% confidence interval 0.99 to 2.11) for incretin based drug users and 1.47 (1.23 to 1.76) for sulfonylurea users. The rate of acute pancreatitis associated with the use of incretin based drugs was not increased (hdPS adjusted hazard ratio: 1.00, 95% confidence interval 0.59 to 1.70) relative to sulfonylurea use. Conclusions Compared with use of sulfonylureas, the use of incretin based drugs is not associated with an increased risk of acute pancreatitis. While this study is reassuring, it does not preclude a modest increased risk, and thus additional studies are needed to confirm these findings. PMID:24764569

  20. Mosquito-specific microRNA-1890 targets the juvenile hormone-regulated serine protease JHA15 in the female mosquito gut.

    PubMed

    Lucas, Keira J; Zhao, Bo; Roy, Sourav; Gervaise, Amanda L; Raikhel, Alexander S

    2015-01-01

    Females of the hematophagous mosquito species require a vertebrate blood meal to supply amino acids and other nutrients necessary for egg development, serving as the driving force for the spread of many vector-borne diseases in humans. Blood digestion utilizes both early and late phase serine proteases (SPs) that are differentially regulated at the transcriptional and post-transcriptional level. To uncover the regulatory complexity of SPs in the female mosquito midgut, we investigated involvement of miRNAs in regulating the juvenile hormone (JH)-controlled chymotrypsin-like SP, JHA15. We identified regulatory regions complementary to the mosquito-specific miRNA, miR-1890, within the 3' UTR of JHA15 mRNA. The level of the JHA15 transcript is highest post eclosion and drastically declines post blood meal (PBM), exhibiting an opposite trend to miR-1890 that peaks at 24 h PBM. Depletion of miR-1890 results in defects in blood digestion, ovary development and egg deposition. JHA15 mRNA and protein levels are elevated in female mosquitoes with miR-1890 inhibition. JHA15 RNA interference in the miR-1890 depletion background alleviates miR-1890 depletion phenotypes. The miR-1890 gene is activated by the 20-hydroxyecdysone pathway that involves the ecdysone receptor and the early genes, E74B and Broad Z2. Our study suggests that miR-1890 controls JHA15 mRNA stability in a stage- and tissue- specific manner. PMID:26488481

  1. Contributions of upper gut hormones and motility to the energy intake-suppressant effects of intraduodenal nutrients in healthy, lean men - a pooled-data analysis.

    PubMed

    Schober, Gudrun; Lange, Kylie; Steinert, Robert E; Hutchison, Amy T; Luscombe-Marsh, Natalie D; Landrock, Maria F; Horowitz, Michael; Seimon, Radhika V; Feinle-Bisset, Christine

    2016-09-01

    We have previously identified pyloric pressures and plasma cholecystokinin (CCK) concentrations as independent determinants of energy intake following administration of intraduodenal lipid and intravenous CCK. We evaluated in healthy men whether these parameters also determine energy intake in response to intraduodenal protein, and whether, across the nutrients, any predominant gastrointestinal (GI) factors exist, or many factors make small contributions. Data from nine published studies, in which antropyloroduodenal pressures, GI hormones, and GI /appetite perceptions were measured during intraduodenal lipid or protein infusions, were pooled. In all studies energy intake was quantified immediately after the infusions. Specific variables for inclusion in a mixed-effects multivariable model for determination of independent predictors of energy intake were chosen following assessment for collinearity, and within-subject correlations between energy intake and these variables were determined using bivariate analyses adjusted for repeated measures. In models based on all studies, or lipid studies, there were significant effects for amplitude of antral pressure waves, premeal glucagon-like peptide-1 (GLP-1) and time-to-peak GLP-1 concentrations, GLP-1 AUC and bloating scores (P < 0.05), and trends for basal pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK concentrations, and hunger and nausea scores (0.05 < P ≤ 0.094), to be independent determinants of subsequent energy intake. In the model including the protein studies, only BPP was identified as an independent determinant of energy intake (P < 0.05). No single parameter was identified across all models, and effects of the variables identified were relatively small. Taken together, while GI mechanisms contribute to the regulation of acute energy intake by lipid and protein, their contribution to the latter is much less. Moreover, the effects are likely to reflect small, cumulative

  2. The incretin effect in obese adolescents with and without type 2 diabetes: impaired or intact?

    PubMed

    Aulinger, Benedikt A; Vahl, Torsten P; Prigeon, Ron L; D'Alessio, David A; Elder, Deborah A

    2016-05-01

    The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction and described in T2D, IGT, and even obesity without IGT. We sought to determine the effects of obesity and diabetes on the incretin effect in young subjects with short exposures to metabolic abnormalities and a few other confounding medical conditions. Subjects with T2D (n = 10; 18.0 ± 0.4 yr) or NGT, either obese (n = 11; 17.7 ± 0.4 yr) or lean (n = 8; 26.5 ± 2.3 yr), had OGTT and iso-iv. The incretin effect was calculated as the difference in insulin secretion during these tests and was decreased ∼50% in both the NGT-Ob and T2D subjects relative to the NGT-Ln group. The T2D group had impaired glucose tolerance and insulin secretion during the OGTT, whereas the lean and obese NGT subjects had comparable glucose excursions and β-cell function. During the iso-iv test, the NGT-Ob subjects had significantly greater insulin secretion than the NGT-Ln and T2D groups. These findings demonstrate that in young subjects with early, well-controlled T2D the incretin effect is reduced, similar to what has been described in diabetic adults. The lower incretin effect calculated for the obese subjects with NGT is driven by a disproportionately greater insulin response to iv glucose and does not affect postprandial glucose regulation. These findings confirm that the incretin effect is an early marker of impaired insulin secretion in persons with abnormal glucose tolerance but suggest that in obese subjects with NGT the incretin effect calculation can be confounded by exaggerated insulin secretion to iv glucose. PMID:26979523

  3. Noopept normalizes parameters of the incretin system in rats with experimental diabetes.

    PubMed

    Ostrovskaya, R U; Zolotov, N N; Ozerova, I V; Ivanova, E A; Kapitsa, I G; Taraban, K V; Michunskaya, A M; Voronina, T A; Gudasheva, T A; Seredenin, S B

    2014-07-01

    Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that antihyperglycemic activity of an original nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under conditions of oral application than after intraperitoneal injection. These data provided a basis for studying the effect of Noopept on major indexes of the incretin system. Streptozotocin was shown to decrease the concentrations of incretin GLP-1 and insulin in the blood. Noopept had a normalizing effect on these parameters. This influence of Noopept was not related to the inhibition of a major enzyme metabolizing incretins (dipeptidyl peptidase IV). A reference drug sitagliptin also increased the contents of incretins and insulin, which was associated with the inhibition of dipeptidyl peptidase IV. It is known that GLP-1 increases NGF expression in the insular system. Our results suggest that the increase in incretin activity contributes to the antiapoptotic effect of Noopept on pancreatic β cells. The mechanism for an increase in blood GLP-1 level after oral application of Noopept requires further investigations. PMID:25065315

  4. [Incretin-based antidiabetic treatment and diseases of the pancreas (pancreatitis, pancreas carcinoma)].

    PubMed

    Jermendy, György

    2016-04-01

    In the last couple of years incretin-based antidiabetic drugs became increasingly popular and widely used for treating patients with type 2 diabetes. Immediately after launching, case reports and small case series were published on the potential side effects of the new drugs, with special attention to pancreatic disorders such as acute pancreatitis or pancreatic cancer. As clinical observations accumulated, these side-effects were noted with nearly all drugs of this class. Although these side-effects proved to be rare, an intensive debate evolved in the literature. Opinion of diabetes specialists and representatives of pharmaceutical industry as well as position statements of different international scientific boards and health authorities were published. In addition, results of randomized clinical trials with incretin-based therapy and meta-analyses became available. Importantly, in everyday clinical practice, the label of the given drug should be followed. With regards to incretins, physicians should be cautious if pancreatitis in the patients' past medical history is documented. Early differential diagnosis of any abdominal pain during treatment of incretin-based therapy should be made and the drug should be discontinued if pancreatitis is verified. Continuous post-marketing surveillance and side-effect analysis are still justified with incretin-based antidiabetic treatment in patients with type 2 diabetes. PMID:27017851

  5. Incretin attenuates diabetes-induced damage in rat cardiac tissue.

    PubMed

    AbdElmonem Elbassuoni, Eman

    2014-09-01

    Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

  6. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  7. [Cardiovascular safety of incretin-based antidiabetic treatment - results of completed clinical trials].

    PubMed

    Jermendy, György

    2016-04-17

    Several randomized, controlled clinical trials were initiated some years ago in order to evaluate the cardiovascular safety of the new antidiabetic drugs in patients with type 2 diabetes due to requirements from regulatory bodies. Four trials with incretin-based drugs (saxagliptin, alogliptin, sitagliptin and lixisenatide) have been completed so far. Based on the primary outcome endpoints of these trials no cardiovascular risks were found with incretins in patients with type 2 diabetes. As for saxagliptin, the hospitalization for heart failure was investigated as a secondary endpoint, and an increased risk was observed in the respective trial; however, this observation was widely debated later in the literature. Together with ongoing trials of other novel antihyperglycemic agents, these data will provide more robust evidence about the cardiovascular safety of incretin-based antidiabetic treatment in patients with type 2 diabetes. PMID:27063427

  8. [Potential of pharmacological modulation of level and activity incretins on diabetes mellitus type 2].

    PubMed

    Spasov, A A; Chepljaeva, N I

    2015-01-01

    This review summarizes data on the main approaches used for the search of biologically active compounds modulating the level and physiological activity of incretins. Currently two groups of drugs are used in clinical practice: they either replenish the deficit of incretins (glucagon-like peptide-1 receptor agonists) or inhibit the degradation processes (dipeptidyl peptidase 4 inhibitors). In addition, new groups of substances are actively searched. These include non-peptide agonists of glucagon-like peptide-1 receptors, agonists/antagonists of glucose-dependent insulinotropic peptide, the hybrid polypeptides based on glucagon-like peptide-1 and glucagon. PMID:26350740

  9. The bioactive effects of casein proteins on enteroendocrine cell health, proliferation and incretin hormone secretion.

    PubMed

    Gillespie, Anna L; Green, Brian D

    2016-11-15

    Previous studies suggest that casein exerts various anti-diabetic effects. However, it is not known which casein proteins are bioactive, nor their effects on enteroendocrine cells. This study evaluated the effects of intact whole casein, intact individual proteins (alpha, beta and kappa casein) and hydrolysates on an enteroendocrine cell line. High content analysis accurately monitored changes in cell health and intracellular glucagon-like peptide-1 (GLP-1) content. Cheese ripening duration and GLP-1 secretory responses were also considered. Beta casein significantly stimulated enteroendocrine cell proliferation and all caseins were potent GLP-1 secretagogues (except kappa casein). Interestingly the GLP-1 secretory activity was almost always lost or significantly reduced upon hydrolysis with proteolytic enzymes. Only pepsin-derived beta casein hydrolysates had significantly increased potency compared with the intact protein, but this was diminished with prolonged hydrolysis. In conclusion casein proteins are not detrimental to enteroendocrine cells, and alpha and beta casein are particularly beneficial stimulating proliferation and GLP-1 secretion. PMID:27283618

  10. Anorexia of Aging and Gut Hormones

    PubMed Central

    Atalayer, Deniz; Astbury, Nerys M.

    2013-01-01

    We are expected to live longer than if we had been born 100 years ago however, the additional years are not necessarily spent in good health or free from disability. Body composition changes dramatically over the course of life. There is a gradual increase in body weight throughout adult life until the age of about 60–65 years. In contrast, body weight appears to decrease with age after the age of 65–75 years, even in those demonstrating a previous healthy body weight. This age related decrease in body weight, often called unintentional weight loss or involuntary weight loss can be a significant problem for the elderly. This has been shown to be related to decline in appetite and food intake is common amongst the elderly and is often referred to the anorexia of aging. Underlying mechanisms regulate energy homeostasis and appetite may change as people age. In this review, peripheral factors regulating appetite have been summarized in regards to their age-dependent changes and role in the etiology of anorexia of aging. Understanding the alterations in the mechanisms regulating appetite and food intake in conjunction with aging may help inform strategies that promote healthy aging and promote health and wellbeing in the elderly years, with the end goal to add life to the years and not just years to our lives. PMID:24124632

  11. Anorexia of aging and gut hormones.

    PubMed

    Atalayer, Deniz; Astbury, Nerys M

    2013-01-01

    We are expected to live longer than if we had been born 100 years ago however, the additional years are not necessarily spent in good health or free from disability. Body composition changes dramatically over the course of life. There is a gradual increase in body weight throughout adult life until the age of about 60-65 years. In contrast, body weight appears to decrease with age after the age of 65-75 years, even in those demonstrating a previous healthy body weight. This age related decrease in body weight, often called unintentional weight loss or involuntary weight loss can be a significant problem for the elderly. This has been shown to be related to decline in appetite and food intake is common amongst the elderly and is often referred to the anorexia of aging. Underlying mechanisms regulate energy homeostasis and appetite may change as people age. In this review, peripheral factors regulating appetite have been summarized in regards to their age-dependent changes and role in the etiology of anorexia of aging. Understanding the alterations in the mechanisms regulating appetite and food intake in conjunction with aging may help inform strategies that promote healthy aging and promote health and wellbeing in the elderly years, with the end goal to add life to the years and not just years to our lives. PMID:24124632

  12. The Gut Microbiome and the Brain

    PubMed Central

    Galland, Leo

    2014-01-01

    Abstract The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics. PMID:25402818

  13. Schizophrenia and the gut-brain axis.

    PubMed

    Nemani, Katlyn; Hosseini Ghomi, Reza; McCormick, Beth; Fan, Xiaoduo

    2015-01-01

    Several risk factors for the development of schizophrenia can be linked through a common pathway in the intestinal tract. It is now increasingly recognized that bidirectional communication exists between the brain and the gut that uses neural, hormonal, and immunological routes. An increased incidence of gastrointestinal (GI) barrier dysfunction, food antigen sensitivity, inflammation, and the metabolic syndrome is seen in schizophrenia. These findings may be influenced by the composition of the gut microbiota. A significant subgroup of patients may benefit from the initiation of a gluten and casein-free diet. Antimicrobials and probiotics have therapeutic potential for reducing the metabolic dysfunction and immune dysregulation seen in patients with schizophrenia. PMID:25240858

  14. Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence.

    PubMed

    Kawanami, Daiji; Matoba, Keiichiro; Sango, Kazunori; Utsunomiya, Kazunori

    2016-01-01

    An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications. PMID:27483245

  15. Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

    PubMed Central

    Kawanami, Daiji; Matoba, Keiichiro; Sango, Kazunori; Utsunomiya, Kazunori

    2016-01-01

    An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications. PMID:27483245

  16. SUSY GUT Model Building

    SciTech Connect

    Raby, Stuart

    2008-11-23

    In this talk I discuss the evolution of SUSY GUT model building as I see it. Starting with 4 dimensional model building, I then consider orbifold GUTs in 5 dimensions and finally orbifold GUTs embedded into the E{sub 8}xE{sub 8} heterotic string.

  17. Incretin-based therapies and acute pancreatitis risk: a systematic review and meta-analysis of observational studies.

    PubMed

    Giorda, Carlo B; Sacerdote, Carlotta; Nada, Elisa; Marafetti, Lisa; Baldi, Ileana; Gnavi, Roberto

    2015-03-01

    Concerns raised by several animal studies, case reports, and pharmacovigilance warnings over incretin-based therapy potentially exposing type two diabetes patients to an elevated risk of pancreatitis have cast a shadow on the overall safety of this class of drugs. This systematic review evaluates the data from observational studies that compared treatment with or without incretins and the risk of pancreatitis. We searched PubMed for publications with the key terms incretins or GLP-1 receptor agonists or DPP-4 inhibitors or sitagliptin or vildagliptin or saxagliptin or linagliptin or alogliptin or exenatide or liraglutide AND pancreatitis in the title or abstract. Studies were evaluated against the following criteria: design (either cohort or case-control); outcome definition (incidence of pancreatitis); exposure definition (new or current or past incretins users); and comparison between patients receiving incretins or not for type 2 diabetes. Two authors independently selected the studies and extracted the data. Six studies meeting the inclusion criteria were reviewed. No difference was found in the overall risk of pancreatitis between incretin users and non-users (odds ratio 1.08; 95 % CI [0.84-1.40]). A risk increase lower than 35 % cannot be excluded according to the power calculation. This systematic review and meta-analysis suggests that type 2 diabetes patients receiving incretin-based therapy are not exposed to an elevated risk of pancreatitis. Limitations of this analysis are the low prevalence of incretin users and the lack of a clear distinction by the studies between therapy with DPP-4 inhibitors or with GLP-1 receptor agonists. PMID:25146552

  18. Role of Epac2A/Rap1 signaling in interplay between incretin and sulfonylurea in insulin secretion.

    PubMed

    Takahashi, Harumi; Shibasaki, Tadao; Park, Jae-Hyung; Hidaka, Shihomi; Takahashi, Toshimasa; Ono, Aika; Song, Dae-Kyu; Seino, Susumu

    2015-04-01

    Incretin-related drugs and sulfonylureas are currently used worldwide for the treatment of type 2 diabetes. We recently found that Epac2A, a cAMP binding protein having guanine nucleotide exchange activity toward Rap, is a target of both incretin and sulfonylurea. This suggests the possibility of interplay between incretin and sulfonylurea through Epac2A/Rap1 signaling in insulin secretion. In this study, we examined the combinatorial effects of incretin and various sulfonylureas on insulin secretion and activation of Epac2A/Rap1 signaling. A strong augmentation of insulin secretion by combination of GLP-1 and glibenclamide or glimepiride, which was found in Epac2A(+/+) mice, was markedly reduced in Epac2A(-/-) mice. In contrast, the combinatorial effect of GLP-1 and gliclazide was rather mild, and the effect was not altered by Epac2A ablation. Activation of Rap1 was enhanced by the combination of an Epac-selective cAMP analog with glibenclamide or glimepiride but not gliclazide. In diet-induced obese mice, ablation of Epac2A reduced the insulin secretory response to coadministration of the GLP-1 receptor agonist liraglutide and glimepiride. These findings clarify the critical role of Epac2A/Rap1 signaling in the augmenting effect of incretin and sulfonylurea on insulin secretion and provide the basis for the effects of combination therapies of incretin-related drugs and sulfonylureas. PMID:25315008

  19. Inflammation Meets Metabolic Disease: Gut Feeling Mediated by GLP-1

    PubMed Central

    Zietek, Tamara; Rath, Eva

    2016-01-01

    Chronic diseases, such as obesity and diabetes, cardiovascular, and inflammatory bowel diseases (IBD) share common features in their pathology. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa, inflammation is associated with metabolic alterations. Next to cytokines and cellular stress pathways, such as the unfolded protein response (UPR), alterations in the enteroendocrine system are intersections of various pathologies. Enteroendocrine cells (EEC) have been studied extensively for their ability to regulate gastrointestinal motility, secretion, and insulin release by release of peptide hormones. In particular, the L-cell-derived incretin hormone glucagon-like peptide 1 (GLP-1) has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes (T2D). Yet, accumulating data indicate a critical role for EEC and in particular for GLP-1 in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC sense the lamina propria and luminal environment, including the microbiota via receptors and transporters. Subsequently, mediating signals by secreting hormones and cytokines, EEC can be considered as integrators of metabolic and inflammatory signaling. This review focuses on L cell and GLP-1 functions in the context of metabolic and inflammatory diseases. The effects of incretin-based therapies on metabolism and immune system are discussed and the interrelation and common features of metabolic and immune-mediated disorders are highlighted. Moreover, it presents data on the impact of inflammation, in particular of IBD on EEC and discusses the potential role of the microbiota as link between nutrients, metabolism, immunity, and disease. PMID:27148273

  20. Gut Melatonin in Vertebrates: Chronobiology and Physiology

    PubMed Central

    Mukherjee, Sourav; Maitra, Saumen Kumar

    2015-01-01

    Melatonin, following discovery in the bovine pineal gland, has been detected in several extra-pineal sources including gastrointestinal tract or gut. Arylalkylamine N-acetyltransferase (AANAT) is the key regulator of its biosynthesis. Melatonin in pineal is rhythmically produced with a nocturnal peak in synchronization with environmental light–dark cycle. A recent study on carp reported first that melatonin levels and intensity of a ~23 kDa AANAT protein in each gut segment also exhibit significant daily variations but, unlike pineal, show a peak at midday in all seasons. Extensive experimental studies ruled out direct role of light–dark conditions in determining temporal pattern of gut melatoninergic system in carp, and opened up possible role of environmental non-photic cue(s) as its synchronizer. Based on mammalian findings, physiological significance of gut-derived melatonin also appears unique because its actions at local levels sharing paracrine and/or autocrine functions have been emphasized. The purpose of this mini review is to summarize the existing data on the chronobiology and physiology of gut melatonin and to emphasize their relation with the same hormone derived in the pineal in vertebrates including fish. PMID:26257705

  1. Autophagy deficiency in β cells blunts incretin-induced suppression of glucagon release from α cells.

    PubMed

    Kim, Min Joo; Choi, Ok Kyong; Chae, Kyung Sil; Lee, Hakmo; Chung, Sung Soo; Ham, Dong-Sik; Kim, Ji-Won; Yoon, Kun-Ho; Park, Kyong Soo; Jung, Hye Seung

    2015-09-01

    Incretin-based therapy such as GLP-1 receptor agonists and DPP-4 inhibitors for type 2 diabetes mellitus is characterized by glucose-dependent insulin secretion and glucose-inhibited glucagon secretion. Recently, autophagy deficiency in islet β cells has been shown to contribute to the pathogenesis of type 2 diabetes mellitus however, with the role of incretin has not been established. To evaluate the role of autophagy in incretin effects, 8-week-old male β cell-specific Atg7 knockout (Atg7(Δβ cell)) mice and wild-type mice were administered vildagliptin for 12 weeks. Vildagliptin treatment improved glucose intolerance and hypoinsulinemia; however, it failed to suppress serum glucagon levels after glucose loading in the Atg7(Δβ cell) mice. Ex vivo glucose-induced glucagon suppression was also blunted in the islets from vildagliptin-treated Atg7(Δβ cell) mice. The α cell mass was not affected by β cell autophagy deficiency or vildagliptin. However, glucagon mRNA expression was significantly increased by vildagliptin in the autophagy-deficient islets, and was significantly reduced by vildagliptin in wild-type islets. Pancreatic glucagon contents were not in agreement with the changes in mRNA expression, suggesting a dysregulation in glucagon translation and secretion. In vitro studies revealed that glucose-stimulated cAMP production was impaired in the autophagy-deficient islets exposed to exendin-4. Taken together, the results suggest that the constitutive autophagy in β cells could regulate incretin-induced glucagon expression and release in α cells, and that cAMP may play a role in this process. PMID:26744903

  2. Autophagy deficiency in β cells blunts incretin-induced suppression of glucagon release from α cells

    PubMed Central

    Kim, Min Joo; Choi, Ok Kyong; Chae, Kyung Sil; Lee, Hakmo; Chung, Sung Soo; Ham, Dong-Sik; Kim, Ji-Won; Yoon, Kun-Ho; Park, Kyong Soo; Jung, Hye Seung

    2015-01-01

    Incretin-based therapy such as GLP-1 receptor agonists and DPP-4 inhibitors for type 2 diabetes mellitus is characterized by glucose-dependent insulin secretion and glucose-inhibited glucagon secretion. Recently, autophagy deficiency in islet β cells has been shown to contribute to the pathogenesis of type 2 diabetes mellitus however, with the role of incretin has not been established. To evaluate the role of autophagy in incretin effects, 8-week-old male β cell-specific Atg7 knockout (Atg7Δβ cell) mice and wild-type mice were administered vildagliptin for 12 weeks. Vildagliptin treatment improved glucose intolerance and hypoinsulinemia; however, it failed to suppress serum glucagon levels after glucose loading in the Atg7Δβ cell mice. Ex vivo glucose-induced glucagon suppression was also blunted in the islets from vildagliptin-treated Atg7Δβ cell mice. The α cell mass was not affected by β cell autophagy deficiency or vildagliptin. However, glucagon mRNA expression was significantly increased by vildagliptin in the autophagy-deficient islets, and was significantly reduced by vildagliptin in wild-type islets. Pancreatic glucagon contents were not in agreement with the changes in mRNA expression, suggesting a dysregulation in glucagon translation and secretion. In vitro studies revealed that glucose-stimulated cAMP production was impaired in the autophagy-deficient islets exposed to exendin-4. Taken together, the results suggest that the constitutive autophagy in β cells could regulate incretin-induced glucagon expression and release in α cells, and that cAMP may play a role in this process. PMID:26744903

  3. Incretin-based drugs for type 2 diabetes: Focus on East Asian perspectives.

    PubMed

    Seino, Yutaka; Kuwata, Hitoshi; Yabe, Daisuke

    2016-04-01

    Type 2 diabetes in East Asians is characterized primarily by β-cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are secreted in response to meal ingestion, and enhance insulin secretion glucose-dependently. Incretin-based drugs, dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists, that ameliorate β-cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta-analyses of clinical trials on DPP-4i and glucagon-like peptide-1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of β-cell dysfunction. In addition, we found increased glycated hemoglobin-lowering effects of DPP-4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP-4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP-4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin-associated hypoglycemia by DPP-4i has gained attention with regard to the enhancement of hypoglycemia-induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin-based drugs could have potential as a first choice therapy in

  4. Incretin-based therapies in prediabetes: Current evidence and future perspectives

    PubMed Central

    Papaetis, Georgios S

    2014-01-01

    The prevalence of type 2 diabetes (T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance (NGT) and the clinical entity of T2D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2D. The huge burden resulting from the complications of T2D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, on β-cell function in patients with T2D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2D. PMID:25512784

  5. The cardiovascular safety of incretin-based therapies: a review of the evidence

    PubMed Central

    2013-01-01

    Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in people with diabetes and therefore managing cardiovascular (CV) risk is a critical component of diabetes care. As incretin-based therapies are effective recent additions to the glucose-lowering treatment armamentarium for type 2 diabetes mellitus (T2D), understanding their CV safety profiles is of great importance. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with beneficial effects on CV risk factors, including weight, blood pressure and lipid profiles. Encouragingly, mechanistic studies in preclinical models and in patients with acute coronary syndrome suggest a potential cardioprotective effect of native GLP-1 or GLP-1 receptor agonists following ischaemia. Moreover, meta-analyses of phase 3 development programme data indicate no increased risk of major adverse cardiovascular events (MACE) with incretin-based therapies. Large randomized controlled trials designed to evaluate long-term CV outcomes with incretin-based therapies in individuals with T2D are now in progress, with the first two reporting as this article went to press. PMID:24011363

  6. Dual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis.

    PubMed

    Ali, Safina; Lamont, Benjamin J; Charron, Maureen J; Drucker, Daniel J

    2011-05-01

    Disordered glucagon secretion contributes to the symptoms of diabetes, and reduced glucagon action is known to improve glucose homeostasis. In mice, genetic deletion of the glucagon receptor (Gcgr) results in increased levels of the insulinotropic hormone glucagon-like peptide 1 (GLP-1), which may contribute to the alterations in glucose homeostasis observed in Gcgr-/- mice. Here, we assessed the contribution of GLP-1 receptor (GLP-1R) signaling to the phenotype of Gcgr-/- mice by generating Gcgr-/-Glp1r-/- mice. Although insulin sensitivity was similar in all genotypes, fasting glucose was increased in Gcgr-/-Glp1r-/- mice. Elimination of the Glp1r normalized gastric emptying and impaired intraperitoneal glucose tolerance in Gcgr-/- mice. Unexpectedly, deletion of Glp1r in Gcgr-/- mice did not alter the improved oral glucose tolerance and increased insulin secretion characteristic of that genotype. Although Gcgr-/-Glp1r-/- islets exhibited increased sensitivity to the incretin glucose-dependent insulinotropic polypeptide (GIP), mice lacking both Glp1r and the GIP receptor (Gipr) maintained preservation of the enteroinsular axis following reduction of Gcgr signaling. Moreover, Gcgr-/-Glp1r-/- islets expressed increased levels of the cholecystokinin A receptor (Cckar) and G protein-coupled receptor 119 (Gpr119) mRNA transcripts, and Gcgr-/-Glp1r-/- mice exhibited increased sensitivity to exogenous CCK and the GPR119 agonist AR231453. Our data reveal extensive functional plasticity in the enteroinsular axis via induction of compensatory mechanisms that control nutrient-dependent regulation of insulin secretion. PMID:21540554

  7. Gut microbiota and obesity.

    PubMed

    Gérard, Philippe

    2016-01-01

    The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity. PMID:26459447

  8. Gastrointestinal dopamine as an anti-incretin and its possible role in bypass surgery as therapy for type 2 diabetes with associated obesity.

    PubMed

    Chaudhry, Suleman; Bernardes, Marilia; Harris, Paul E; Maffei, Antonella

    2016-03-01

    The objective of this review was to summarize and integrate specific clinical observations from the field of gastric bypass surgery and recent findings in beta cell biology. When considered together, these data sets suggest a previously unrecognized physiological mechanism which may explain how Roux-en-Y gastric bypass (RYGB) surgery mediates the early rapid reversal of hyperglycemia, observed before weight loss, in certain type 2 diabetes mellitus (T2DM) patients. The novel mechanism is based on a recently recognized inhibitory circuit of glucose stimulated insulin secretion driven by DA stored in β-cell vesicles and the gut. We propose that DA and glucagon-like peptide 1 (GLP-1) represent two opposing arms of a glucose stimulated insulin secretion (GSIS) regulatory system and hypothesize that dopamine represents the "anti-incretin" hypothesized to explain the beneficial effects of bariatric surgery on T2DM. These new hypotheses and the research driven by them may directly impact our understanding of: 1) the mechanisms underlying improved glucose homeostasis seen before weight loss following bariatric surgery; and 2) the regulation of glucose stimulated insulin secretion within islets. On a practical level, these studies may result in the development of novels drugs to modulate insulin secretion and/or methods to quantitatively asses in real time beta cell function and mass. PMID:26505694

  9. The incretins: from the concept to their use in the treatment of type 2 diabetes. Part A: incretins: concept and physiological functions.

    PubMed

    Girard, J

    2008-12-01

    This paper briefly reviews the concept of incretins and describes the biological effects of the two incretins identified so far: the glucose-dependent insulinotropic polypeptide (GIP); and the glucagon-like peptide-1 (GLP-1). GIP is released by the Kcells of the duodenum, while GLP-1 is released by the Lcells of the distal ileum, in response to nutrient absorption. GIP and GLP-1 stimulate insulin biosynthesis and insulin secretion in a glucose-dependent manner. In addition, they increase beta-cell mass. GIP has a specific effect on adipose tissue to facilitate the efficient disposal of absorbed fat and, thus, may be involved in the development of obesity. GLP-1 has specific effects on pancreatic alpha cells, the hypothalamus, and gastrointestinal and cardiovascular systems. By inhibiting glucagon secretion and delaying gastric-emptying, GLP-1 plays an important role in glucose homoeostasis and, by inhibiting food intake, prevents the increase in body weight. As the metabolic effects of GIP are blunted in type 2 diabetes, this peptide cannot be used as an efficient therapy for diabetes. In contrast, GLP-1 effects are preserved at high concentrations in type 2 diabetes, making this peptide of great interest for the treatment of diabetes, a topic that will be discussed in the second part of this review. PMID:19036624

  10. Dipeptidylpeptidase-IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats

    PubMed Central

    Tarantola, E.; Bertone, V.; Milanesi, G.; Capelli, E.; Ferrigno, A.; Neri, D.; Vairetti, M.; Barni, S.; Freitas, I.

    2012-01-01

    Given the scarcity of donors, moderately fatty livers (FLs) are currently being considered as possible grafts for orthotopic liver transplantation (OLT), notwithstanding their poor tolerance to conventional cold preservation. The behaviour of parenchymal and sinusoidal liver cells during transplantation is being studied worldwide. Much less attention has been paid to the biliary tree, although this is considered the Achille's heel even of normal liver transplantation. To evaluate the response of the biliary compartment of FLs to the various phases of OLT reliable markers are necessary. Previously we demonstrated that Alkaline Phosphatase was scarcely active in bile canaliculi of FLs and thus ruled it out as a marker. As an alternative, dipeptidylpeptidase-IV (DPP-IV), was investigated. This ecto-peptidase plays an important role in glucose metabolism, rapidly inactivating insulin secreting hormones (incretins) that are important regulators of glucose metabolism. DPP-IV inhibitors are indeed used to treat Type II diabetes. Neuropeptides regulating bile transport and composition are further important substrates of DPP-IV in the enterohepatic axis. DPP-IV activity was investigated with an azo-coupling method in the liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. Protein expression was studied by immunofluorescence with the monoclonal antibody (clone 5E8). In Wistar rat liver, DPP-IV activity and expression were high in the whole biliary tree, and moderate in sinusoid endothelial cells, in agreement with the literature. Main substrates of DPP-IV in hepatocytes and cholangiocytes could be incretins GLP-1 and GIP, and neuropeptides such as vasoactive intestinal peptide (VIP) and substance P, suggesting that these substances are inactivated or modified through the biliary route. In lean Zucker rat liver the enzyme reaction and protein expression patterns were similar to those of Wistar rat. In obese rat liver the patterns

  11. Gut microbiota and host metabolism in liver cirrhosis

    PubMed Central

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-01-01

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  12. Gut microbiota and host metabolism in liver cirrhosis.

    PubMed

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-11-01

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  13. Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study

    PubMed Central

    Filion, Kristian B; Platt, Robert W; Dahl, Matthew; Dormuth, Colin R; Clemens, Kristin K; Durand, Madeleine; Juurlink, David N; Targownik, Laura E; Turin, Tanvir C; Paterson, J Michael; Ernst, Pierre

    2016-01-01

    Objective To determine whether the use of incretin based drugs compared with sulfonylureas is associated with an increased risk of incident pancreatic cancer in people with type 2 diabetes. Design Population based cohort. Setting Large, international, multicentre study combining the health records from six participating sites in Canada, the United States, and the United Kingdom. Participants A cohort of 972 384 patients initiating antidiabetic drugs between 1 January 2007 and 30 June 2013, with follow-up until 30 June 2014. Main outcome measures Within each cohort we conducted nested case-control analyses, where incident cases of pancreatic cancer were matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and duration of follow-up. Hazard ratios and 95% confidence intervals for incident pancreatic cancer were estimated, comparing use of incretin based drugs with use of sulfonylureas, with drug use lagged by one year for latency purposes. Secondary analyses assessed whether the risk varied by class (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) or by duration of use (cumulative duration of use and time since treatment initiation). Site specific hazard ratios were pooled using random effects models. Results During 2 024 441 person years of follow-up (median follow-up ranging from 1.3 to 2.8 years; maximum 8 years), 1221 patients were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with sulfonylureas, incretin based drugs were not associated with an increased risk of pancreatic cancer (pooled adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.23). Similarly, the risk did not vary by class and evidence of a duration-response relation was lacking. Conclusions In this large, population based study the use of incretin based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas

  14. Gut microbiota, obesity and diabetes.

    PubMed

    Patterson, Elaine; Ryan, Paul M; Cryan, John F; Dinan, Timothy G; Ross, R Paul; Fitzgerald, Gerald F; Stanton, Catherine

    2016-05-01

    The central role of the intestinal microbiota in the progression and, equally, prevention of metabolic dysfunction is becoming abundantly apparent. The symbiotic relationship between intestinal microbiota and host ensures appropriate development of the metabolic system in humans. However, disturbances in composition and, in turn, functionality of the intestinal microbiota can disrupt gut barrier function, a trip switch for metabolic endotoxemia. This low-grade chronic inflammation, brought about by the influx of inflammatory bacterial fragments into circulation through a malfunctioning gut barrier, has considerable knock-on effects for host adiposity and insulin resistance. Conversely, recent evidence suggests that there are certain bacterial species that may interact with host metabolism through metabolite-mediated stimulation of enteric hormones and other systems outside of the gastrointestinal tract, such as the endocannabinoid system. When the abundance of these keystone species begins to decline, we see a collapse of the symbiosis, reflected in a deterioration of host metabolic health. This review will investigate the intricate axis between the microbiota and host metabolism, while also addressing the promising and novel field of probiotics as metabolic therapies. PMID:26912499

  15. Gut failure in the ICU.

    PubMed

    Puleo, Francesco; Arvanitakis, Marianna; Van Gossum, André; Preiser, Jean-Charles

    2011-10-01

    The role of dysfunction of the gastrointestinal tract in the pathogenesis of multiple organ failure (MOF) complicating the course of critically ill patients has been suspected for more than 40 years. However, several hypotheses have been proposed and sometimes refuted to establish a link. This review summarizes the current knowledge on gastrointestinal physiology and recapitulates existing evidence on the link between gastrointestinal dysfunction and MOF. The gastrointestinal tract has various functions apart from digestion. It produces hormones with local and systemic effects, plays a major role in immunological function, and serves as a barrier against antigens within its lumen. Gastrointestinal dysfunction or gut failure is frequently encountered in critical care patients and is associated with bacterial translocation, which can lead to the development of sepsis, initiation of a cytokine-mediated systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and death. The aim of this manuscript is to define gut failure, to review physiopathological mechanisms and clinical implications, and, finally, to suggest preventive measures. PMID:21989698

  16. Small intestinal glucose exposure determines the magnitude of the incretin effect in health and type 2 diabetes.

    PubMed

    Marathe, Chinmay S; Rayner, Christopher K; Bound, Michelle; Checklin, Helen; Standfield, Scott; Wishart, Judith; Lange, Kylie; Jones, Karen L; Horowitz, Michael

    2014-08-01

    The potential influence of gastric emptying on the "incretin effect," mediated by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), is unknown. The objectives of this study were to determine the effects of intraduodenal (ID) glucose infusions at 2 (ID2) and 4 (ID4) kcal/min (equating to two rates of gastric emptying within the physiological range) on the size of the incretin effect, gastrointestinal glucose disposal (GIGD), plasma GIP, GLP-1, and glucagon secretion in health and type 2 diabetes. We studied 10 male BMI-matched controls and 11 male type 2 patients managed by diet or metformin only. In both groups, GIP, GLP-1, and the magnitude of incretin effect were greater with ID4 than ID2, as was GIGD; plasma glucagon was suppressed by ID2, but not ID4. There was no difference in the incretin effect between the two groups. Based on these data, we conclude that the rate of small intestinal glucose exposure (i.e., glucose load) is a major determinant of the comparative secretion of GIP and GLP-1, as well as the magnitude of the incretin effect and GIGD in health and type 2 diabetes. PMID:24696447

  17. Cardiovascular Effect of Incretin-Based Therapy in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis

    PubMed Central

    Kim, Je-Yon; Yang, Seungwon; Lee, Jangik I.; Chang, Min Jung

    2016-01-01

    Background To assess the cardiovascular (CV) risk associated with the use of incretin-based therapy in adult patients with type 2 diabetes mellitus (T2DM) primary prevention group with low CV risks. Methods The clinical studies on incretin-based therapy published in medical journals until August 2014 were comprehensively searched using MEDLINE, EMBASE and CENTRAL with no language restriction. The studies were systemically reviewed and evaluated for CV risks using a meta-analysis approach and where they meet the following criteria: clinical trial, incidence of predefined CV disease, T2DM with no comorbidities, age > 18 years old, duration of at least 12 weeks, incretin-based therapy compared with other antihyperglycaemic agents or placebo. Statistical analyses were performed using a Mantel-Haenszel (M-H) test. The odds ratios (OR) and their 95% confidence interval (CI) were estimated and displayed for comparison. Results A total of 75 studies comprising 45,648 patients with T2DM were selected. The pooled estimate demonstrated no significance in decreased CV risk with incretin-based therapy versus control (M-H OR, 0.90; 95% CI, 0.81–1.00). Conclusions This meta-analysis suggests that incretin-based therapy show no significant protective effect on CV events in T2DM primary prevention group with low CV risks. Prospective randomized controlled trials are required to confirm the results of this analysis. PMID:27078018

  18. Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP.

    PubMed

    Lu, Wendell J; Yang, Qing; Yang, Li; Lee, Dana; D'Alessio, David; Tso, Patrick

    2012-06-01

    Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins produced in the intestine that play a central role in glucose metabolism and insulin secretion. Circulating concentrations of GLP-1 and GIP are low and can be difficult to assay in rodents. These studies utilized the novel intestinal lymph fistula model we have established to investigate the mechanism of lipid-stimulated incretin secretion. Peak concentrations of GLP-1 and GIP following an enteral lipid stimulus (Liposyn) were significantly higher in intestinal lymph than portal venous plasma. To determine whether lipid-stimulated incretin secretion was related to chylomicron formation Pluronic L-81 (L-81), a surfactant inhibiting chylomicron synthesis, was given concurrently with Liposyn. The presence of L-81 almost completely abolished the increase in lymph triglyceride seen with Liposyn alone (P < 0.001). Inhibition of chylomicron formation with L-81 reduced GLP-1 secretion into lymph compared to Liposyn stimulation alone (P = 0.034). The effect of L-81 relative to Liposyn alone had an even greater effect on GIP secretion, which was completely abolished (P = 0.004). These findings of a dramatic effect of L-81 on lymph levels of GLP-1 and GIP support a strong link between intestinal lipid absorption and incretin secretion. The relative difference in the effect of L-81 on the two incretins provides further support that nutrient-stimulation of GIP and GLP-1 is via distinct mechanisms. PMID:22297815

  19. Obesity Surgery and Gut-Brain Communication

    PubMed Central

    Berthoud, Hans-Rudolf; Shin, Andrew C.; Zheng, Huiyuan

    2011-01-01

    The prevalence of obesity, and the cluster of serious metabolic diseases it is associated with, continues to rise globally, and hopes for effective treatment with drugs have been considerably set back. Thus, success with bariatric surgeries to induce sustained body weight loss and effectively cure most of the associated co-morbidities appears almost “miraculous” and systematic investigation of the mechanisms at work has gained momentum. Here, we will discuss the basic organization of gut-brain communication and review clinical and pre-clinical investigations on the potential mechanisms by which gastric bypass surgery leads to its beneficial effects on energy balance and glucose homeostasis. Although a lot has been learned regarding changes in energy intake and expenditure, secretion of gut hormones, and improvement in glucose homeostasis, there has not yet been the “breakthrough observation” of identifying a key signaling component common to the beneficial effects of the surgery. However, given the complexity and redundancy of gut-brain signaling and gut signaling to other relevant organs, it is perhaps more realistic to expect a number of key signaling changes that act in concert to bring about the “miracle”. PMID:21315095

  20. Can a Bug in the Gut Act Like a Drug in the Brain?

    PubMed

    Howland, Robert H

    2015-10-01

    Microorganisms inhabiting the gut exist in a symbiotic relationship with our bodies, performing many essential metabolic tasks for human physiology. The gut-brain axis is a bidirectional communication system integrating neural, hormonal, and immunological signaling between the gut and brain. There is strong experimental evidence from animal studies that the intestinal microbiome has an important role in the control of brain development, function, and behavior. A small number of clinical studies, mainly in healthy individuals, using probiotic formulations as an experimental probe suggest that gut bugs may indeed act like a drug and affect the brain, but much more work is needed. PMID:26489100

  1. Incretin-based drugs and adverse pancreatic events: almost a decade later and uncertainty remains.

    PubMed

    Azoulay, Laurent

    2015-06-01

    Over the past few years, substantial clinical data have been presented showing that incretin-based therapies are effective glucose-lowering agents. Specifically, glucagon-like peptide 1 receptor agonists demonstrate an efficacy comparable to insulin treatment with minimal hypoglycemia and have favorable effects on body weight. Thus, many of the unmet clinical needs noted from prior therapies are addressed by these agents. However, even after many years of use, many continue to raise concerns about the long-term safety of these agents and, in particular, the concern with pancreatitis. This clearly remains a complicated topic. Thus, in this issue of Diabetes Care, we continue to update our readers on this very important issue by presenting two studies evaluating incretin-based medications and risk of pancreatitis. Both have undergone significant revisions based on peer review that provided significant clarification of the data. We applaud both author groups for being extremely responsive in providing the additional data and revisions requested by the editorial team. As such, because of the critical peer review, we feel both articles achieve the high level we require for Diabetes Care and are pleased to now present them to our readers. In keeping with our aim to comprehensively evaluate this topic, we asked for additional commentaries to be prepared. In the narrative outlined below, Dr. Laurent Azoulay provides a commentary about the remaining uncertainty in this area and also discusses the results from a nationwide population-based case-control study. In the narrative preceding Dr. Azoulay's contribution, Prof. Edwin A.M. Gale provides a commentary on the report that focuses on clinical trials of liraglutide in the treatment of diabetes. From the journal's perspective, both of the articles on pancreatitis and incretin-based therapies reported in this issue have been well vetted, and we feel both of the commentaries are insightful. PMID:25998285

  2. Effects of meal size and composition on incretin, alpha-cell, and beta-cell responses.

    PubMed

    Rijkelijkhuizen, Josina M; McQuarrie, Kelly; Girman, Cynthia J; Stein, Peter P; Mari, Andrea; Holst, Jens J; Nijpels, Giel; Dekker, Jacqueline M

    2010-04-01

    The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate postprandial insulin release from the beta-cells. We investigated the effects of 3 standardized meals with different caloric and nutritional content in terms of postprandial glucose, insulin, glucagon, and incretin responses. In a randomized crossover study, 18 subjects with type 2 diabetes mellitus and 6 healthy volunteers underwent three 4-hour meal tolerance tests (small carbohydrate [CH]-rich meal, large CH-rich meal, and fat-rich meal). Non-model-based and model-based estimates of beta-cell function and incremental areas under the curve of glucose, insulin, C-peptide, glucagon, GLP-1, and GIP were calculated. Mixed models and Friedman tests were used to test for differences in meal responses. The large CH-rich meal and fat-rich meal resulted in a slightly larger insulin response as compared with the small CH-rich meal and led to a slightly shorter period of hyperglycemia, but only in healthy subjects. Model-based insulin secretion estimates did not show pronounced differences between meals. Both in healthy individuals and in those with diabetes, more CH resulted in higher GLP-1 release. In contrast with the other meals, GIP release was still rising 2 hours after the fat-rich meal. The initial glucagon response was stimulated by the large CH-rich meal, whereas the fat-rich meal induced a late glucagon response. Fat preferentially stimulates GIP secretion, whereas CH stimulates GLP-1 secretion. Differences in meal size and composition led to differences in insulin and incretin responses but not to differences in postprandial glucose levels of the well-controlled patients with diabetes. PMID:19846181

  3. Association of Type 2 Diabetes Candidate Polymorphisms in KCNQ1 With Incretin and Insulin Secretion

    PubMed Central

    Müssig, Karsten; Staiger, Harald; Machicao, Fausto; Kirchhoff, Kerstin; Guthoff, Martina; Schäfer, Silke A.; Kantartzis, Konstantinos; Silbernagel, Günther; Stefan, Norbert; Holst, Jens J.; Gallwitz, Baptist; Häring, Hans-Ulrich; Fritsche, Andreas

    2009-01-01

    OBJECTIVE KCNQ1 gene polymorphisms are associated with type 2 diabetes. This linkage appears to be mediated by altered β-cell function. In an attempt to study underlying mechanisms, we examined the effect of four KCNQ1 single nucleotide polymorphisms (SNPs) on insulin secretion upon different stimuli. RESEARCH DESIGN AND METHODS We genotyped 1,578 nondiabetic subjects at increased risk of type 2 diabetes for rs151290, rs2237892, rs2237895, and rs2237897. All participants underwent an oral glucose tolerance test (OGTT); glucagon-like peptide (GLP)-1 and gastric inhibitory peptide secretion was measured in 170 participants. In 519 participants, a hyperinsulinemic-euglycemic clamp was performed, in 314 participants an intravenous glucose tolerance test (IVGTT), and in 102 subjects a hyperglycemic clamp combined with GLP-1 and arginine stimuli. RESULTS rs151290 was nominally associated with 30-min C-peptide levels during OGTT, first-phase insulin secretion, and insulinogenic index after adjustment in the dominant model (all P ≤ 0.01). rs2237892, rs2237895, and rs2237897 were nominally associated with OGTT-derived insulin secretion indexes (all P < 0.05). No SNPs were associated with β-cell function during intravenous glucose or GLP-1 administration. However, rs151290 was associated with glucose-stimulated gastric inhibitory polypeptide and GLP-1 increase after adjustment in the dominant model (P = 0.0042 and P = 0.0198, respectively). No associations were detected between the other SNPs and basal or stimulated incretin levels (all P ≥ 0.05). CONCLUSIONS Common genetic variation in KCNQ1 is associated with insulin secretion upon oral glucose load in a German population at increased risk of type 2 diabetes. The discrepancy between orally and intravenously administered glucose seems to be explained not by altered incretin signaling but most likely by changes in incretin secretion. PMID:19366866

  4. Effect of Low- and High-Glycemic Load on Circulating Incretins in a Randomized Clinical Trial

    PubMed Central

    Runchey, Shauna S.; Valsta, Liisa M.; Schwarz, Yvonne; Wang, Chiachi; Song, Xiaoling; Lampe, Johanna W.; Neuhouser, Marian L.

    2012-01-01

    Objective Low-glycemic load diets lower post-prandial glucose and insulin responses; however, the effect of glycemic load on circulating incretin concentrations is unclear. We aimed assess effects of dietary glycemic load on fasting and post-prandial glucose, insulin and incretin (i.e., glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)) concentrations and to examine for effect modification by adiposity. Materials and Methods We conducted a single-center, randomized controlled crossover feeding trial in which a subset of participants had post-prandial testing. Participants were recruited from the local Seattle area. We enrolled 89 overweight-obese (BMI 28.0–39.9 kg/m2) and lean (BMI 18.5–25.0 kg/m2) healthy adults. Participants consumed two 28-day, weight-maintaining high- and low-glycemic load controlled diets in random order. Primary outcome measures were post-prandial circulating concentrations of glucose, insulin, GIP and GLP-1, following a test breakfast. Results Of the 80 participants completing both diet interventions, 16 had incretin testing and comprise the group for analyses. Following each 28-day high- and low-glycemic load diet, mean fasting concentrations of insulin, glucose, GIP and GLP-1 were not significantly different. Mean integrated post-prandial concentrations of glucose, insulin and GIP were higher (1504±476 mg/dL/min, p<0.01; 2012±644 µU/mL/min, p<0.01 and 15517±4062 pg/ml/min, p<0.01, respectively) and GLP-1 was lower (−81.6±38.5 pmol/L/min, p<0.03) following the high-glycemic load breakfast as compared to the low-glycemic load breakfast. Body fat did not significantly modify the effect of glycemic load on metabolic outcomes. Conclusions High-glycemic load diets in weight-maintained healthy individuals leads to higher post-prandial GIP and lower post-prandial GLP-1 concentrations. Future studies evaluating dietary glycemic load manipulation of incretin effects would be helpful for establishing

  5. Treating obesity: is it all in the gut?

    PubMed

    Davenport, Richard J; Wright, Susanne

    2014-07-01

    Obesity is a leading cause of preventable mortality worldwide, with current strategies for treatment including life-style changes, pharmacological intervention and bariatric surgery. With pharmacological intervention showing at best modest patient benefits, new treatments are required. Modulation of anorectic gut hormones could offer the potential to elicit the required life-changing level of efficacy only currently seen with bariatric surgery, and without the cardiovascular risk associated with a number of the current marketed therapies. This review will discuss the gut hormones glucagon-like peptide-1 (GLP-1), Ghrelin and cholecystokinin (CCK)--for which more advanced non-peptide chemical matter has been discovered acting through these hormone pathways and/or their receptors. PMID:24291217

  6. Low calorie sweeteners: Evidence remains lacking for effects on human gut function.

    PubMed

    Bryant, Charlotte; Mclaughlin, John

    2016-10-01

    The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars. PMID:27133729

  7. Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm.

    PubMed

    Wilding, John P H; Rajeev, Surya Panicker; DeFronzo, Ralph A

    2016-08-01

    Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of type 2 diabetes and became available after the introduction of incretin-based therapies, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their weight loss-promoting effect, low risk of hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with empagliflozin). Apart from these clinically important outcomes, they may also correct core defects present in type 2 diabetes (i.e., improvement in β-cell function and insulin sensitivity). They do, however, have some adverse effects, notably, nausea with GLP-1 RAs and genital tract infections and potential for volume depletion with SGLT2i. Whether incretin-based therapies are associated with an increased risk of pancreatitis is unclear. Most recently, diabetic ketoacidosis has been reported with SGLT2i. Therefore, a key clinical question in relation to guidelines is whether these clinical advantages, in the context of the adverse effect profile, outweigh the additional cost compared with older, more established therapies. This article reviews the therapeutic rationale for the use of these newer drugs for diabetes treatment, considers their place in current guidelines, and discusses how this may change as new data emerge about their long-term efficacy and safety from ongoing outcome trials. PMID:27440828

  8. Management of unmet needs in type 2 diabetes mellitus: the role of incretin agents.

    PubMed

    Goldenberg, Ronald M

    2011-12-01

    The leading cause of morbidity and mortality in type 2 diabetes mellitus is cardiovascular disease. There is a need for type 2 diabetes therapies that act in concert with available agents to provide adequate glycemic control without causing hypoglycemia and weight gain, which are associated with increases in cardiovascular risk. Incretin-based agents-dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists-are the newest class of antihyperglycemic therapies. Liraglutide and exenatide, glucagon-like peptide-1 receptor agonists recently approved in Canada, have been shown to effectively lower blood glucose levels while also having beneficial effects on body weight and systolic blood pressure. The objective of this article is to review and discuss incretin-based agents, with a focus on their effects on blood glucose control, body weight and cardiovascular risk factors in patients with type 2 diabetes. Relevant data were obtained by literature search using the EMBASE, MEDLINE and PubMed databases. PMID:24854977

  9. Nor-1, a novel incretin-responsive regulator of insulin genes and insulin secretion⋆

    PubMed Central

    Ordelheide, Anna-Maria; Gerst, Felicia; Rothfuss, Oliver; Heni, Martin; Haas, Carina; Thielker, Inga; Herzberg-Schäfer, Silke; Böhm, Anja; Machicao, Fausto; Ullrich, Susanne; Stefan, Norbert; Fritsche, Andreas; Häring, Hans-Ulrich; Staiger, Harald

    2013-01-01

    B-cell failure at the onset of type 2 diabetes is caused by a decline in β-cell function in the postprandial state and loss of pancreatic β-cell mass. Recently, we showed an association between increased insulin secretion and a single nucleotide polymorphism (SNP), SNP rs12686676, in the NR4A3 gene locus encoding the nuclear receptor Nor-1. Nor-1 is expressed in β-cells, however, not much is known about its function with regard to insulin gene expression and insulin secretion. Nor-1 is induced in a glucose-/incretin-dependent manner via the PKA pathway and directly induces insulin gene expression. Additionally, it stimulates insulin secretion possibly via regulation of potentially important genes in insulin exocytosis. Moreover, we show that the minor allele of NR4A3 SNP rs12686676 fully rescues incretin resistance provoked by a well-described polymorphism in TCF7L2. Thus, Nor-1 represents a promising new target for pharmacological intervention to fight diabetes. PMID:24044104

  10. Cardiac protection via metabolic modulation: an emerging role for incretin-based therapies?

    PubMed

    McCormick, Liam M; Kydd, Anna C; Dutka, David P

    2012-12-01

    Cardiovascular disease continues to be a major cause of morbidity and mortality in patients with Type 2 Diabetes Mellitus. Whilst a focus on improved glucose control and HbA1c has led to a reduction in the progression and development of microvascular complications, the potential for this strategy to reduce cardiovascular event rates is less clearly defined. Identification of the incretin axis has facilitated the development of several novel therapeutic agents which target glucagon-like peptide-1 (GLP-1) pathways. The effects on glucose homeostasis are now established, but there is also now an increasing body of evidence to support a number of pleiotropic effects on the heart that may have the potential to influence cardiovascular outcomes. In this article, we review myocardial energy metabolism with particular emphasis on the potential benefits associated with a shift towards increased glucose utilisation and present the pre-clinical and clinical evidence regarding incretin effects on the heart. In addition we discuss the potential mechanism of action and benefit of drugs that modulate GLP-1 in patients with type 2 diabetes mellitus and coronary artery disease. PMID:22827290

  11. Hadronic EDMs in SUSY GUTs

    SciTech Connect

    Kakizaki, Mitsuru

    2005-12-02

    We investigate the constraints from the null results of the hadronic electric dipole moment (EDM) searches on supersymmetric grand unified theories (SUSY GUTs). Especially we focus on (i) SUSY SU(5) GUTs with right-handed neutrinos and (ii) orbifold GUTs, where the GUT symmetry and SUSY are both broken by boundary conditions in the compactified extra dimensions. We demonstrate that the hadronic EDM experiments severely constrain SUSY GUT models. The interplay between future EDM and LFV experiments will probe the structures of the GUTs and the SUSY breaking mediation mechanism.

  12. Incretin-based drugs and risk of acute pancreatitis: A nested-case control study within a healthcare database.

    PubMed

    Soranna, Davide; Bosetti, Cristina; Casula, Manuela; Tragni, Elena; Catapano, Alberico L; Vecchia, Carlo L A; Merlino, Luca; Corrao, Giovanni

    2015-05-01

    To assess the association between use of incretin-based drugs for diabetes mellitus and the occurrence of acute pancreatitis. A population-based, nested case-control study was performed within a cohort of 166,591 patients from the Lombardy region (Italy) aged 40 years or older who were newly treated with oral antihyperglycaemic agents between 2004 and 2007. Cases were 666 patients who experienced acute pancreatitis from April 1, 2008 until December 31, 2012. For each case patient, up to 20 controls were randomly selected from the cohort and matched on gender, age at cohort entry, and date of index prescription. Conditional logistic regression was used to model the risk of acute pancreatitis associated with use of incretin-based drugs within 30 days before hospitalization, after adjustment for several risk factors, including the use of other antihyperglycaemic agents. Sensitivity analyses were performed in order to account for possible sources of systematic uncertainty. Use of incretin-based drugs within 30 days was reported by 17 (2.6%) cases of acute pancreatitis versus 193 (1.5%) controls. The corresponding multivariate odds ratio was 1.75 (95% confidence interval, 1.02 to 2.99). Slightly lower and no significant excess risks were observed by shortening (15 days) and increasing (60 and 90 days) the time-window at risk. This study supports a possible increased risk of acute pancreatitis in relation to use of incretin-based drugs reported in a few previous studies. However, given the potential for bias and the inconsistency with other studies, additional investigations are needed to clarify the safety of incretin-based-drugs. PMID:25748827

  13. Extracts from Epilobium sp. herbs, their components and gut microbiota metabolites of Epilobium ellagitannins, urolithins, inhibit hormone-dependent prostate cancer cells-(LNCaP) proliferation and PSA secretion.

    PubMed

    Stolarczyk, Magdalena; Piwowarski, Jakub P; Granica, Sebastian; Stefańska, Joanna; Naruszewicz, Marek; Kiss, Anna K

    2013-12-01

    Extracts from Epilobium sp. herbs have been traditionally used in the treatment of prostate-associated ailments. Our studies demonstrated that the extracts from Epilobium angustifolium, Epilobium parviflorum and Epilobium hirsutum herbs are potent prostate cancer cells (LNCaP) proliferation inhibitors with IC50 values around 35 µg/ml. The tested extracts reduced prostate specific antigen (PSA) secretion (from 325.6 ± 25.3 ng/ml to ~90 ng/ml) and inhibited arginase activity (from 65.2 ± 1.1 mUnits of urea/mg of protein to ~40 mUnits of urea/mg protein). Selected constituents of extracts (oenothein B, quercetin-3-O-glucuronide, myricetin-3-O-rhamnoside) were proven to be active in relation to LNCaP cells. However, oenothein B was the strongest inhibitor of cells proliferation (IC50  = 7.8 ± 0.8 μM), PSA secretion (IC50  = 21.9 ± 3.2 μM) and arginase activity (IC50 = 19.2 ± 2.0 μM). Additionally, ellagitannins from E. hirustum extract were proven to be transformed by human gut microbiota into urolithins. Urolithin C showed the strongest activity in the inhibition of cell proliferation (IC50  = 35.2 ± 3.7 μM), PSA secretion (reduced PSA secretion to the level of 100.7 ± 31.0 ng/ml) and arginase activity (reduced to the level of 27.9 ± 3.3 mUnits of urea/mg of protein). Results of the work offer an explanation of the activity of Epilobium extracts and support the use of Epilobium preparations in the treatment of prostate diseases. PMID:23436427

  14. Healthy human gut phageome.

    PubMed

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health. PMID:27573828

  15. Incretin-based therapy: Is the risk of pancreatitis driven by cardiovascular disease?

    PubMed

    Sohani, Zahra N; Li, Ling; Sun, Xin

    2016-07-01

    Incretin-based therapies are normally prescribed to individuals with type 2 diabetes but has recently come under scrutiny due to the possibility of associated pancreatitis. A 2014 systematic review published in the BMJ found no increase risk of acute pancreatitis in adults with type 2 diabetes, as partly evident from the meta-analysis of RCTs (OR=1.11, 95% CI 0.57-2.17). By contrast, a second meta-analysis added 3 large outcome trials in patients with previous cardiovascular disease to the previous 55 RCTs from Li et al. and showed an increased risk in acute pancreatitis. While the discrepancy in result may be due to better quality large trials, as the authors suggest, it is likely that since the large outcome trials investigated patients with cardiovascular disease, the increased risk is present only in this group. PMID:27329019

  16. Engineering the gut for insulin replacement to treat diabetes.

    PubMed

    Mojibian, Majid; Glavas, Maria M; Kieffer, Timothy J

    2016-04-01

    The gut epithelium's large surface area, its direct exposure to ingested nutrients, its vast stem cell population and its immunotolerogenic environment make it an excellent candidate for therapeutic cells to treat diabetes. Thus, several attempts have been made to coax immature gut cells to differentiate into insulin-producing cells by altering the expression patterns of specific transcription factors. Furthermore, because of similarities in enteroendocrine and pancreatic endocrine cell differentiation pathways, other approaches have used genetically engineered enteroendocrine cells to produce insulin in addition to their endogenous secreted hormones. Several studies support the utility of both of these approaches for the treatment of diabetes. Converting a patient's own gut cells into meal-regulated insulin factories in a safe and immunotolerogenic environment is an attractive approach to treat and potentially cure diabetes. Here, we review work on these approaches and indicate where we feel further advancements are required. PMID:27186362

  17. Philosophy with Guts

    ERIC Educational Resources Information Center

    Sherman, Robert R.

    2014-01-01

    Western philosophy, from Plato on, has had the tendency to separate feeling and thought, affect and cognition. This article argues that a strong philosophy (metaphorically, with "guts") utilizes both in its work. In fact, a "complete act of thought" also will include action. Feeling motivates thought, which formulates ideas,…

  18. The Human Gut Microbiota.

    PubMed

    Harmsen, Hermie J M; de Goffau, Marcus C

    2016-01-01

    The microbiota in our gut performs many different essential functions that help us to stay healthy. These functions include vitamin production, regulation of lipid metabolism and short chain fatty acid production as fuel for epithelial cells and regulation of gene expression. There is a very numerous and diverse microbial community present in the gut, especially in the colon, with reported numbers of species that vary between 400 and 1500, for some those we even do not yet have culture representatives.A healthy gut microbiota is important for maintaining a healthy host. An aberrant microbiota can cause diseases of different nature and at different ages ranging from allergies at early age to IBD in young adults. This shows that our gut microbiota needs to be treated well to stay healthy. In this chapter we describe what we consider a healthy microbiota and discuss what the role of the microbiota is in various diseases. Research into these described dysbiosis conditions could lead to new strategies for treatment and/or management of our microbiota to improve health. PMID:27161353

  19. Association between Polycystic Ovary Syndrome and Gut Microbiota

    PubMed Central

    Guo, Yanjie; Qi, Yane; Yang, Xuefei; Zhao, Lihui; Wen, Shu; Liu, Yinhui; Tang, Li

    2016-01-01

    Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats. PMID:27093642

  20. Growth Hormone

    MedlinePlus

    ... the dose of glucose. Growth hormone stimulates the production of insulin-like growth factor-1 (IGF-1) . ... regular intervals for years afterward to monitor GH production and to detect tumor recurrence. Other blood tests ...

  1. Hormone Therapy

    MedlinePlus

    ... based lubricants include petroleum jelly, baby oil, or mineral oil. Oil-based types should not be used ... caused by low levels of these hormones. Hysterectomy: Removal of the uterus. Menopause: The time in a ...

  2. Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats

    PubMed Central

    Pontes, Aiza; Oliveira, Dahienne Ferreira; Ferraz, Emanuelle Baptista; Nascimento, José Hamilton Matheus; Bouskela, Eliete

    2016-01-01

    Background and Aims Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats. Methods and Results We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1) compared with dipeptdyl peptidase-4 (DPP-4) inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet. Conclusion Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders. PMID:26828649

  3. The growth hormone receptor.

    PubMed

    Waters, Michael J

    2016-06-01

    Once thought to be present only in liver, muscle and adipose tissue, the GH receptor is now known to be ubiquitously distributed, in accord with the many pleiotropic actions of GH. These include the regulation of metabolism, postnatal growth, cognition, immune, cardiac and renal systems and gut function. GH exerts these actions primarily through alterations in gene expression, initiated by activation of its membrane receptor and the resultant activation of the associated JAK2 (Janus kinase 2) and Src family kinases. Receptor activation involves hormone initiated movements within a receptor homodimer, rather than simple receptor dimerization. We have shown that binding of the hormone realigns the orientation of the two receptors both by relative rotation and by closer apposition just above the cell membrane. This is a consequence of the asymmetric placement of the binding sites on the hormone. Binding results in a conversion of parallel receptor transmembrane domains into a rotated crossover orientation, which produces separation of the lower part of the transmembrane helices. Because the JAK2 is bound to the Box1 motif proximal to the inner membrane, receptor activation results in separation of the two associated JAK2s, and in particular the removal of the inhibitory pseudokinase domain from the kinase domain of the other JAK2 (and vice versa). This brings the two kinase domains into position for trans-activation and initiates tyrosine phosphorylation of the receptor cytoplasmic domain and other substrates such as STAT5, the key transcription factor mediating most genomic actions of GH. There are a limited number of genomic actions initiated by the Src kinase family member which also associates with the upper cytoplasmic domain of the receptor, including important immune regulatory actions to dampen exuberant innate immune activation of cells involved in transplant rejection. These findings offer insights for developing specific receptor antagonists which may be

  4. Endocannabinoids in the Gut

    PubMed Central

    DiPatrizio, Nicholas V.

    2016-01-01

    Cannabis has been used medicinally for centuries to treat a variety of disorders, including those associated with the gastrointestinal tract. The discovery of our bodies’ own “cannabis-like molecules” and associated receptors and metabolic machinery – collectively called the endocannabinoid system – enabled investigations into the physiological relevance for the system, and provided the field with evidence of a critical function for this endogenous signaling pathway in health and disease. Recent investigations yield insight into a significant participation for the endocannabinoid system in the normal physiology of gastrointestinal function, and its possible dysfunction in gastrointestinal pathology. Many gaps, however, remain in our understanding of the precise neural and molecular mechanisms across tissue departments that are under the regulatory control of the endocannabinoid system. This review highlights research that reveals an important – and at times surprising – role for the endocannabinoid system in the control of a variety of gastrointestinal functions, including motility, gut-brain mediated fat intake and hunger signaling, inflammation and gut permeability, and dynamic interactions with gut microbiota. PMID:27413788

  5. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  6. Assessment of incretins in oral glucose and lipid tolerance tests may be indicative in the diagnosis of metabolic syndrome aggravation.

    PubMed

    Kiec-Klimczak, M; Malczewska-Malec, M; Razny, U; Zdzienicka, A; Gruca, A; Goralska, J; Pach, D; Gilis-Januszewska, A; Dembinska-Kiec, A; Hubalewska-Dydejczyk, A

    2016-04-01

    Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P < 0.001) within each of the investigated groups. In patients with the highest fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin

  7. Gut Microbiota and Metabolic Disorders.

    PubMed

    Hur, Kyu Yeon; Lee, Myung-Shik

    2015-06-01

    Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

  8. Roles of the Gut in Glucose Homeostasis.

    PubMed

    Holst, Jens Juul; Gribble, Fiona; Horowitz, Michael; Rayner, Chris K

    2016-06-01

    The gastrointestinal tract plays a major role in the regulation of postprandial glucose profiles. Gastric emptying is a highly regulated process, which normally ensures a limited and fairly constant delivery of nutrients and glucose to the proximal gut. The subsequent digestion and absorption of nutrients are associated with the release of a set of hormones that feeds back to regulate subsequent gastric emptying and regulates the release of insulin, resulting in downregulation of hepatic glucose production and deposition of glucose in insulin-sensitive tissues. These remarkable mechanisms normally keep postprandial glucose excursions low, regardless of the load of glucose ingested. When the regulation of emptying is perturbed (e.g., pyloroplasty, gastric sleeve or gastric bypass operation), postprandial glycemia may reach high levels, sometimes followed by profound hypoglycemia. This article discusses the underlying mechanisms. PMID:27222546

  9. GUTs and TOEs

    SciTech Connect

    Lincoln, Don

    2015-01-20

    Albert Einstein said that what he wanted to know was “God’s thoughts,” which is a metaphor for the ultimate and most basic rules of the universe. Once known, all other phenomena would then be a consequence of these simple rules. While modern science is far from that goal, we have some thoughts on how this inquiry might unfold. In this video, Fermilab’s Dr. Don Lincoln tells what we know about GUTs (grand unified theories) and TOEs (theories of everything).

  10. The giant panda gut microbiome.

    PubMed

    Wei, Fuwen; Wang, Xiao; Wu, Qi

    2015-08-01

    Giant pandas (Ailuropoda melanoleuca) are bamboo specialists that evolved from carnivores. Their gut microbiota probably aids in the digestion of cellulose and this is considered an example of gut microbiota adaptation to a bamboo diet. However, this issue remains unresolved and further functional and compositional studies are needed. PMID:26143242

  11. Metagenomic surveys of gut microbiota.

    PubMed

    Mandal, Rahul Shubhra; Saha, Sudipto; Das, Santasabuj

    2015-06-01

    Gut microbiota of higher vertebrates is host-specific. The number and diversity of the organisms residing within the gut ecosystem are defined by physiological and environmental factors, such as host genotype, habitat, and diet. Recently, culture-independent sequencing techniques have added a new dimension to the study of gut microbiota and the challenge to analyze the large volume of sequencing data is increasingly addressed by the development of novel computational tools and methods. Interestingly, gut microbiota maintains a constant relative abundance at operational taxonomic unit (OTU) levels and altered bacterial abundance has been associated with complex diseases such as symptomatic atherosclerosis, type 2 diabetes, obesity, and colorectal cancer. Therefore, the study of gut microbial population has emerged as an important field of research in order to ultimately achieve better health. In addition, there is a spontaneous, non-linear, and dynamic interaction among different bacterial species residing in the gut. Thus, predicting the influence of perturbed microbe-microbe interaction network on health can aid in developing novel therapeutics. Here, we summarize the population abundance of gut microbiota and its variation in different clinical states, computational tools available to analyze the pyrosequencing data, and gut microbe-microbe interaction networks. PMID:26184859

  12. Metagenomic Surveys of Gut Microbiota

    PubMed Central

    Mandal, Rahul Shubhra; Saha, Sudipto; Das, Santasabuj

    2015-01-01

    Gut microbiota of higher vertebrates is host-specific. The number and diversity of the organisms residing within the gut ecosystem are defined by physiological and environmental factors, such as host genotype, habitat, and diet. Recently, culture-independent sequencing techniques have added a new dimension to the study of gut microbiota and the challenge to analyze the large volume of sequencing data is increasingly addressed by the development of novel computational tools and methods. Interestingly, gut microbiota maintains a constant relative abundance at operational taxonomic unit (OTU) levels and altered bacterial abundance has been associated with complex diseases such as symptomatic atherosclerosis, type 2 diabetes, obesity, and colorectal cancer. Therefore, the study of gut microbial population has emerged as an important field of research in order to ultimately achieve better health. In addition, there is a spontaneous, non-linear, and dynamic interaction among different bacterial species residing in the gut. Thus, predicting the influence of perturbed microbe–microbe interaction network on health can aid in developing novel therapeutics. Here, we summarize the population abundance of gut microbiota and its variation in different clinical states, computational tools available to analyze the pyrosequencing data, and gut microbe–microbe interaction networks. PMID:26184859

  13. Gut Microbiota: The Brain Peacekeeper.

    PubMed

    Mu, Chunlong; Yang, Yuxiang; Zhu, Weiyun

    2016-01-01

    Gut microbiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gut microbiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota-gut-brain axis and the role of microbiota as a "peacekeeper" in the brain health. Here, we review recent discoveries on the role of the gut microbiota in central nervous system-related diseases. We also discuss the emerging concept of the bidirectional regulation by the circadian rhythm and gut microbiota, and the potential role of the epigenetic regulation in neuronal cell function. Microbiome studies are also highlighted as crucial in the development of targeted therapies for neurodevelopmental disorders. PMID:27014255

  14. Hormone impostors

    SciTech Connect

    Colborn, T.; Dumanoski, D.; Myers, J.P.

    1997-01-01

    This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.

  15. Glucagon-like peptide 2 therapy reduces negative effects of diarrhea on calf gut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Damage to the intestinal epithelium caused by diarrhea reduces nutrient absorption and growth rate, and may have long-term effects on the young animal. Glucagon-like peptide 2 (GLP-2) is an intestinotropic hormone that improves gut integrity and nutrient absorption, and has antioxidant effects in th...

  16. Pancreatitis with pancreatic tail swelling associated with incretin-based therapies detected radiologically in two cases of diabetic patients with end-stage renal disease.

    PubMed

    Nakata, Hirosuke; Sugitani, Seita; Yamaji, Shuhei; Otsu, Satoko; Higashi, Yoshihito; Ohtomo, Yumiko; Inoue, Gen

    2012-01-01

    We herein report two cases of pancreatitis associated with incretin-based therapies in end-stage renal disease (ESRD) patients undergoing dialysis. A 75-year-old woman with a history of liraglutide use and a 68-year-old man with a history of vildagliptin use both presented with nausea. They showed elevated levels of pancreatic enzymes and pancreatic tail swelling on CT. Their symptoms improved after discontinuing the drugs. In the absence of any obvious secondary causes of pancreatitis, we believe that the pancreatitis observed in these cases was associated with the incretin-based therapies. Few reports have been published on the safety and efficacy of incretin-based therapies in ESRD patients, and it remains uncertain whether the changes in the pancreas observed in the present cases are characteristic of ESRD patients. PMID:23124148

  17. Hormone Health Network

    MedlinePlus

    International Resource Center Online Store Pacientes y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types of Hormones Brainy Hormones What Do Hormones Do? Healthy Living ...

  18. Adipocytokines, gut hormones and growth factors in anorexia nervosa.

    PubMed

    Kowalska, Irina; Karczewska-Kupczewska, Monika; Strączkowski, Marek

    2011-09-18

    Anorexia nervosa is a complex eating disorder of unknown etiology which affects adolescent girls and young women and leads to chronic malnutrition. Clinical manifestations of prolonged semistarvation include a variety of physical features and psychiatric disorders. The study of different biological factors involved in the pathophysiology of anorexia nervosa is an area of active interest. In this review we have described the role of adipocytokines, neurotrophins, peptides of the gastrointestinal system and growth factors in appetite regulation, energy balance and insulin sensitivity in anorexia nervosa patients. PMID:21699889

  19. [Effect of gastrectomy on release of gut hormones].

    PubMed

    Misumi, A; Harada, K; Mizumoto, S; Yoshinaka, I; Maeda, M; Nakashima, Y; Ogawa, M

    1991-09-01

    We investigated the effect of gastrectomy on the digestive system in 87 postoperative long-term survivors under test meal or egg yolk load. After test meal, gastrin and secretin responses were decreased in each of groups of proximal gastrectomy (PG), distal gastrectomy with Billroth-I (DG-B1), that with Billroth-II (DG-B2), total gastrectomy with interposition (TG-I), and that with Roux-Y (TG-RY). However, sufficient acid-secretors after partial gastrectomy showed secretin responses comparable to controls. Furthermore, cases of total gastrectomy given betain-hydrochloride with test meal increased secretin responses. Serum glucose response was higher in the TG-RY group while insulin response was high in the TG-RY and DG-B2 groups, compared with controls. GLI response was high in all groups compared with controls. Postgastrectomy gallstone occurred in 11.6%. Yolk-induced contraction of the gallbladder was decreased, and CCK release increased, for several years postoperatively. Gallbladder contraction with CCK was reduced for one year postoperatively. The contraction was reduced in persons with gallstone than those without it. This study shows that the digestive function after gastrectomy depends on acidification and duodenal passage of food, and that reduced contraction with CCK plays an important role in hypokinesis of the gallbladder. PMID:1944181

  20. Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance

    PubMed Central

    Carvalho, Bruno Melo; Abdalla Saad, Mario Jose

    2013-01-01

    Obesity is the main condition that is correlated with the appearance of insulin resistance, which is the major link among its comorbidities, such as type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. Obesity affects a large number of individuals worldwide; it degrades human health and quality of life. Here, we review the role of the gut microbiota in the pathophysiology of obesity and type 2 diabetes, which is promoted by a bacterial diversity shift mediated by overnutrition. Whole bacteria, their products, and metabolites undergo increased translocation through the gut epithelium to the circulation due to degraded tight junctions and the consequent increase in intestinal permeability that culminates in inflammation and insulin resistance. Several strategies focusing on modulation of the gut microbiota (antibiotics, probiotics, and prebiotics) are being experimentally employed in metabolic derangement in order to reduce intestinal permeability, increase the production of short chain fatty acids and anorectic gut hormones, and promote insulin sensitivity to counteract the inflammatory status and insulin resistance found in obese individuals. PMID:23840101

  1. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases.

    PubMed

    Brown, J Mark; Hazen, Stanley L

    2015-01-01

    The human gastrointestinal tract is home to trillions of bacteria, which vastly outnumber host cells in the body. Although generally overlooked in the field of endocrinology, gut microbial symbionts organize to form a key endocrine organ that converts nutritional cues from the environment into hormone-like signals that impact both normal physiology and chronic disease in the human host. Recent evidence suggests that several gut microbial-derived products are sensed by dedicated host receptor systems to alter cardiovascular disease (CVD) progression. In fact, gut microbial metabolism of dietary components results in the production of proatherogenic circulating factors that act through a meta-organismal endocrine axis to impact CVD risk. Whether pharmacological interventions at the level of the gut microbial endocrine organ will reduce CVD risk is a key new question in the field of cardiovascular medicine. Here we discuss the opportunities and challenges that lie ahead in targeting meta-organismal endocrinology for CVD prevention. PMID:25587655

  2. The Gut Microbial Endocrine Organ: Bacterially-Derived Signals Driving Cardiometabolic Diseases

    PubMed Central

    Brown, J. Mark; Hazen, Stanley L.

    2015-01-01

    The human gastrointestinal tract is home to trillions of bacteria, which vastly outnumber host cells in the body. Although generally overlooked in the field of endocrinology, gut microbial symbionts organize to form a key endocrine organ that convert nutritional cues from the environment into hormone-like signals that impact both normal physiology and chronic disease in the human host. Recent evidence suggests that several gut microbial-derived products are sensed by dedicated host receptor systems to alter cardiovascular disease (CVD) progression. In fact, gut microbial metabolism of dietary components results in the production of proatherogenic circulating factors that act through a meta-organismal endocrine axis to impact CVD risk. Whether pharmacological interventions at the level of the gut microbial endocrine organ will reduce CVD risk is a key new question in the field of cardiovascular medicine. Here we discuss the opportunities and challenges that lie ahead in targeting meta-organismal endocrinology for CVD prevention. PMID:25587655

  3. Gut microbiota and metabolic syndrome

    PubMed Central

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-01-01

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

  4. Flipped GUT inflation

    SciTech Connect

    Ellis, John; Gonzalo, Tomás E.; Harz, Julia; Huang, Wei-Chih

    2015-03-23

    We analyse the prospects for constructing hybrid models of inflation that provide a dynamical realisation of the apparent closeness between the supersymmetric GUT scale and the possible scale of cosmological inflation. In the first place, we consider models based on the flipped SU(5)×U(1) gauge group, which has no magnetic monopoles. In one model, the inflaton is identified with a sneutrino field, and in the other model it is a gauge singlet. In both cases we find regions of the model parameter spaces that are compatible with the experimental magnitudes of the scalar perturbations, A{sub s}, and the tilt in the scalar perturbation spectrum, n{sub s}, as well as with an indicative upper limit on the tensor-to-scalar perturbation ratio, r. We also discuss embeddings of these models into SO(10), which is broken at a higher scale so that its monopoles are inflated away.

  5. A fatty gut feeling

    PubMed Central

    Piomelli, Daniele

    2013-01-01

    The absorptive epithelium of the proximal small intestine converts oleic acid released during fat digestion into oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α). OEA interacts with this receptor to cause a state of satiety characterized by prolonged inter-meal intervals and reduced feeding frequency. The two main branches of the autonomic nervous system, sympathetic and parasympathetic, contribute to this effect: the former by enabling OEA mobilization in the gut and the latter by relaying the OEA signal to brain structures, such as the hypothalamus, that are involved in feeding regulation. OEA signaling may be a key component of the physiological system devoted to the monitoring of dietary fat intake, and its dysfunction might contribute to overweight and obesity. PMID:23567058

  6. Development and physiology of the rumen and the lower gut: Targets for improving gut health.

    PubMed

    Steele, Michael A; Penner, Greg B; Chaucheyras-Durand, Frédérique; Guan, Le Luo

    2016-06-01

    The gastrointestinal epithelium of the dairy cow and calf faces the challenge of protecting the host from the contents of the luminal milieu while controlling the absorption and metabolism of nutrients. Adaptations of the gastrointestinal tract play an important role in animal energetics as the portal-drained viscera accounts for 20% of the total oxygen consumption of the ruminant. The mechanisms that govern growth and barrier function of the gastrointestinal epithelium have received particular attention over the past decade, especially with advancements in molecular-based techniques, such as microarrays and next-generation DNA sequencing. The rumen has been the focal point of dairy cow and calf nutritional physiology research, whereas the lower gut has received less attention. Three key areas that require discovery-based and applied research include (1) early-life intestinal gut barrier function and growth; (2) how the weaning transition affects function of the rumen and intestine; and (3) gastrointestinal adaptations during the transition to high-energy diets in early lactation. In dairy nutrition, nutrients are seen not only as metabolic substrates, but also as signals that can alter gastrointestinal growth and barrier function. Nutrients have been shown to affect epithelial cell gene expression directly and, in concert with insulin-like growth factor, growth hormone, and glucagon-like peptide 2, play a pivotal role in gut tissue growth. The latest research suggests that ruminal and intestinal barrier function is compromised during the preweaning phase, at weaning, and in early lactation. Gastrointestinal barrier function is influenced by the presence of metabolites, such as butyrate, the resident microbiota, and the microbes provided in feed. In the first studies that investigated barrier function in cows and calves, it was determined that the expression of genes encoding tight junction proteins, such as claudins, occludins, and desmosomal cadherins, are

  7. The gut microbiome.

    PubMed

    Actis, Giovanni C

    2014-01-01

    Since the discovery and use of the microscope in the 17(th) century, we know that we host trillions of micro-organisms mostly in the form of bacteria indwelling the "barrier organs" skin, gut, and airways. They exert regulatory functions, are in a continuous dialogue with the intestinal epithelia, influence energy handling, produce nutrients, and may cause diabetes and obesity. The human microbiome has developed by modulating or avoiding inflammatory responses; the host senses bacterial presence through cell surface sensors (the Toll-like receptors) as well as by refining mucous barriers as passive defense mechanisms. The cell density and composition of the microbiome are variable and multifactored. The way of delivery establishes the type of initial flora; use of antibiotics is another factor; diet composition after weaning will shape the adult's microbiome composition, depending on the subject's life-style. Short-chain fatty acids participate in the favoring action exerted by microbiome in the pathogenesis of type-2 diabetes and obesity. Clinical observation has pinpointed a sharp rise of various dysimmune conditions in the last decades, including IBD and rheumatoid arthritis, changes that outweigh the input of simple heritability. It is nowadays proposed that the microbiome, incapable to keep up with the changes of our life-style and feeding sources in the past few decades might have contributed to these immune imbalances, finding itself inadequate to handle the changed gut environment. Another pathway to pathology is the rise of directly pathogenic phyla within a given microbiome: growth of adherent E. coli, of C. concisus, and of C. jejuni, might be examples of causes of local enteropathy, whereas the genus Prevotella copri is now suspected to be linked to rise of arthritic disorders. Inflammasomes are required to shape a non colitogenic flora. Treatment of IBD and infectious enteritides by the use of fecal transplant is warranted by this knowledge. PMID

  8. Links between diet, gut microbiota composition and gut metabolism.

    PubMed

    Flint, Harry J; Duncan, Sylvia H; Scott, Karen P; Louis, Petra

    2015-02-01

    The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches. PMID:25268552

  9. GUTs and supersymmetric GUTs in the very early universe

    SciTech Connect

    Ellis, J.

    1982-10-01

    This talk is intended as background material for many of the other talks treating the possible applications of GUTs to the very early universe. I start with a review of the present theoretical and phenomenological status of GUTs before going on to raise some new issues for their prospective cosmological applications which arise in supersymmetric (susy) GUTs. The first section is an update on conventional GUTs, which is followed by a reminder of some of the motivations for going supersymmetric. There then follows a simple primer on susy and a discussion of the structure and phenomenology of simple sysy GUTs. Finally we come to the cosmological issues, including problems arising from the degeneracy of susy minima, baryosynthesis and supersymmetric inflation, the possibility that gravity is an essential complication in constructing susy GUTs and discussing their cosmology, and the related question of what mass range is allowed for the gravitino. Several parts of this write-up contain new material which has emerged either during the Workshop or subsequently. They are included here for completeness and the convenience of the prospective reader. Wherever possible, these anachronisms will be flagged so as to keep straight the historical record.

  10. Gut Microbiota: The Brain Peacekeeper

    PubMed Central

    Mu, Chunlong; Yang, Yuxiang; Zhu, Weiyun

    2016-01-01

    Gut microbiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gut microbiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota–gut–brain axis and the role of microbiota as a “peacekeeper” in the brain health. Here, we review recent discoveries on the role of the gut microbiota in central nervous system-related diseases. We also discuss the emerging concept of the bidirectional regulation by the circadian rhythm and gut microbiota, and the potential role of the epigenetic regulation in neuronal cell function. Microbiome studies are also highlighted as crucial in the development of targeted therapies for neurodevelopmental disorders. PMID:27014255

  11. Gut Microbiome and Colorectal Adenomas

    PubMed Central

    Dulal, Santosh; Keku, Temitope O.

    2015-01-01

    The trillions of bacteria that naturally reside in the human gut collectively constitute the complex system known the gut microbiome, a vital player for the host’s homeostasis and health. However, there is mounting evidence that dysbiosis, a state of pathological imbalance in the gut microbiome is present in many disease states. In this review, we present recent insights concerning the gut microbiome’s contribution to the development of colorectal adenomas and the subsequent progression to colorectal cancer (CRC). In the United States alone, CRC is the second leading cause of cancer deaths. As a result, there is a high interest in identifying risk factors for adenomas, which are intermediate precursors to CRC. Recent research on CRC and the microbiome suggest that modulation of the gut bacterial composition and structure may be useful in preventing adenomas and CRC. We highlight the known risk factors for colorectal adenomas and the potential mechanisms by which microbial dysbiosis may contribute to the etiology of CRC. We also underscore novel findings from recent studies on the gut microbiota and colorectal adenomas along with current knowledge gaps. Understanding the microbiome may provide promising new directions towards novel diagnostic tools, biomarkers, and therapeutic interventions for CRC. PMID:24855012

  12. Gut Microbes, Diet, and Cancer

    PubMed Central

    Hullar, Meredith A. J.; Burnett-Hartman, Andrea N.

    2014-01-01

    An expanding body of evidence supports a role for gut microbes in the etiology of cancer. Previously, the focus was on identifying individual bacterial species that directly initiate or promote gastrointestinal malignancies; however, the capacity of gut microbes to influence systemic inflammation and other downstream pathways suggests that the gut microbial community may also affect risk of cancer in tissues outside of the gastrointestinal tract. Functional contributions of the gut microbiota that may influence cancer susceptibility in the broad sense include (1) harvesting otherwise inaccessible nutrients and/or sources of energy from the diet (i.e., fermentation of dietary fibers and resistant starch); (2) metabolism of xenobiotics, both potentially beneficial or detrimental (i.e., dietary constituents, drugs, carcinogens, etc.); (3) renewal of gut epithelial cells and maintenance of mucosal integrity; and (4) affecting immune system development and activity. Understanding the complex and dynamic interplay between the gut microbiome, host immune system, and dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention and treatment strategies. PMID:24114492

  13. Gut dysfunction in Parkinson's disease.

    PubMed

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-07-01

    Early involvement of gut is observed in Parkinson's disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  14. Probiotics, gut microbiota and health.

    PubMed

    Butel, M-J

    2014-01-01

    The human gut is a huge complex ecosystem where microbiota, nutrients, and host cells interact extensively, a process crucial for the gut homeostasis and host development with a real partnership. The various bacterial communities that make up the gut microbiota have many functions including metabolic, barrier effect, and trophic functions. Hence, any dysbiosis could have negative consequences in terms of health and many diseases have been associated to impairment of the gut microbiota. These close relationships between gut microbiota, health, and disease, have led to great interest in using probiotics (i.e. live micro-organisms), or prebiotics (i.e. non-digestible substrates) to positively modulate the gut microbiota to prevent or treat some diseases. This review focuses on probiotics, their mechanisms of action, safety, and major health benefits. Health benefits remain to be proven in some indications, and further studies on the best strain(s), dose, and algorithm of administration to be used are needed. Nevertheless, probiotic administration seems to have a great potential in terms of health that justifies more research. PMID:24290962

  15. Gut microbes, diet, and cancer.

    PubMed

    Hullar, Meredith A J; Burnett-Hartman, Andrea N; Lampe, Johanna W

    2014-01-01

    An expanding body of evidence supports a role for gut microbes in the etiology of cancer. Previously, the focus was on identifying individual bacterial species that directly initiate or promote gastrointestinal malignancies; however, the capacity of gut microbes to influence systemic inflammation and other downstream pathways suggests that the gut microbial community may also affect risk of cancer in tissues outside of the gastrointestinal tract. Functional contributions of the gut microbiota that may influence cancer susceptibility in the broad sense include (1) harvesting otherwise inaccessible nutrients and/or sources of energy from the diet (i.e., fermentation of dietary fibers and resistant starch); (2) metabolism of xenobiotics, both potentially beneficial or detrimental (i.e., dietary constituents, drugs, carcinogens, etc.); (3) renewal of gut epithelial cells and maintenance of mucosal integrity; and (4) affecting immune system development and activity. Understanding the complex and dynamic interplay between the gut microbiome, host immune system, and dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention and treatment strategies. PMID:24114492

  16. Gut dysfunction in Parkinson's disease

    PubMed Central

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-01-01

    Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  17. Gut Microbiota and Hepatocellular Carcinoma

    PubMed Central

    Tao, Xuemei; Wang, Ning; Qin, Wenxin

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a common complication of liver diseases such as those related to viral hepatitis and liver cirrhosis. The gut-liver axis is gaining increasing attention as a key pathophysiological mechanism responsible for the progression of HCC. Here, we will review the data from the published literature to address the association between HCC and gut microbiota. Summary The presence of high levels of endotoxemia in the blood results in portal hypertension and ensuing hepatocyte damage, thus leading to the development of HCC. Probiotics can be used to treat or prevent the progression of HCC, because they may decrease the counts of gut microbiota and thus improve the endotoxemia. Key Message Increased bacterial translocation can result in endotoxemia, which may play a critical role in the progression of HCC. Modulation of the gut microbiota by probiotics may represent a new avenue for therapeutic intervention in HCC. Practical Implications Breakdown in intestinal barrier function and bacterial overgrowth are main events in the development of HCC. When the intestinal barrier function is disrupted, large amounts of bacterial products can enter the liver and induce inflammation through their receptors, leading to liver diseases. Altering the gut microflora has been proposed as an adjunctive therapy to reduce bacterial translocation and prevent progression of HCC. The purpose of this review is to discuss the relationship between gut microbiota and HCC in both pathogenesis and treatment by probiotics. PMID:26673641

  18. Nutrigenomics and gut health.

    PubMed

    Ferguson, Lynnette R; Shelling, Andrew N; Lauren, Denis; Heyes, Julian A; McNabb, Warren C

    2007-09-01

    Recognition of the interplay between genes and diet in development of disease and for maintenance of optimal metabolism has led to nutrigenomic or nutrigenetic approaches to personalising or individualising nutrition, with the potential of preventing, delaying, or reducing the symptoms of chronic diseases. Some of the development work has focussed on cardiovascular disease or type II diabetes mellitus, where various groups have identified potential diet-gene interactions. However, the available studies also emphasise the exponential increase in numbers of subjects necessary to recruit for clinical evaluation if we are to successfully provide informative high-dimensional datasets of genetic, nutrient, metabolomic (clinical), and other variables. There is also a significant bioinformatics challenge to analyze these. To add to the complexity, many of the pioneering studies had assumed that single nucleotide polymorphisms (SNPs) were the main source of human variability, but an increasing evidence base suggests the importance of more subtle gene regulatory mechanisms, including copy number variants. As an example, the risk of Inflammatory Bowel Disease (IBD) is associated with the inheritance of a number of contributory SNPs as well as with copy number variants of certain other genes. The variant forms of genes often result in disruptions to bacterial homeostasis mechanisms or to signal transduction of the intestinal epithelial cell of the host, and thereby to altered intestinal barrier function, and/or adaptive immune responses. The human gut microbiota is altered in individuals suffering from disorders such as IBD, and probiotic or prebiotic therapies or elemental diets may be beneficial to a high proportion of individuals through modifying the gut microbiota, and also modulating immune responses. New putative foods or dietary therapies may be identified through novel tissue culture screens, followed by further testing with in vivo animal models of human disease. A

  19. Gastrointestinal hormones.

    PubMed

    Straus, E

    2000-01-01

    Solomon A. Berson, M.D., the first Murray M. Rosenberg Professor and Chair of the Department of Medicine at Mount Sinai from 1968 until his death in 1972, and Rosalyn S. Yalow, Ph.D., 1977 Nobel Laureate in Medicine or Physiology and Solomon A. Berson Distinguished Professor-at-Large, brought meticulous quantitation and new vistas to all of clinical medicine and biomedical science through the application of their technique of radioimmunoassay. I was fortunate to know and work with them for many years. In 1972, while I was an NIH Fellow in gastroenterology at Mount Sinai, Dr. Berson suggested that I pursue my research in their laboratory at the Bronx Veterans Administration Hospital. Dr. Berson died one month after I began my research in the Bronx. Yalow and Berson had already discovered big gastrin (G-34), but much work with gastrin remained to be done. Challenging work with secretin, cholecystokinin, and a host of other gut peptides, would keep the Mount Sinai group at the forefront of this exciting field. PMID:10679142

  20. Metabolomic insights into the intricate gut microbial–host interaction in the development of obesity and type 2 diabetes

    PubMed Central

    Palau-Rodriguez, Magali; Isabel Queipo-Ortuño, Maria; Urpi-Sarda, Mireia; Tinahones, Francisco J.; Andres-Lacueva, Cristina

    2015-01-01

    Gut microbiota has recently been proposed as a crucial environmental factor in the development of metabolic diseases such as obesity and type 2 diabetes, mainly due to its contribution in the modulation of several processes including host energy metabolism, gut epithelial permeability, gut peptide hormone secretion, and host inflammatory state. Since the symbiotic interaction between the gut microbiota and the host is essentially reflected in specific metabolic signatures, much expectation is placed on the application of metabolomic approaches to unveil the key mechanisms linking the gut microbiota composition and activity with disease development. The present review aims to summarize the gut microbial–host co-metabolites identified so far by targeted and untargeted metabolomic studies in humans, in association with impaired glucose homeostasis and/or obesity. An alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins (i.e., niacin), purines, and phenolic compounds has been associated so far with the obese or diabese phenotype, in respect to healthy controls. Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown. Despite the scarcity of the metabolomic studies currently available on the microbial–host crosstalk, the data-driven results largely confirmed findings independently obtained from in vitro and animal model studies, putting forward the mechanisms underlying the implication of a dysfunctional gut microbiota in the development of metabolic disorders. PMID:26579078

  1. Growth hormone suppression test

    MedlinePlus

    The growth hormone suppression test determines whether growth hormone production is being suppressed by high blood sugar. ... away. The lab measures the glucose and growth hormone (GH) levels in each sample.

  2. Hormone Replacement Therapy

    MedlinePlus

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  3. Growth hormone test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003706.htm Growth hormone test To use the sharing features on this page, please enable JavaScript. The growth hormone test measures the amount of growth hormone in ...

  4. Growth hormone suppression test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  5. Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome

    PubMed Central

    Parnell, Jill A.; Reimer, Raylene A.

    2013-01-01

    Prebiotic fibers are non-digestible carbohydrates that promote the growth of beneficial bacteria in the gut. Prebiotic consumption may benefit obesity and associated co-morbidities by improving or normalizing the dysbiosis of the gut microbiota. We evaluated the dose response to a prebiotic diet on the gut microbiota, body composition and obesity associated risk factors in lean and genetically obese rats. Prebiotic fibers increased Firmicutes and decreased Bacteroidetes, a profile often associated with a leaner phenotype. Bifidobacteria and Lactobacillus numbers also increased. Changes in the gut microbiota correlated with energy intake, glucose, insulin, satiety hormones, and hepatic cholesterol and triglyceride accumulation. Here we provide a comprehensive analysis evaluating the results through the lens of the gut microbiota. Salient, new developments impacting the interpretation and significance of our data are discussed. We propose that prebiotic fibers have promise as a safe and cost-effective means of modulating the gut microbiota to promote improved host:bacterial interactions in obesity and insulin resistance. Human clinical trials should be undertaken to confirm these effects. PMID:22555633

  6. Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease

    PubMed Central

    Sanchez, Ramiro A; Sanabria, Hugo; de los Santos, Cecilia; Ramirez, Agustin J

    2015-01-01

    Hyperglycemia is associated with an increased risk of cardiovascular disease, and the consequences of intensive therapy may depend on the mechanism of the anti-diabetic agent(s) used to achieve a tight control. In animal models, stable analogues of glucagon-like peptide-1 (GLP-1) were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion. In a similar way, dipeptidyl peptidase IV (DPP-IV) showed to have favorable effects in animal models of ischemia/reperfusion. This could be due to the fact that DPP-IV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide, but they also decreased the degradation of several vasoactive peptides. Preclinical data for GLP-1, its derivatives and inhibitors of the DPP-IV enzyme degradation suggests that these agents may be able to, besides controlling glycaemia, induce cardio-protective and vasodilator effects. Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies, many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints. For this reason, long-term trials searching for positive cardiovascular effects are now in process, such as the CAROLINA and CARMELINA trials, which are supported by small pilot studies performed in humans (and many more animal studies) with incretin-based therapies. On the other hand, selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes. However, it is quite early to draw conclusions, since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing. In this review, we will analyze the mechanisms underlying the cardiovascular effects of incretins and, at the same time, we will present a critical position about the real

  7. Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease.

    PubMed

    Sanchez, Ramiro A; Sanabria, Hugo; de Los Santos, Cecilia; Ramirez, Agustin J

    2015-09-10

    Hyperglycemia is associated with an increased risk of cardiovascular disease, and the consequences of intensive therapy may depend on the mechanism of the anti-diabetic agent(s) used to achieve a tight control. In animal models, stable analogues of glucagon-like peptide-1 (GLP-1) were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion. In a similar way, dipeptidyl peptidase IV (DPP-IV) showed to have favorable effects in animal models of ischemia/reperfusion. This could be due to the fact that DPP-IV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide, but they also decreased the degradation of several vasoactive peptides. Preclinical data for GLP-1, its derivatives and inhibitors of the DPP-IV enzyme degradation suggests that these agents may be able to, besides controlling glycaemia, induce cardio-protective and vasodilator effects. Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies, many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints. For this reason, long-term trials searching for positive cardiovascular effects are now in process, such as the CAROLINA and CARMELINA trials, which are supported by small pilot studies performed in humans (and many more animal studies) with incretin-based therapies. On the other hand, selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes. However, it is quite early to draw conclusions, since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing. In this review, we will analyze the mechanisms underlying the cardiovascular effects of incretins and, at the same time, we will present a critical position about the real

  8. Adverse events associated with incretin-based drugs in Japanese spontaneous reports: a mixed effects logistic regression model

    PubMed Central

    Narushima, Daichi; Kawasaki, Yohei; Takamatsu, Shoji

    2016-01-01

    Background: Spontaneous Reporting Systems (SRSs) are passive systems composed of reports of suspected Adverse Drug Events (ADEs), and are used for Pharmacovigilance (PhV), namely, drug safety surveillance. Exploration of analytical methodologies to enhance SRS-based discovery will contribute to more effective PhV. In this study, we proposed a statistical modeling approach for SRS data to address heterogeneity by a reporting time point. Furthermore, we applied this approach to analyze ADEs of incretin-based drugs such as DPP-4 inhibitors and GLP-1 receptor agonists, which are widely used to treat type 2 diabetes. Methods: SRS data were obtained from the Japanese Adverse Drug Event Report (JADER) database. Reported adverse events were classified according to the MedDRA High Level Terms (HLTs). A mixed effects logistic regression model was used to analyze the occurrence of each HLT. The model treated DPP-4 inhibitors, GLP-1 receptor agonists, hypoglycemic drugs, concomitant suspected drugs, age, and sex as fixed effects, while the quarterly period of reporting was treated as a random effect. Before application of the model, Fisher’s exact tests were performed for all drug-HLT combinations. Mixed effects logistic regressions were performed for the HLTs that were found to be associated with incretin-based drugs. Statistical significance was determined by a two-sided p-value <0.01 or a 99% two-sided confidence interval. Finally, the models with and without the random effect were compared based on Akaike’s Information Criteria (AIC), in which a model with a smaller AIC was considered satisfactory. Results: The analysis included 187,181 cases reported from January 2010 to March 2015. It showed that 33 HLTs, including pancreatic, gastrointestinal, and cholecystic events, were significantly associated with DPP-4 inhibitors or GLP-1 receptor agonists. In the AIC comparison, half of the HLTs reported with incretin-based drugs favored the random effect, whereas HLTs

  9. Gut microbiota and hepatic encephalopathy.

    PubMed

    Dhiman, Radha K

    2013-06-01

    There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE. PMID:23463489

  10. Gut immunity in Lepidopteran insects.

    PubMed

    Wu, Kai; Yang, Bing; Huang, Wuren; Dobens, Leonard; Song, Hongsheng; Ling, Erjun

    2016-11-01

    Lepidopteran insects constitute one of the largest fractions of animals on earth, but are considered pests in their relationship with man. Key to the success of this order of insects is its ability to digest food and absorb nutrition, which takes place in the midgut. Because environmental microorganisms can easily enter Lepidopteran guts during feeding, the innate immune response guards against pathogenic bacteria, virus and microsporidia that can be devoured with food. Gut immune responses are complicated by both resident gut microbiota and the surrounding peritrophic membrane and are distinct from immune responses in the body cavity, which depend on the function of the fat body and hemocytes. Due to their relevance to agricultural production, studies of Lepidopteran insect midgut and immunity are receiving more attention, and here we summarize gut structures and functions, and discuss how these confer immunity against different microorganisms. It is expected that increased knowledge of Lepidopteran gut immunity may be utilized for pest biological control in the future. PMID:26872544

  11. Gut Microbiota and Celiac Disease.

    PubMed

    Marasco, Giovanni; Di Biase, Anna Rita; Schiumerini, Ramona; Eusebi, Leonardo Henry; Iughetti, Lorenzo; Ravaioli, Federico; Scaioli, Eleonora; Colecchia, Antonio; Festi, Davide

    2016-06-01

    Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gut microbiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gut microbiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gut microbiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gut microbiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting. PMID:26725064

  12. Bacterial Metabolite Indole Modulates Incretin Secretion from Intestinal Enteroendocrine L Cells

    PubMed Central

    Chimerel, Catalin; Emery, Edward; Summers, David K.; Keyser, Ulrich; Gribble, Fiona M.; Reimann, Frank

    2014-01-01

    Summary It has long been speculated that metabolites, produced by gut microbiota, influence host metabolism in health and diseases. Here, we reveal that indole, a metabolite produced from the dissimilation of tryptophan, is able to modulate the secretion of glucagon-like peptide-1 (GLP-1) from immortalized and primary mouse colonic L cells. Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods. These effects were attributed to the ability of indole to affect two key molecular mechanisms in L cells. On the one hand, indole inhibited voltage-gated K+ channels, increased the temporal width of action potentials fired by L cells, and led to enhanced Ca2+ entry, thereby acutely stimulating GLP-1 secretion. On the other hand, indole slowed ATP production by blocking NADH dehydrogenase, thus leading to a prolonged reduction of GLP-1 secretion. Our results identify indole as a signaling molecule by which gut microbiota communicate with L cells and influence host metabolism. PMID:25456122

  13. Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

    PubMed Central

    Meleine, Mathieu; Matricon, Julien

    2014-01-01

    According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical

  14. Gender-related differences in irritable bowel syndrome: potential mechanisms of sex hormones.

    PubMed

    Meleine, Mathieu; Matricon, Julien

    2014-06-14

    According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical

  15. Developmental origins of a novel gut morphology in frogs.

    PubMed

    Bloom, Stephanie; Ledon-Rettig, Cris; Infante, Carlos; Everly, Anne; Hanken, James; Nascone-Yoder, Nanette

    2013-05-01

    Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation. PMID:23607305

  16. The Gut Microbiome and Obesity.

    PubMed

    John, George Kunnackal; Mullin, Gerard E

    2016-07-01

    The gut microbiome consists of trillions of bacteria which play an important role in human metabolism. Animal and human studies have implicated distortion of the normal microbial balance in obesity and metabolic syndrome. Bacteria causing weight gain are thought to induce the expression of genes related to lipid and carbohydrate metabolism thereby leading to greater energy harvest from the diet. There is a large body of evidence demonstrating that alteration in the proportion of Bacteroidetes and Firmicutes leads to the development of obesity, but this has been recently challenged. It is likely that the influence of gut microbiome on obesity is much more complex than simply an imbalance in the proportion of these phyla of bacteria. Modulation of the gut microbiome through diet, pre- and probiotics, antibiotics, surgery, and fecal transplantation has the potential to majorly impact the obesity epidemic. PMID:27255389

  17. Natural GUT and the cosmology

    NASA Astrophysics Data System (ADS)

    Maekawa, Nobuhiro

    2012-07-01

    In the natural GUT, not only realistic quark and lepton mass matrices can be obtained but also the most serious problem in the SUSY GUT, which is called the doublet-triplet splitting problem, can be solved under the natural assumption that all the interactions which are allowed by the symmetry are introduced with O(1) coefficients (including the higher dimensional operators). In this manuscript, we examine several cosmological aspects which are related with the natural GUT, B - L-genesis, non-thermal production of dark matter (DM), vacuum selection by particle production, and the inflation after the trapping. These works are based on several papers[1, 2, 3] collaborated with S. Enomoto, S. Iida, Y. Kurata, and T. Matsuda.

  18. Natural GUT and the cosmology

    SciTech Connect

    Maekawa, Nobuhiro

    2012-07-27

    In the natural GUT, not only realistic quark and lepton mass matrices can be obtained but also the most serious problem in the SUSY GUT, which is called the doublet-triplet splitting problem, can be solved under the natural assumption that all the interactions which are allowed by the symmetry are introduced with O(1) coefficients (including the higher dimensional operators). In this manuscript, we examine several cosmological aspects which are related with the natural GUT, B - L-genesis, non-thermal production of dark matter (DM), vacuum selection by particle production, and the inflation after the trapping. These works are based on several papers[1, 2, 3] collaborated with S. Enomoto, S. Iida, Y. Kurata, and T. Matsuda.

  19. Global F-theory GUTs

    SciTech Connect

    Blumenhagen, Ralph; Grimm, Thomas W.; Jurke, Benjamin; Weigand, Timo; /SLAC

    2010-08-26

    We construct global F-theory GUT models on del Pezzo surfaces in compact Calabi-Yau fourfolds realized as complete intersections of two hypersurface constraints. The intersections of the GUT brane and the flavour branes as well as the gauge flux are described by the spectral cover construction. We consider a split S[U(4) x U(1){sub X}] spectral cover, which allows for the phenomenologically relevant Yukawa couplings and GUT breaking to the MSSM via hypercharge flux while preventing dimension-4 proton decay. General expressions for the massless spectrum, consistency conditions and a new method for the computation of curvature-induced tadpoles are presented. We also provide a geometric toolkit for further model searches in the framework of toric geometry. Finally, an explicit global model with three chiral generations and all required Yukawa couplings is defined on a Calabi-Yau fourfold which is fibered over the del Pezzo transition of the Fano threefold P{sup 4}.

  20. Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation

    PubMed Central

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaoyuan D; Gray, Clint; Vickers, Mark H

    2015-01-01

    Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1β and TNFα concentrations. Gut Tas1R1, IL-1β, TNFα, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut. PMID:26493953

  1. Sex, Body Mass Index, and Dietary Fiber Intake Influence the Human Gut Microbiome

    PubMed Central

    Dominianni, Christine; Sinha, Rashmi; Goedert, James J.; Pei, Zhiheng; Yang, Liying; Hayes, Richard B.; Ahn, Jiyoung

    2015-01-01

    Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m2 vs. <25 kg/m2) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention. PMID:25874569

  2. Preoperative Use of Incretins Is Associated With Increased Diabetes Remission After RYGB Surgery Among Patients Taking Insulin

    PubMed Central

    Wood, G Craig; Gerhard, Glenn S.; Benotti, Peter; Petrick, Anthony T.; Gabrielsen, Jon D.; Strodel, William E.; Ibele, Anna; Rolston, David D.; Still, Christopher D.; Argyropoulos, George

    2016-01-01

    Objective The main goal of this study was to determine the effects of incretins on type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery for patients taking insulin. Background Type 2 diabetes is a chronic disease with potentially debilitating consequences. RYGB surgery is one of the few interventions that can remit T2D. Preoperative use of insulin, however, predisposes to significantly lower T2D remission rates. Methods A retrospective cohort of 690 T2D patients with at least 12 months follow-up and available electronic medical records was used to identify 37 T2D patients who were actively using a Glucagon-like peptide 1 (GLP-1) agonist in addition to another antidiabetic medication, during the preoperative period. Results Here, we report that use of insulin, along with other antidiabetic medications, significantly diminished overall T2D remission rates 14 months after RYGB surgery (9%) compared with patients not taking insulin (56%). Addition of the GLP-1 agonist, however, increased significantly T2D early remission rates (22%), compared with patients not taking the GLP-1 agonist (4%). Moreover, the 6-year remission rates were also significantly higher for the former group of patients. The GLP-1 agonist did not improve the remission rates of diabetic patients not taking insulin as part of their pharmacotherapy. Conclusions Preoperative use of antidiabetic medication, coupled with an incretin agonist, could significantly improve the odds of T2D remission after RYGB surgery in patients also using insulin. PMID:24646545

  3. Dynamic phages in the swine gut ecosystem

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phages are important drivers of ecosystem functions, yet they are often overlooked in gut microbiome studies. Inclusion of phages in gut microbiome analyses is essential to deciphering complex gut ecology under both normal and disturbed conditions. To assess the effect of antibiotics on phage activi...

  4. The gut microbiota, obesity and insulin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflam...

  5. Glucagon-like peptide 2 therapy reduces the negative impacts the proinflammatory response in the gut of calves with coccidiosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Damage to the intestinal epithelium reduces nutrient absorption and animal growth, and can have negative long-term health effects on livestock. The intestinotropic hormone glucagon-like peptide 2 (GLP-2) contributes to gut integrity, reduces inflammation, and improves nutrient absorption. The presen...

  6. [Hormonal dysnatremia].

    PubMed

    Karaca, P; Desailloud, R

    2013-10-01

    Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS. PMID:24356291

  7. The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions

    PubMed Central

    Mastrogiannaki, Maria; Matak, Pavle

    2013-01-01

    Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2–based therapeutic strategies in iron-related pathological conditions. PMID:23678007

  8. The environment within: how gut microbiota may influence metabolism and body composition

    PubMed Central

    Vrieze, A.; Holleman, F.; Zoetendal, E. G.; de Vos, W. M.; Hoekstra, J. B. L.

    2010-01-01

    Obesity, diabetes and consequently atherosclerotic vascular disease have become major health and public health issues worldwide. The increasing and staggering prevalence of obesity might not only be explained by nutritional habits or the reduction of energy expenditure through decreased physical activity. In addition, recent studies have focused on intestinal microbiota as environmental factors that increase energy yield from diet, regulate peripheral metabolism and thereby increase body weight. Obesity is associated with substantial changes in composition and metabolic function of gut microbiota, but the pathophysiological processes driving this bidirectional relationship have not been fully elucidated. This review discusses the relationships between the following: composition of gut microbiota, energy extracted from diet, synthesis of gut hormones involved in energy homeostasis, production of butyrate and the regulation of fat storage. PMID:20101384

  9. Gut indigenous microbiota and epigenetics

    PubMed Central

    Shenderov, Boris Arkadievich

    2012-01-01

    This review introduces and discusses data regarding fundamental and applied investigations in mammalian epigenomics and gut microbiota received over the last 10 years. Analysis of these data enabled us first to come to the conclusion that the multiple low-molecular-weight substances of indigenous gut microbiota origin should be considered one of the main endogenous factors actively participating in epigenomic mechanisms that are responsible for the mammalian genome reprograming and post-translated modifications. Gut microecological imbalance caused by various biogenic and abiogenic agents and factors can produce different epigenetic abnormalities and the onset and progression of metabolic diseases associated. The authors substantiate the necessity to create an international project ‘Human Gut Microbiota and Epigenomics’ that facilitates interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics, and metabolomics investigations as well as in disease prevention and treatment. Some priority scientific and applied directions in the current omic technologies coupled with gnotobiological approaches are suggested that can open a new era in characterizing the role of the symbiotic microbiota small metabolic and signal molecules in the host epigenomics. Although the discussed subject is only at an early stage its validation can open novel approaches in drug discovery studies. PMID:23990811

  10. [Current view on gut microbiota].

    PubMed

    Bourlioux, P

    2014-01-01

    Gut microbiota is more and more important since metagenomic research have brought new knowledge on this topic especially for human health. Firstly, gut microbiota is a key element for our organism he lives in symbiosis with. Secondly, it interacts favorably with many physiological functions of our organism. Thirdly, at the opposite, it can be an active participant in intestinal pathologies linked to a dysbiosis mainly in chronic inflammatory bowel diseases like Crohn disease or ulcerative colitis but also in obesity, metabolic syndrome, and more prudently in autism and behavioral disorders. In order to keep a good health, it is essential to protect our gut microbiota as soon as our young age and maintain it healthy. Face to a more and more important number of publications for treating certain digestive diseases with fecal microbial transplantation, it needs to be very careful and recommend further studies in order to assess risks and define standardized protocols. Gut microbiota metabolic capacities towards xenobiotics need to be developed, and we must take an interest in the modifications they induce on medicinal molecules. On the other hand, it is essential to study the potent effects of pesticides and other pollutants on microbiota functions. PMID:24438664

  11. Gut microbiota and related diseases: clinical features.

    PubMed

    Stanghellini, Vincenzo; Barbara, Giovanni; Cremon, Cesare; Cogliandro, Rosanna; Antonucci, Alexandra; Gabusi, Veronica; Frisoni, Chiara; De Giorgio, Roberto; Grasso, Valentina; Serra, Mauro; Corinaldesi, Roberto

    2010-10-01

    Intestinal microbiota is essential for gut homeostasis. Specifically, the microorganisms inhabiting the gut lumen interact with the intestinal immune system, supply key nutrients for the major components of the gut wall, and modulate energy metabolism. Host-microbiome interactions can be either beneficial or deleterious, driving gastrointestinal lymphoid tissue activities and shaping gut wall structures. This overview briefly focuses on the potential role played by abnormalities in gut microbiota and relative responses of the gastrointestinal tract in the determination of important pathological conditions such as the irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. PMID:20865476

  12. Novel Gut-Based Pharmacology of Metformin in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Napolitano, Antonella; Miller, Sam; Nicholls, Andrew W.; Baker, David; Van Horn, Stephanie; Thomas, Elizabeth; Rajpal, Deepak; Spivak, Aaron; Brown, James R.; Nunez, Derek J.

    2014-01-01

    Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK) activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology. We hypothesized that the pharmacology of metformin includes alteration of bile acid recirculation and gut microbiota resulting in enhanced enteroendocrine hormone secretion. In this study we evaluated T2DM subjects on and off metformin monotherapy to characterize the gut-based mechanisms of metformin. Subjects were studied at 4 time points: (i) at baseline on metformin, (ii) 7 days after stopping metformin, (iii) when fasting blood glucose (FBG) had risen by 25% after stopping metformin, and (iv) when FBG returned to baseline levels after restarting the metformin. At these timepoints we profiled glucose, insulin, gut hormones (glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose-dependent insulinotropic peptide (GIP) and bile acids in blood, as well as duodenal and faecal bile acids and gut microbiota. We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates. These effects reversed when metformin was restarted. Effects on circulating PYY were more modest, while GIP changes were negligible. Microbiota abundance of the phylum Firmicutes was positively correlated with changes in cholic acid and conjugates, while Bacteroidetes abundance was negatively correlated. Firmicutes and Bacteroidetes representation were also correlated with levels of serum PYY. Our study suggests that metformin

  13. Sex hormones in the modulation of irritable bowel syndrome.

    PubMed

    Mulak, Agata; Taché, Yvette; Larauche, Muriel

    2014-03-14

    Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of "microgenderome" related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder. PMID:24627581

  14. Incretins: Clinical Perspectives, Relevance, and Applications for the Primary Care Physician in the Treatment of Patients With Type 2 Diabetes Mellitus

    PubMed Central

    Unger, Jeff

    2010-01-01

    The prevalence of type 2 diabetes mellitus (DM) is increasing substantially in the United States. Almost 24 million people have the disease, with most of these patients treated by primary care physicians. Optimal treatment of type 2 DM requires physicians to understand the pathophysiology of this disorder. Once the physiologic defects are determined, lifestyle interventions and glucoselowering medications can be prescribed to minimize the state of chronic hyperglycemia and to address the pathophysiologic defects associated with type 2 DM. Other metabolic abnormalities, including hyperlipidemia, hypertension, and oxidative stress, must also be addressed to reduce the patient's risk of cardiovascular disease. The incretin system plays a role in the pathogenesis of type 2 DM. Incretin-based therapies, including glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors, have shown efficacy and safety in treating type 2 DM and have been reviewed in consensus treatment algorithms. This article provides an overview of the role of incretin-based therapies in the management of patients with type 2 DM and how primary care physicians can incorporate these agents into their practice. PMID:21106866

  15. Gut microbiome, gut function, and probiotics: Implications for health.

    PubMed

    Hajela, Neerja; Ramakrishna, B S; Nair, G Balakrish; Abraham, Philip; Gopalan, Sarath; Ganguly, Nirmal K

    2015-03-01

    New insights from a rapidly developing field of research have ushered in a new era of understanding of the complexity of host-microbe interactions within the human body. The paradigm shift from culturing to metagenomics has provided an insight into the complex diversity of the microbial species that we harbor, revealing the fact that we are in fact more microbes than human cells. The largest consortium of these microbes resides in the gut and is called the gut microbiota. This new science has expanded the ability to document shifts in microbial populations to an unparalleled degree. It is now understood that signals from the microbiota provide trophic, nutritional, metabolic, and protective effects for the development and maintenance of the host digestive, immune, and neuroendocrine system. Evidence linking changes in the gut microbiota to gastrointestinal and extraintestinal disorders like irritable bowel syndrome, inflammatory bowel disease, obesity, diabetes, and celiac disease have begun to emerge recently. Probiotics act through diverse mechanisms positively affecting the composition and/or function of the commensal microbiota and alter host immunological responses. Well-controlled intervention trials, systematic reviews, and meta-analysis provide convincing evidence for the benefit of probiotics in prevention and treatment of gastrointestinal as well as extraintestinal disorders. PMID:25917520

  16. Prebiotic inulin: Useful dietary adjuncts to manipulate the livestock gut microflora

    PubMed Central

    Samanta, A.K.; Jayapal, Natasha; Senani, S.; Kolte, A.P.; Sridhar, Manpal

    2013-01-01

    In recent years, there has been a growing appreciation on the relevance of gastrointestinal microflora in both ruminants and non-ruminants owing to revelation of their role in several physiological functions including digestion, nutrient utilization, pathogen exclusion, gastrointestinal development, immunity system, gut gene expression and quality of animal products. The ban imposed on the use of antibiotics and hormones in feed has compelled animal researchers in finding an alternative which could overcome the issues of conventional feed additives. Though the concept of prebiotic was evolved keeping in mind the gastrointestinal flora of human beings, presently animal researchers are exploring the efficiency of prebiotic (inulin) for modulating the gut ecosystem of both ruminants and non-ruminants. It was revealed that prebiotic inulin is found to exhibit desirable changes in the gut of non-ruminants like poultry, swine, rabbit etc for augmenting gut health and improvement of product quality. Similarly, in ruminants the prebiotic reduces rumen ammonia nitrogen, methane production, increase microbial protein synthesis and live weight gains in calves. Unlike other feed additives, prebiotic exhibits its effect in multipronged ways for overall increase in the performances of the animals. In coming days, it is expected that prebiotics could be the part of diets in both ruminants and non-ruminants for enabling modulation of gut microflora vis a vis animals productivity in ecological ways. PMID:24159277

  17. GUT implications from neutrino mass

    SciTech Connect

    Carl H. Albright

    2001-06-26

    An overview is given of the experimental neutrino mixing results and types of neutrino models proposed, with special attention to the general features of various GUT models involving intra-family symmetries and horizontal flavor symmetries. Many of the features are then illustrated by a specific SO (10) SUSY GUT model formulated by S.M. Barr and the author which can explain all four types of solar neutrino mixing solutions by various choices of the right-handed Majorana mass matrix. The quantitative nature of the model's large mixing angle solution is used to compare the reaches of a neutrino super beam and a neutrino factory for determining the small U{sub e3} mixing matrix element.

  18. Arabinoxylans, gut microbiota and immunity.

    PubMed

    Mendis, Mihiri; Leclerc, Estelle; Simsek, Senay

    2016-03-30

    Arabinoxylan (AX) is a non-starch polysaccharide found in many cereal grains and is considered as a dietary fiber. Despite their general structure, there is structural heterogeneity among AX originating from different botanical sources. Furthermore, the extraction procedure and hydrolysis by xylolytic enzymes can further render differences to theses AX. The aim of this review was to address the effects of AX on the gut bacteria and their immunomodulatory properties. Given the complex structure of AX, we also aimed to discuss how the structural heterogeneity of AX affects its role in bacterial growth and immunomodulation. The existing literature indicates the role of fine structural details of AX on its potential as polysaccharides that can impact the gut associated microbial growth and immune system. PMID:26794959

  19. Hormones and Obesity

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Women's Health Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  20. Growth hormone deficiency - children

    MedlinePlus

    ... the same age. The child will have normal intelligence in most cases. In older children, puberty may ... hormones cause the body to make. Tests can measure these growth factors. Accurate growth hormone deficiency testing ...

  1. Hormones and Hypertension

    MedlinePlus

    Fact Sheet Hormones and Hypertension What is hypertension? Hypertension, or chronic (long-term) high blood pressure, is a main cause of ... tobacco, alcohol, and certain medications play a part. Hormones made in the kidneys and in blood vessels ...

  2. ADH (Antidiuretic Hormone) Test

    MedlinePlus

    ... Also known as: Vasopressin; AVP Formal name: Antidiuretic Hormone; Arginine Vasopressin Related tests: Osmolality , BUN , Creatinine , Sodium , ... should know? How is it used? The antidiuretic hormone (ADH) test is used to help detect, diagnose, ...

  3. Menopause and Hormones

    MedlinePlus

    ... Consumer Information by Audience For Women Menopause and Hormones: Common Questions Share Tweet Linkedin Pin it More ... reproduction and distribution. Learn More about Menopause and Hormones Menopause--Medicines to Help You Links to other ...

  4. Hormonal effects in newborns

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb babies ...

  5. Cospeciation of gut microbiota with hominids.

    PubMed

    Moeller, Andrew H; Caro-Quintero, Alejandro; Mjungu, Deus; Georgiev, Alexander V; Lonsdorf, Elizabeth V; Muller, Martin N; Pusey, Anne E; Peeters, Martine; Hahn, Beatrice H; Ochman, Howard

    2016-07-22

    The evolutionary origins of the bacterial lineages that populate the human gut are unknown. Here we show that multiple lineages of the predominant bacterial taxa in the gut arose via cospeciation with humans, chimpanzees, bonobos, and gorillas over the past 15 million years. Analyses of strain-level bacterial diversity within hominid gut microbiomes revealed that clades of Bacteroidaceae and Bifidobacteriaceae have been maintained exclusively within host lineages across hundreds of thousands of host generations. Divergence times of these cospeciating gut bacteria are congruent with those of hominids, indicating that nuclear, mitochondrial, and gut bacterial genomes diversified in concert during hominid evolution. This study identifies human gut bacteria descended from ancient symbionts that speciated simultaneously with humans and the African apes. PMID:27463672

  6. Novel hormone "receptors".

    PubMed

    Nemere, Ilka; Hintze, Korry

    2008-02-01

    Our concepts of hormone receptors have, until recently, been narrowly defined. In the last few years, an increasing number of reports identify novel proteins, such as enzymes, acting as receptors. In this review we cover the novel receptors for the hormones atrial naturetic hormone, enterostatin, hepcidin, thyroid hormones, estradiol, progesterone, and the vitamin D metabolites 1,25(OH)(2)D(3) and 24,25(OH)(2)D(3). PMID:17546587

  7. The GOCE User Toolbox (GUT) and Tutorial

    NASA Astrophysics Data System (ADS)

    Bingham, R. J.; Benveniste, J.; Knudsen, P.

    2015-12-01

    The GOCE User Toolbox (GUT) is an integrated suite of tools for the analysis and use of GOCE Level 2 gravity products. GUT supports applications in geodesy, oceanography and solid earth physics. The accompanying GUT tutorial provides information and guidance on how to use the toolbox for a variety of applications within each of these domains. An important motivation for the development of GUT has been the desire that users should be able to exploit the GOCE gravity products to calculate derived products relevant to their particular domains without necessarily needing to understand the technicalities of particular geodetic concepts and algorithms. As such, GUT is also suitable for use as an aid to the teaching of geophysics. A comprehensive and up-to-date set of a-priori data and models are supplied with the toolbox, together with a range of pre-defined workflows, allowing the user to immediately calculate useful geophysical quantities. The toolbox is supported by The GUT Algorithm Description and User Guide and The GUT Install Guide. GUT is cross-platform and may be used on Windows PCs, UNIX/Linux workstations and Macs. GUT version 2.2 was released in April 2014 and, besides some bug-fixes, the capability to calculate the simple Bouguer anomaly was added. Recently, GUT version 3 has been released. Through a collaborative effort between the relevant scientific communities, this version has built on earlier releases by further extending the functionality of the toolbox within the fields of geodesy, oceanography and solid earth physics. Additions include the ability to work directly with gravity gradients, anisotropic diffusive filtering, and the computation of Bouguer and isostatic gravity anomalies. The interface between the user and the toolbox has also been greatly improved and GUT version 3 now includes an attractive and intuitive Graphical User Interface. An associated GUT VCM tool for analysing the GOCE variance covariance matrices is also available.

  8. Aging changes in hormone production

    MedlinePlus

    The endocrine system is made up of organs and tissues that produce hormones. Hormones are natural chemicals produced in one ... hormones that control the other structures in the endocrine system. The amount of these regulating hormones stays about ...

  9. Role of the normal gut microbiota

    PubMed Central

    Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Reddy, D Nageshwar

    2015-01-01

    Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual’s life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool. PMID:26269668

  10. Role of the normal gut microbiota.

    PubMed

    Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Nageshwar Reddy, D

    2015-08-01

    Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool. PMID:26269668

  11. Gut Microbiota of Nonalcoholic Fatty Liver Disease.

    PubMed

    Abdou, Reham M; Zhu, Lixin; Baker, Robert D; Baker, Susan S

    2016-05-01

    The prevalence of nonalcoholic fatty liver disease has been rapidly increasing worldwide. It has become a leading cause of liver transplantation. Accumulating evidence suggests a significant role for gut microbiota in its development and progression. Here we review the effect of gut microbiota on developing hepatic fatty infiltration and its progression. Current literature supports a possible role for gut microbiota in the development of liver steatosis, inflammation and fibrosis. We also review the literature on possible interventions for NAFLD that target the gut microbiota. PMID:26898658

  12. Gut inflammation and microbiome in spondyloarthritis.

    PubMed

    Kabeerdoss, Jayakanthan; Sandhya, Pulukool; Danda, Debashish

    2016-04-01

    Spondyloarthritis (SpA) is chronic inflammatory disease involving joints and the spine. Bowel inflammation is common in SpA, which may be classified as acute or chronic. Chronic gut inflammation is most common in SpA patients with axial involvement as compared to those presenting with peripheral involvement alone. The pathogenesis of gut inflammation in SpA could be explained by two factors-over-activation of immunological cells and altered gut microbiome. This is exemplified by SpA animal models, namely HLA-B27-expressing transgenic animals and SKG mice models. Immunological mechanisms include homing of activated T cells from gut into synovium, excess pro-inflammatory cytokines secretion by immune cells such as IL-23 and genetic variations in immunological genes. The evidence for role of gut microbiome in SpA is gradually emerging. Recently, metagenomic study of gut microbiome by sequencing of microbial nucleic acids has enabled identification of new microbial taxa and their functions in gut of patients with SpA. In SpA, the gut microbiome could emerge as diagnostic and prognostic marker of disease. Modulation of gut microbiome is slated to have therapeutic potential as well. PMID:26719306

  13. Gut Microbiota and Type 1 Diabetes

    PubMed Central

    Vaarala, Outi

    2012-01-01

    The gut immune system has a key role in the development of autoimmune diabetes, and factors that control the gut immune system are also regulators of beta-cell autoimmunity. Gut microbiota modulate the function of the gut immune system by their effect on the innate immune system, such as the intestinal epithelial cells and dendritic cells, and on the adaptive immune system, in particular intestinal T cells. Due to the immunological link between gut and pancreas, e.g. the shared lymphocyte homing receptors, the immunological changes in the gut are reflected in the pancreas. According to animal studies, changes in gut microbiota alter the development of autoimmune diabetes. This has been demonstrated by antibiotics that induce changes in the gut microbiota. Furthermore, gut-colonizing microbes may modify the incidence of autoimmune diabetes in animal models. Deficient toll-like receptor (TLR) signaling, mediating microbial stimulus in immune cells, prevents autoimmune diabetes, which appears to be dependent on alterations in the intestinal microbiota. Although few studies have been conducted in humans, recent studies suggest that the abundance of Bacteroides and lack of butyrate-producing bacteria in fecal microbiota are associated with beta-cell autoimmunity and type 1 diabetes. It is possible that altered gut microbiota are associated with immunological aberrancies in type 1 diabetes. The changes in gut microbiota could lead to alterations in the gut immune system, such as increased gut permeability, small intestinal inflammation, and impaired tolerance to food antigens, all of which are observed in type 1 diabetes. Poor fitness of gut microbiota could explain why children who develop type 1 diabetes are prone to enterovirus infections, and do not develop tolerance to cow milk antigens. These candidate risk factors of type 1 diabetes may imply an increased risk of type 1 diabetes due to the presence of gut microbiota that do not support health. Despite the complex

  14. Was sind hormone?

    NASA Astrophysics Data System (ADS)

    Karlson, P.

    1982-01-01

    Historically, the meaning of the term hormone has changed during the last decades. Morphological studies of secreting cells lead Feyrter to the concept of paracrine action of some hormones. While endocrine regulators are blood-borne, paracrine messengers reach their target cells through the diffusion in the intracellular space. Though it is rather difficult to draw a line between true hormones and hormone-like substances, valid definitions for endocrine and paracrine regulatory systems can be given. The term ‘hormonal control’ should be restricted to endocrine systems. For effectors acting by paracrine mechanisms, the term paramone is proposed in this article.

  15. Hormonal therapies in acne.

    PubMed

    Shaw, James C

    2002-07-01

    Hormones, in particular androgen hormones, are the main cause of acne in men, women, children and adults, in both normal states and endocrine disorders. Therefore, the use of hormonal therapies in acne is rational in concept and gratifying in practice. Although non-hormonal therapies enjoy wide usage and continue to be developed, there is a solid place for hormonal approaches in women with acne, especially adult women with persistent acne. This review covers the physiological basis for hormonal influence in acne, the treatments that are in use today and those that show promise for the future. The main treatments to be discussed are oral contraceptives androgen receptor blockers like spironolactone and flutamide, inhibitors of the enzyme 5 alpha-reductase and topical hormonal treatments. PMID:12083987

  16. High-fat diet alters gut microbiota physiology in mice.

    PubMed

    Daniel, Hannelore; Moghaddas Gholami, Amin; Berry, David; Desmarchelier, Charles; Hahne, Hannes; Loh, Gunnar; Mondot, Stanislas; Lepage, Patricia; Rothballer, Michael; Walker, Alesia; Böhm, Christoph; Wenning, Mareike; Wagner, Michael; Blaut, Michael; Schmitt-Kopplin, Philippe; Kuster, Bernhard; Haller, Dirk; Clavel, Thomas

    2014-02-01

    The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level. PMID:24030595

  17. High-fat diet alters gut microbiota physiology in mice

    PubMed Central

    Daniel, Hannelore; Gholami, Amin Moghaddas; Berry, David; Desmarchelier, Charles; Hahne, Hannes; Loh, Gunnar; Mondot, Stanislas; Lepage, Patricia; Rothballer, Michael; Walker, Alesia; Böhm, Christoph; Wenning, Mareike; Wagner, Michael; Blaut, Michael; Schmitt-Kopplin, Philippe; Kuster, Bernhard; Haller, Dirk; Clavel, Thomas

    2014-01-01

    The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level. PMID:24030595

  18. Endocrine regulation of gut maturation in early life in pigs.

    PubMed

    Thymann, T

    2016-07-01

    After birth, the newborn must adapt to the acute challenges of circulatory changes, active respiration, thermoregulation, microbial colonization, and enteral nutrition. Whereas these processes normally occur without clinical complications in neonates born at term, birth at a preterm state of gestation is associated with high morbidity and mortality. In commercial pig production, perinatal mortality is higher than in any other mammalian species. Asphyxia, hypothermia, hypoglycemia, sepsis, and gut dysmotility, represent some of the most common findings. The intestine is a particularly sensitive organ after birth, as it must adapt acutely to enteral nutrition and microbial colonization. Likewise, during the weaning phase, the intestine must adapt to new diet types. Both critical phases are associated with high morbidity. This review focuses on the endocrine changes occurring around birth and weaning. There are a number of endocrine adaptations in late gestation and early postnatal life that are under influence of development stage and environmental factors such as diet. The review discusses general endocrine changes in perinatal life but specifically focuses on the role of glucagon-like peptide-2. This gut-derived hormone plays a key role in development and function of the intestine in early life. PMID:27345327

  19. Incretin-like effects of small molecule trace amine-associated receptor 1 agonists

    PubMed Central

    Raab, Susanne; Wang, Haiyan; Uhles, Sabine; Cole, Nadine; Alvarez-Sanchez, Ruben; Künnecke, Basil; Ullmer, Christoph; Matile, Hugues; Bedoucha, Marc; Norcross, Roger D.; Ottaway-Parker, Nickki; Perez-Tilve, Diego; Conde Knape, Karin; Tschöp, Matthias H.; Hoener, Marius C.; Sewing, Sabine

    2015-01-01

    Objective Type 2 diabetes and obesity are emerging pandemics in the 21st century creating worldwide urgency for the development of novel and safe therapies. We investigated trace amine-associated receptor 1 (TAAR1) as a novel target contributing to the control of glucose homeostasis and body weight. Methods We investigated the peripheral human tissue distribution of TAAR1 by immunohistochemistry and tested the effect of a small molecule TAAR1 agonist on insulin secretion in vitro using INS1E cells and human islets and on glucose tolerance in C57Bl6, and db/db mice. Body weight effects were investigated in obese DIO mice. Results TAAR1 activation by a selective small molecule agonist increased glucose-dependent insulin secretion in INS1E cells and human islets and elevated plasma PYY and GLP-1 levels in mice. In diabetic db/db mice, the TAAR1 agonist normalized glucose excursion during an oral glucose tolerance test. Sub-chronic treatment of diet-induced obese (DIO) mice with the TAAR1 agonist resulted in reduced food intake and body weight. Furthermore insulin sensitivity was improved and plasma triglyceride levels and liver triglyceride content were lower than in controls. Conclusions We have identified TAAR1 as a novel integrator of metabolic control, which acts on gastrointestinal and pancreatic islet hormone secretion. Thus TAAR1 qualifies as a novel and promising target for the treatment of type 2 diabetes and obesity. PMID:26844206

  20. Altered gut transcriptome in spondyloarthropathy

    PubMed Central

    Laukens, D; Peeters, H; Cruyssen, B V; Boonefaes, T; Elewaut, D; De Keyser, F; Mielants, H; Cuvelier, C; Veys, E M; Knecht, K; Van Hummelen, P; Remaut, E; Steidler, L; De Vos, M; Rottiers, P

    2006-01-01

    Background Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn's disease. Inflammation is manifested clinically in Crohn's disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn's disease. Aims To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn's disease and to examine global gene expression in non‐inflamed colon biopsy specimens and screen patients for differentially expressed genes. Methods Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn's disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn's disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass‐based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn's disease and 10 controls. Results 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn's disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn's disease. Conclusion The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn's disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn's disease in patients with SpA can be considered. PMID:16476712

  1. Clostridial disease of the gut.

    PubMed

    Borriello, S P

    1995-06-01

    Clostridia are an important cause of morbidity and mortality in humans and animals. Some of the most common clostridial infections are those of the gut. The primary infections in humans are Clostridium perfringens food poisoning and Clostridium difficile-mediated antibiotic-associated diarrhea and colitis. Less common but important infections include non-food poisoning C. perfringens nosocomial diarrhea and C. perfringens type C necrotizing jejunitis (pig-bel). C. perfringens is also the dominant cause of gastrointestinal infections in animals, although Clostridium septicum causing braxy in sheep, Clostridium colinum causing ulcerative enteritis is avian species, and Clostridium spiroforme causing enterotoxemia in rabbits are important exceptions. PMID:7548565

  2. Differences in beta-cell function and insulin secretion in Black vs. White obese adolescents: Do incretin hormones play a role?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Black youth are at higher risk for type 2 diabetes (T2D) than their White peers. Previously we demonstrated that for the same degree of insulin sensitivity, Black youth have an upregulated beta-cell function and insulin hypersecretion, in response to intravenous (IV) glucose, compared with Whites. T...

  3. Whey proteins have beneficial effects on intestinal enteroendocrine cells stimulating cell growth and increasing the production and secretion of incretin hormones.

    PubMed

    Gillespie, Anna L; Calderwood, Danielle; Hobson, Laura; Green, Brian D

    2015-12-15

    Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin). ALA is a highly potent GLP-1 secretagogue which also increases the intracellular levels of GLP-1. Conversely, whey proteins and hydrolysates had little impact on GIP secretion. This appears to be the first investigation of the effects of the three major proteins of YW and CW on EE cells. The anti-diabetic potential of whey proteins should be further investigated. PMID:26190610

  4. GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION

    PubMed Central

    Yang, Tao; Santisteban, Monica M.; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J.; Raizada, Mohan K.; Mohamadzadeh, Mansour

    2015-01-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. The present study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension since genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of two rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes to Bacteroidetes ratio. These changes were accompanied with decreases in acetate- and butyrate-producing bacteria. Additionally, the microbiota of a small cohort of human hypertension patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes to Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes to Bacteroidetes ratio. These observations demonstrate that high BP is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  5. Gut dysbiosis is linked to hypertension.

    PubMed

    Yang, Tao; Santisteban, Monica M; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J; Raizada, Mohan K; Mohamadzadeh, Mansour

    2015-06-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  6. [Gut microbiota: Description, role and pathophysiologic implications].

    PubMed

    Landman, C; Quévrain, E

    2016-06-01

    The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. PMID:26749318

  7. Human growth hormone.

    PubMed

    Strobl, J S; Thomas, M J

    1994-03-01

    The study of human growth hormone is a little more than 100 years old. Growth hormone, first identified for its dramatic effect on longitudinal growth, is now known to exert generalized effects on protein, lipid, and carbohydrate metabolism. Additional roles for growth hormone in human physiology are likely to be discovered in the areas of sleep research and reproduction. Furthermore, there is some indication that growth hormone also may be involved in the regulation of immune function, mental well-being, and the aging process. Recombinant DNA technology has provided an abundant and safe, albeit expensive, supply of human growth hormone for human use, but the pharmacological properties of growth hormone are poor. Most growth hormone-deficient individuals exhibit a secretory defect rather than a primary defect in growth hormone production, however, and advances in our understanding of the neuroendocrine regulation of growth hormone secretion have established the basis for the use of drugs to stimulate release of endogenously synthesized growth hormone. This promises to be an important area for future drug development. PMID:8190748

  8. The gut microbiome: scourge, sentinel or spectator?

    PubMed Central

    Korecka, Agata; Arulampalam, Velmurugesan

    2012-01-01

    The gut microbiota consists of trillions of prokaryotes that reside in the intestinal mucosa. This long-established commensalism indicates that these microbes are an integral part of the eukaryotic host. Recent research findings have implicated the dynamics of microbial function in setting thresholds for many physiological parameters. Conversely, it has been convincingly argued that dysbiosis, representing microbial imbalance, may be an important underlying factor that contributes to a variety of diseases, inside and outside the gut. This review discusses the latest findings, including enterotype classification, changes brought on by dysbiosis, gut inflammation, and metabolic mediators in an attempt to underscore the importance of the gut microbiota for human health. A cautiously optimistic idea is taking hold, invoking the gut microbiota as a medium to track, target and treat a plethora of diseases. PMID:22368769

  9. A catalog of the mouse gut metagenome.

    PubMed

    Xiao, Liang; Feng, Qiang; Liang, Suisha; Sonne, Si Brask; Xia, Zhongkui; Qiu, Xinmin; Li, Xiaoping; Long, Hua; Zhang, Jianfeng; Zhang, Dongya; Liu, Chuan; Fang, Zhiwei; Chou, Joyce; Glanville, Jacob; Hao, Qin; Kotowska, Dorota; Colding, Camilla; Licht, Tine Rask; Wu, Donghai; Yu, Jun; Sung, Joseph Jao Yiu; Liang, Qiaoyi; Li, Junhua; Jia, Huijue; Lan, Zhou; Tremaroli, Valentina; Dworzynski, Piotr; Nielsen, H Bjørn; Bäckhed, Fredrik; Doré, Joël; Le Chatelier, Emmanuelle; Ehrlich, S Dusko; Lin, John C; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2015-10-01

    We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies. PMID:26414350

  10. Antibiotics and the gut microbiota

    PubMed Central

    Modi, Sheetal R.; Collins, James J.; Relman, David A.

    2014-01-01

    Antibiotics have been a cornerstone of innovation in the fields of public health, agriculture, and medicine. However, recent studies have shed new light on the collateral damage they impart on the indigenous host-associated communities. These drugs have been found to alter the taxonomic, genomic, and functional capacity of the human gut microbiota, with effects that are rapid and sometimes persistent. Broad-spectrum antibiotics reduce bacterial diversity while expanding and collapsing membership of specific indigenous taxa. Furthermore, antibiotic treatment selects for resistant bacteria, increases opportunities for horizontal gene transfer, and enables intrusion of pathogenic organisms through depletion of occupied natural niches, with profound implications for the emergence of resistance. Because these pervasive alterations can be viewed as an uncoupling of mutualistic host-microbe relationships, it is valuable to reconsider antimicrobial therapies in the context of an ecological framework. Understanding the biology of competitive exclusion, interspecies protection, and gene flow of adaptive functions in the gut environment may inform the design of new strategies that treat infections while preserving the ecology of our beneficial constituents. PMID:25271726

  11. Interaction between ingested nutrients and gut endocrine cells in patients with irritable bowel syndrome (Review)

    PubMed Central

    EL-SALHY, MAGDY; GILJA, ODD HELGE; GUNDERSEN, DORIS; HATLEBAKK, JAN G.; HAUSKEN, TRYGVE

    2014-01-01

    Several endocrine cell abnormalities have been reported in different segments of the gastrointestinal tract of patients with irritable bowel syndrome (IBS). These cells have specialized microvilli that project into the lumen; they function as sensors for the gut contents and respond to luminal stimuli (mostly ingested nutrients) by releasing hormones into the lamina propria, where they exert their effects via a paracrine/endocrine mode of action. Certain food items trigger the symptoms experienced by IBS patients, including those rich in fermentable oligo-, di- and monosaccharides, and polyols (FODMAPs). In this review, we present the argument that the effects of both FODMAPs and the proportional intake of proteins, fats and carbohydrates on IBS symptoms may be caused by an interaction with the gut endocrine cells. Since the gut hormones control and regulate gastrointestinal motility and sensation, this interaction may be responsible for abnormal gastrointestinal motility and the visceral hypersensitivity observed in these patients. There is no consistent evidence that IBS patients suffer from food allergy. The role of gluten intolerance in the development of IBS symptoms in these patients remains a matter of controversy. Individual guidance on food management, which includes restrictions in the intake of FODMAP-rich foods and testing diets with different proportions of proteins, fats and carbohydrates has been found to reduce the symptoms, improve the quality of life, and make the habitual diet of IBS patients more healthy. PMID:24939595

  12. Involvement of the gut chemosensory system in the regulation of colonic anion secretion.

    PubMed

    Kuwahara, A

    2015-01-01

    The primary function of the gastrointestinal (GI) tract is the extraction of nutrients from the diet. Therefore, the GI tract must possess an efficient surveillance system that continuously monitors the luminal content for beneficial or harmful compounds. Recent studies have shown that specialized cells in the intestinal lining can sense changes in this content. These changes directly influence fundamental GI processes such as secretion, motility, and local blood flow via hormonal and/or neuronal pathways. Until recently, most studies examining the control of ion transport in the colon have focused on neural and hormonal regulation. However, study of the regulation of gut function by the gut chemosensory system has become increasingly important, as failure of this system causes dysfunctions in host homeostasis, as well as functional GI disorders. Furthermore, regulation of ion transport in the colon is critical for host defense and for electrolytes balance. This review discusses the role of the gut chemosensory system in epithelial transport, with a particular emphasis on the colon. PMID:25866781

  13. Involvement of the Gut Chemosensory System in the Regulation of Colonic Anion Secretion

    PubMed Central

    Kuwahara, A.

    2015-01-01

    The primary function of the gastrointestinal (GI) tract is the extraction of nutrients from the diet. Therefore, the GI tract must possess an efficient surveillance system that continuously monitors the luminal content for beneficial or harmful compounds. Recent studies have shown that specialized cells in the intestinal lining can sense changes in this content. These changes directly influence fundamental GI processes such as secretion, motility, and local blood flow via hormonal and/or neuronal pathways. Until recently, most studies examining the control of ion transport in the colon have focused on neural and hormonal regulation. However, study of the regulation of gut function by the gut chemosensory system has become increasingly important, as failure of this system causes dysfunctions in host homeostasis, as well as functional GI disorders. Furthermore, regulation of ion transport in the colon is critical for host defense and for electrolytes balance. This review discusses the role of the gut chemosensory system in epithelial transport, with a particular emphasis on the colon. PMID:25866781

  14. Hormonal therapy for acne.

    PubMed

    George, Rosalyn; Clarke, Shari; Thiboutot, Diane

    2008-09-01

    Acne affects more than 40 million people, of which more than half are women older than 25 years of age. These women frequently fail traditional therapy and have high relapse rates even after isotretinoin. Recent advances in research have helped to delineate the important role hormones play in the pathogenesis of acne. Androgens such as dihydrotestosterone and testosterone, the adrenal precursor dehydroepiandrosterone sulfate, estrogens, growth hormone, and insulin-like growth factors may all contribute to the development of acne. Hormonal therapy remains an important part of the arsenal of acne treatments available to the clinician. Women dealing with acne, even those without increased serum androgens, may benefit from hormonal treatments. The mainstays of hormonal therapy include oral contraceptives and antiandrogens such as spironolactone, cyproterone acetate, or flutamide. In this article, we discuss the effects of hormones on the pathogenesis of acne, evaluation of women with suspected endocrine abnormalities, and the myriad of treatment options available. PMID:18786497

  15. Hormones and endometrial carcinogenesis.

    PubMed

    Kamal, Areege; Tempest, Nicola; Parkes, Christina; Alnafakh, Rafah; Makrydima, Sofia; Adishesh, Meera; Hapangama, Dharani K

    2016-02-01

    Endometrial cancer (EC) is the commonest gynaecological cancer in the Western World with an alarmingly increasing incidence related to longevity and obesity. Ovarian hormones regulate normal human endometrial cell proliferation, regeneration and function therefore are implicated in endometrial carcinogenesis directly or via influencing other hormones and metabolic pathways. Although the role of unopposed oestrogen in the pathogenesis of EC has received considerable attention, the emerging role of other hormones in this process, such as androgens and gonadotropin-releasing hormones (GnRH) is less well recognised. This review aims to consolidate the current knowledge of the involvement of the three main endogenous ovarian hormones (oestrogens, progesterone and androgens) as well as the other hormones in endometrial carcinogenesis, to identify important avenues for future research. PMID:26966933

  16. Exogenous ghrelin regulates proliferation and apoptosis in the hypotrophic gut mucosa of the rat.

    PubMed

    de Segura, Ignacio A Gómez; Vallejo-Cremades, María Teresa; Lomas, Jesús; Sánchez, Miriam F; Caballero, María Isabel; Largo, Carlota; De Miguel, Enrique

    2010-04-01

    Ghrelin is the natural endogenous ligand for growth hormone secretagogue receptors. This peptide regulates energy homeostasis and expenditure and is a potential link between gut absorptive function and growth. We hypothesized that ghrelin may induce a proliferative and antiapoptotic action promoting the recovery of the hypotrophic gut mucosa. Therefore, the aim of the study was to determine the action of exogenous ghrelin following gut mucosal hypotrophia in rats fed an elemental diet. An elemental diet provides readily absorbable simple nutrients and is usually given to patients with absorptive dysfunction. Male Wistar rats (n = 48) were fed the elemental diet for one week to induce mucosal hypotrophy and then treated for another week with systemic ghrelin and pair-fed with either a normoproteic or hyperproteic isocaloric liquid diet. Another group received a standard diet instead of the elemental diet and served as control (normotrophy). The elemental diet induced intestinal hypotrophia characterized by decreased proliferation in the ileum and increased apoptosis in jejunum and ileum. Ghrelin administration restored normal levels of proliferation in the ileum and apoptosis in the jejunum, with partial apoptosis restoration in the ileum. Ghrelin levels in plasma and fundus were increased in all groups, although the highest levels were found in rats treated with exogenous ghrelin. Ghrelin administration has a positive effect in the hypotrophic gut, regulating both proliferation and apoptosis towards a physiological balance counteracting the negative changes induced by an elemental diet in the intestines. PMID:20407078

  17. Prebiotics Modulate the Effects of Antibiotics on Gut Microbial Diversity and Functioning in Vitro

    PubMed Central

    Johnson, Laura P.; Walton, Gemma E.; Psichas, Arianna; Frost, Gary S.; Gibson, Glenn R.; Barraclough, Timothy G.

    2015-01-01

    Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs), which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation—another method used to modulate gut composition and function—could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre), inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria) or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota. PMID:26053617

  18. Prebiotics Modulate the Effects of Antibiotics on Gut Microbial Diversity and Functioning in Vitro.

    PubMed

    Johnson, Laura P; Walton, Gemma E; Psichas, Arianna; Frost, Gary S; Gibson, Glenn R; Barraclough, Timothy G

    2015-06-01

    Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs), which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation--another method used to modulate gut composition and function--could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre), inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria) or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota. PMID:26053617

  19. The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology.

    PubMed

    O'Callaghan, T F; Ross, R P; Stanton, C; Clarke, G

    2016-07-01

    The gut microbiome exerts a marked influence on host physiology, and manipulation of its composition has repeatedly been shown to influence host metabolism and body composition. This virtual endocrine organ also has a role in the regulation of the plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Control over the hypothalamic-pituitary-adrenal axis also appears to be under the influence of the gut microbiota. This is clear from studies in microbiota-deficient germ-free animals with exaggerated responses to psychological stress that can be normalized by monocolonization with certain bacterial species including Bifidobacterium infantis. Therapeutic targeting of the gut microbiota may thus be useful in treating or preventing stress-related microbiome-gut-brain axis disorders and metabolic diseases, much the same way as redirections of metabolopathies can be achieved through more traditional endocrine hormone-based interventions. Moreover, the implications of these findings need to be considered in the context of farm and domestic animal physiology, behavior, and food safety. PMID:27345323

  20. Regional Variation in Use of a New Class of Antidiabetic Medication Among Medicare Beneficiaries: The Case of Incretin Mimetics

    PubMed Central

    Marcum, Zachary A.; Driessen, Julia; Thorpe, Carolyn T.; Donohue, Julie M.; Gellad, Walid F.

    2016-01-01

    Background When incretin mimetic (IM) medications were introduced in 2005, their effectiveness compared other less-expensive second-line diabetes therapies was unknown, especially for older adults. Physicians likely had uncertainty about the role of IMs in the diabetes treatment armamentarium. Regional variation in uptake of IMs may be marker of such uncertainty. Objective To investigate the extent of regional variation in the use of IMs among beneficiaries and estimate the cost implications for Medicare. Methods This was a cross-sectional analysis of 2009–2010 claims from a nationally representative sample of 238 499 Medicare Part D beneficiaries aged ≥65 years, who were continuously enrolled in fee-for-service Medicare and Part D and filled ≥1 antidiabetic prescription. Beneficiaries were assigned to 1 306 hospital-referral regions (HRRs) using ZIP codes. The main outcome was adjusted proportion of antidiabetic users an HRR receiving an IM. Results Overall, 29 933 beneficiaries (12.6%) filled an IM prescription, including 26 939 (11. for sitagliptin or saxagliptin and 3718 (1.6%) for exenatide or liraglutide. The adjusted proportion of beneficiaries using varied more than 3-fold across HRRs, from 5th and 95th percentiles of 5.2% to 17.0%. Compared with non-IM users, users faced a 155% higher annual Part D plan ($1067 vs $418) and 144% higher patient ($369 vs $151) costs for antidiabetic prescriptions. Conclusion Among older Part D beneficiaries using antidiabetic drugs, substantial regional variation in the use of IMs, not accounted for by sociodemographics and health status. IM use was associated with substantially greater costs for Part D plans and beneficiaries. PMID:25515869

  1. The Role of Gastrointestinal Hormones in Hepatic Lipid Metabolism

    PubMed Central

    Mells, Jamie Eugene; Anania, Frank A.

    2014-01-01

    Hepatocellular accumulation of free fatty acids (FFAs) in the form of triglycerides constitutes the metabolic basis for the development of nonalcoholic fatty liver disease (NAFLD). Recent data demonstrate that excess FFA hepatocyte storage is likely to lead to lipotoxicity and hepatocyte apoptosis. Hence, FFA-mediated hepatocyte injury is a key contributor to the pathogenesis of nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis, obesity, type 2 diabetes, essential hypertension, and other common medical problems together comprise metabolic syndrome. Evidence suggests that peptide hormones from the L cells of the distal small intestine, which comprise the core of the enteroendocrine system (EES), play two key roles, serving either as incretins, or as mediators of appetite and satiety in the central nervous system. Recent data related to glucagon-like peptide-1 (GLP-1) and other known L-cell hormones have accumulated due to the increasing frequency of bariatric surgery, which increase delivery of bile salts to the hindgut. Bile acids are a key stimulus for the TGR5 receptor of the L cells. Enhanced bile-salt flow and subsequent EES stimulation may be central to elimination of hepatic steatosis following bariatric surgery. Although GLP-1 is a clinically relevant pharmacological analogue that drives pancreatic β-cell insulin output, GLP-1 analogues also have independent benefits via their effects on hepatocellular FFA metabolism. The authors also discuss recent data regarding the role of the major peptides released by the EES, which promote satiety and modulate energy homeostasis and utilization, as well as those that control fat absorption and intestinal permeability. Taken together, elucidating novel functions for EES-related peptides and pharmacologic development of peptide analogues offer potential far-ranging treatment for obesity-related human disease. PMID:24222092

  2. Nucleon decay in GUT and nonGUT SUSY models

    SciTech Connect

    Murayama, Hitoshi

    1996-06-30

    I first emphasize the importance of searching for nucleon decay in the context of supersymmetric models. The status of minimal SUSY SU(5) model is reviewed, which can be definitively ruled out by a combination of superKamiokande andLEP-2 experiments. Non-minimal models may provide some suppression in the nucleon decay rates, but there is still a good chance for superKamiokande. I point out that the operators suppressed even by the Planck-scale are too large. We need a suppression mechanism for the operators at the level of 10-7, and the mechanism, I argue, may well be a flavor symmetry. A particular example predicts p --> K0e+ to be the dominant mode which does not arise in GUT models.

  3. Beyond the gut bacterial microbiota: The gut virome.

    PubMed

    Columpsi, Paola; Sacchi, Paolo; Zuccaro, Valentina; Cima, Serena; Sarda, Cristina; Mariani, Marcello; Gori, Andrea; Bruno, Raffaele

    2016-09-01

    The gastrointestinal tract is colonized with a highly different population of bacterial, viral, ad fungal species; viruses are reported to be dominant. The composition of gut virome is closely related to dietary habits and surrounding environment. Host and their intestinal microbes live in a dynamic equilibrium and viruses stimulate a low degree of immune responses without causing symptoms (host tolerance). However, intestinal phages could lead to a rupture of eubiosis and may contribute to the shift from health to disease in humans and animals. Viral nucleic acids and other products of lysis of bacteria serve as pathogen-associated molecular patterns (PAMPs) and could trigger specific inflammatory modulations. At the same time, phages could elicit innate antiviral immune responses. Toll-like receptors (TLRs) operated as innate antiviral immune sensors and their activation triggers signaling cascades that lead to inflammatory response. J. Med. Virol. 88:1467-1472, 2016. © 2016 Wiley Periodicals, Inc. PMID:26919534

  4. Testing GUTs: where do monopoles fit

    SciTech Connect

    Ellis, J.

    1982-10-01

    The report shows why the inadequacies of the standard model of elementary particles impel some theorists toward embedding the strong, weak and electromagnetic interactions in a simple GUT group, and explains why the grand unification scale and hence the GUM (Grand Unified Monopoles) mass are expected to be so large (greater than or equal to 10/sup 14/ GeV). It goes on to describe some model GUTs, notably minimal SU(5) and supersymmetric (susy) GUTs. The grand unified analogues of generalized Cabibbo mixing angles are introduced relevant to the prediction of baryon decay modes in different theories as well as to the Decay modes catalyzed by GUMs. Phenomenologies of conventional and susy GUTs are contrasted including the potential increase in the grand unification scale as well as possible different baryon decay modes in susy GUTs. The phenomenology of GUMs is discussed, principally their ability to catalyze baryon decays. Some of the astrophysical and cosmological constraints on GUMs, GUMs, which make it difficult to imagine ever seeing a GUM and may impose serious restrictions on GUT model-building via their behavior in the very early universe are introduced. Finally, the reasons why GUMs are crucial aspects and tests of GUTs are summarized.

  5. Arthritis susceptibility and the Gut Microbiome

    PubMed Central

    Taneja, Veena

    2014-01-01

    Summary Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors like smoking have been studies extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system that leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means. PMID:24873878

  6. Irritable Bowel Syndrome, Gut Microbiota and Probiotics

    PubMed Central

    Lee, Beom Jae

    2011-01-01

    Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression. Based on recent experimental and clinical studies, it has been suggested that additional etiological factors including low-grade inflammation, altered gut microbiota and alteration in the gut immune system play important roles in the pathogenesis of IBS. Therefore, therapeutic restoration of altered intestinal microbiota may be an ideal treatment for IBS. Probiotics are live organisms that are believed to cause no harm and result in health benefits for the host. Clinical efficacy of probiotics has been shown in the treatment or prevention of some gastrointestinal inflammation-associated disorders including traveler's diarrhea, antibiotics-associated diarrhea, pouchitis of the restorative ileal pouch and necrotizing enterocolitis. The molecular mechanisms, as cause of IBS pathogenesis, affected by altered gut microbiota and gut inflammation-immunity are reviewed. The effect of probiotics on the gut inflammation-immune systems and the results from clinical trials of probiotics for the treatment of IBS are also summarized. PMID:21860817

  7. Role of bombesin on gut mucosal growth.

    PubMed Central

    Chu, K U; Evers, B M; Ishizuka, J; Townsend, C M; Thompson, J C

    1995-01-01

    OBJECTIVE: The authors examined the effects of exogenous bombesin (BBS) on gut mucosal growth in chow-fed rats and the mucosal regeneration after gut atrophy brought about by feeding an elemental diet and after intestinal injury produced by methotrexate (MTX). SUMMARY BACKGROUND DATA: Bombesin is one of many gastrointestinal peptides implicated in the regulation of gut mucosal growth. Although BBS is known to stimulate growth of normal pancreatic tissue, the trophic effect of BBS on gut mucosa is less clear and its exact role in gut mucosal regeneration and repair is not known. METHODS: Rats were fed a regular chow diet (control) or an elemental diet plus either saline or BBS (10 micrograms/kg). In another experiment, rats fed a chow diet and treated with saline or BBS were given MTX (20 micrograms/kg) or a single intraperitoneal injection. In all experiments, small and large bowel mucosa and pancreas were removed and analyzed for BBS-mediated proliferation. RESULTS: Bombesin produced significant mucosal proliferation of the small bowel at day 14, but not at day 7, in rats fed regular chow. In contrast, BBS treatment for 7 days produced significant proliferation in both the atrophic and injured gut mucosa of rats given elemental diet or MTX. CONCLUSIONS: Bombesin may be an important enterotrophic factor for normal mucosal proliferation and may be clinically beneficial as an agent to restore or maintain gut mucosa during periods of atrophy or injury. PMID:7618976

  8. Supersymmetric F-theory GUT models

    NASA Astrophysics Data System (ADS)

    Chung, Yu-Chieh

    F-theory is a twelve-dimensional geometric version of string theory and is believed to be a natural framework for GUT model building. The aim of this dissertation is to study how gauge theories realized by F-theory can accommodate GUT models. In this dissertation, we focus on local and semi-local GUT model building in F-theory. For local GUT models, we build SU(5) GUTs by using abelian U(1) fluxes via theSU6) gauge group. Doing so, we obtain non-minimal spectra of the MSSM with doublet-triplet splitting by switching on abelian U(1)2 fluxes. We also classify all supersymmetric U(1)2 fluxes by requiring an exotic-free bulk spectrum. For semi-local GUT models, we start with an E8 singularity and obtain lower rank gauge groups by unfolding the singularity governed by spectral covers. In this framework, the spectra can be calculated by the intersection numbers of spectral covers and matter curves. In particular, we useSU4) spectral covers and abelian U(1)X fluxes to build flippedSU5) models. We show that three-generation spectra of flippedSU5) models can be achieved by turning on suitable fluxes. To construct E6 GUTs, we consider SU3) spectral covers breaking E8 down to E6. Also three-generation extended MSSM can be obtained by using non-abelian SU2) x U(1)2 fluxes.

  9. Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects.

    PubMed

    Martin, Francois-Pierre J; Rezzi, Serge; Peré-Trepat, Emma; Kamlage, Beate; Collino, Sebastiano; Leibold, Edgar; Kastler, Jürgen; Rein, Dietrich; Fay, Laurent B; Kochhar, Sunil

    2009-12-01

    Dietary preferences influence basal human metabolism and gut microbiome activity that in turn may have long-term health consequences. The present study reports the metabolic responses of free living subjects to a daily consumption of 40 g of dark chocolate for up to 14 days. A clinical trial was performed on a population of 30 human subjects, who were classified in low and high anxiety traits using validated psychological questionnaires. Biological fluids (urine and blood plasma) were collected during 3 test days at the beginning, midtime and at the end of a 2 week study. NMR and MS-based metabonomics were employed to study global changes in metabolism due to the chocolate consumption. Human subjects with higher anxiety trait showed a distinct metabolic profile indicative of a different energy homeostasis (lactate, citrate, succinate, trans-aconitate, urea, proline), hormonal metabolism (adrenaline, DOPA, 3-methoxy-tyrosine) and gut microbial activity (methylamines, p-cresol sulfate, hippurate). Dark chocolate reduced the urinary excretion of the stress hormone cortisol and catecholamines and partially normalized stress-related differences in energy metabolism (glycine, citrate, trans-aconitate, proline, beta-alanine) and gut microbial activities (hippurate and p-cresol sulfate). The study provides strong evidence that a daily consumption of 40 g of dark chocolate during a period of 2 weeks is sufficient to modify the metabolism of free living and healthy human subjects, as per variation of both host and gut microbial metabolism. PMID:19810704

  10. Gut-central nervous system axis is a target for nutritional therapies

    PubMed Central

    2012-01-01

    Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies. PMID:22490672

  11. Diet, gut microbiome, and bone health.

    PubMed

    Weaver, Connie M

    2015-04-01

    Interactions between the environment, the gut microbiome, and host characteristics that influence bone health are beginning to be explored. This is the first area where functional benefits from diet-induced changes in the gut microbiome have been reported for healthy people. Several prebiotics that reach the lower intestine have resulted in an altered gut microbiome that is thought to enhance fermentation of the fibers to produce short-chain fatty acids. These changes are positively correlated with increases in fractional calcium absorption in adolescents and with increases in measures of bone density and strength in animal models. New methodologies are available to explore mechanisms and to refine intervention strategies. PMID:25616772

  12. Mosquito gut antiparasitic and antiviral immunity.

    PubMed

    Saraiva, Raúl G; Kang, Seokyoung; Simões, Maria L; Angleró-Rodríguez, Yesseinia I; Dimopoulos, George

    2016-11-01

    Mosquitoes are responsible for the transmission of diseases with a serious impact on global human health, such as malaria and dengue. All mosquito-transmitted pathogens complete part of their life cycle in the insect gut, where they are exposed to mosquito-encoded barriers and active factors that can limit their development. Here we present the current understanding of mosquito gut immunity against malaria parasites, filarial worms, and viruses such as dengue, Chikungunya, and West Nile. The most recently proposed immune mediators involved in intestinal defenses are discussed, as well as the synergies identified between the recognition of gut microbiota and the mounting of the immune response. PMID:26827888

  13. Diet, Gut Microbiome, and Bone Health

    PubMed Central

    2016-01-01

    Interactions between the environment, the gut microbiome, and host characteristics that influence bone health are beginning to be explored. This is the first area where functional benefits from diet-induced changes in the gut microbiome have been reported for healthy people. Several prebiotics that reach the lower intestine have resulted in an altered gut microbiome that is thought to enhance fermentation of the fibers to produce short-chain fatty acids. These changes are positively correlated with increases in fractional calcium absorption in adolescents and with increases in measures of bone density and strength in animal models. New methodologies are available to explore mechanisms and to refine intervention strategies. PMID:25616772

  14. Evolution of host specialization in gut microbes: the bee gut as a model

    PubMed Central

    Kwong, Waldan K; Moran, Nancy A

    2015-01-01

    Bacterial symbionts of eukaryotes often give up generalist lifestyles to specialize to particular hosts. The eusocial honey bees and bumble bees harbor two such specialized gut symbionts, Snodgrassella alvi and Gilliamella apicola. Not only are these microorganisms specific to bees, but different strains of these bacteria tend to assort according to host species. By using in-vivo microbial transplant experiments, we show that the observed specificity is, at least in part, due to evolved physiological barriers that limit compatibility between a host and a potential gut colonizer. How and why such specialization occurs is largely unstudied for gut microbes, despite strong evidence that it is a general feature in many gut communities. Here, we discuss the potential factors that favor the evolution of host specialization, and the parallels that can be drawn with parasites and other symbiont systems. We also address the potential of the bee gut as a model for exploring gut community evolution. PMID:26011669

  15. Gut Microbiota and Extreme Longevity.

    PubMed

    Biagi, Elena; Franceschi, Claudio; Rampelli, Simone; Severgnini, Marco; Ostan, Rita; Turroni, Silvia; Consolandi, Clarissa; Quercia, Sara; Scurti, Maria; Monti, Daniela; Capri, Miriam; Brigidi, Patrizia; Candela, Marco

    2016-06-01

    The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota of highly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along with age. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae). PMID:27185560

  16. Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents.

    PubMed

    Igarashi, Miki; DiPatrizio, Nicholas V; Narayanaswami, Vidya; Piomelli, Daniele

    2015-09-01

    The gastrointestinal tract plays a critical role in the regulation of energy homeostasis by initiating neural and hormonal responses to the ingestion of nutrients. In addition to peptide hormones, such as cholecystokinin (CKK) and peptide YY (PYY), the lipid-derived mediator oleoylethanolamide (OEA) has been implicated in the control of satiety. Previous studies in humans and rodent models have shown that obesity is associated with changes in CCK, PYY and other gut-derived peptide hormones, which may contribute to decreased satiety and increased energy intake. In the present study, we show that small-intestinal OEA production is disrupted in the gut of diet-induced obese (DIO) rats and mice. In lean rodents, feeding or duodenal infusion of Intralipid® or pure oleic acid stimulates jejunal OEA mobilization. This response is strikingly absent in DIO rats and mice. Confirming previous reports, we found that feeding rats or mice a high-fat diet for 7 days is sufficient to suppress jejunal OEA mobilization. Surprisingly, a similar effect is elicited by feeding rats and mice a high-sucrose low-fat diet for 7 days. Collectively, our findings suggest that high fat-induced obesity is accompanied by alterations in the post-digestive machinery responsible for OEA biosynthesis, which may contribute to reduced satiety and hyperphagia. PMID:26024927

  17. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... medicines you take. These include: Birth control pills Hormone therapy Testosterone DHEA (a supplement) If you are ...

  18. Hormones, Women and Breast Cancer

    MedlinePlus

    ... 30 • Have used combination hormone therapy (estrogen plus progestin) for more than five years • Have a mother, ... know that estrogen (the major female hormone) and progestin (a synthetic form of progesterone, another female hormone) ...

  19. Hormone therapy for prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing ... helps slow the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. ...

  20. [The gut microbiota in sickness and health].

    PubMed

    Lankelma, Jacqueline M; Nieuwdorp, Max; de Vos, Willem M; Wiersinga, W Joost

    2014-01-01

    The human gut microbiota, formerly known as 'gut flora', may be regarded as an external organ with many physiological functions in metabolism, development of the immune system and defense against pathogens. The adult gut microbiota consist of 1013-1014 micro-organisms. The aggregate genome of these, known as the microbiome, is 100 times larger than the human genome. The gut microbiotica may be involved in the pathogenesis of a range of syndromes, such as inflammatory bowel disease, obesity, diabetes mellitus and atopic disorders. It should be noted that until now most of the studies conducted have been association studies, without proof of causality. This increasing insight has led to identification of new therapeutic strategies, which are currently being investigated in clinical studies. Although the implications of this knowledge for individual patients have yet to become clear, various interventions are conceivable, such as supplementation of nutritional elements, prebiotics or probiotics and feces transplantation. PMID:24780568

  1. Villification: How the Gut Gets Its Villi

    PubMed Central

    Shyer, Amy E.; Tallinen, Tuomas; Nerurkar, Nandan L.; Wei, Zhiyan; Gil, Eun Seok; Kaplan, David L.; Tabin, Clifford J.; Mahadevan, L.

    2014-01-01

    The villi of the human and chick gut are formed in similar step-wise progressions, wherein the mesenchyme and attached epithelium first fold into longitudinal ridges, then a zigzag pattern, and finally individual villi. We find that these steps of villification depend upon the sequential differentiation of the distinct smooth muscle layers of the gut, which restrict the expansion of the growing endoderm and mesenchyme, generating compressive stresses that lead to their buckling and folding. A quantitative computational model, incorporating measured properties of the developing gut, recapitulates the morphological patterns seen during villification in a variety of species. These results provide a mechanistic understanding of the formation of these elaborations of the lining of the gut, essential for providing sufficient surface area for nutrient absorption. PMID:23989955

  2. Gut microbial communities of social bees.

    PubMed

    Kwong, Waldan K; Moran, Nancy A

    2016-06-01

    The gut microbiota can have profound effects on hosts, but the study of these relationships in humans is challenging. The specialized gut microbial community of honey bees is similar to the mammalian microbiota, as both are mostly composed of host-adapted, facultatively anaerobic and microaerophilic bacteria. However, the microbial community of the bee gut is far simpler than the mammalian microbiota, being dominated by only nine bacterial species clusters that are specific to bees and that are transmitted through social interactions between individuals. Recent developments, which include the discovery of extensive strain-level variation, evidence of protective and nutritional functions, and reports of eco-physiological or disease-associated perturbations to the microbial community, have drawn attention to the role of the microbiota in bee health and its potential as a model for studying the ecology and evolution of gut symbionts. PMID:27140688

  3. [Multiple Sclerosis and Commensal Gut Flora].

    PubMed

    Yamamura, Takashi

    2016-06-01

    Although a symbiotic relationship between commensal gut microbiota and host is widely appreciated, recent works have indicated that normal gut flora functions to prevent inflammatory bowel diseases and obesity in the host, indicating a more mutualistic relationship. Dysbiosis of the commensal flora may lead to development of these disorders. Studies using experimental auto immune encephalomyelitis (EAE), a rodent model for studying multiple sclerosis (MS), revealed that onset of MS may be triggered by dysbiosis in the gut. We recently revealed a significant reduction in certain clostridia strains, which probably function to induce regulatory T cells, in the gut microbiota of patients with MS. Results from this study should be consideved when designing strategies for the prevention and treatment of MS. PMID:27279159

  4. Effects of Antibiotics on Gut Microbiota.

    PubMed

    Lange, Kathleen; Buerger, Martin; Stallmach, Andreas; Bruns, Tony

    2016-01-01

    The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease. PMID:27028893

  5. Go with your gut: microbiota meet microglia

    PubMed Central

    Mosher, Kira Irving; Wyss-Coray, Tony

    2016-01-01

    Discovering the environmental factors that control microglia is key to understanding and managing brain health. A new study finds that microbiota in the gut are essential for regulating microglia maturation and activation. PMID:26108718

  6. Gut-liver axis and sensing microbes.

    PubMed

    Szabo, Gyongyi; Bala, Shashi; Petrasek, Jan; Gattu, Arijeet

    2010-01-01

    'Detoxification' of gut-derived toxins and microbial products from gut-derived microbes is a major role of the liver. While the full repertoire of gut-derived microbial products that reach the liver in health and disease is yet to be explored, the levels of bacterial lipopolysaccharide (LPS), a component of Gram-negative bacteria, is increased in the portal and/or systemic circulation in several types of chronic liver diseases. Increased gut permeability and LPS play a role in alcoholic liver disease where alcohol impairs the gut epithelial integrity through alterations in tight junction proteins. In addition, non-alcoholic fatty liver disease is also associated with increased serum LPS levels and activation of the pro-inflammatory cascade plays a central role in disease progression. Microbial danger signals are recognized by pattern recognition receptors such as the Toll-like receptor 4 (TLR4). Increasing evidence suggests that TLR4-mediated signaling via the MyD88-dependent or MyD88-independent pathways may play different roles in liver diseases associated with increased LPS exposure of the liver as a result of gut permeability. For example, we showed that in alcoholic liver disease, the MyD88-independent, IRF3-dependent TLR4 cascade plays a role in steatosis and inflammation. Our recent data demonstrate that chronic alcohol exposure in the liver leads to sensitization of Kupffer cells to LPS via a mechanism involving upregulation of microRNA-155 in Kupffer cells. Thus, understanding the cell-specific recognition and intracellular signaling events in sensing gut-derived microbes will help to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. PMID:21525758

  7. Routine OGTT: A Robust Model Including Incretin Effect for Precise Identification of Insulin Sensitivity and Secretion in a Single Individual

    PubMed Central

    De Gaetano, Andrea; Panunzi, Simona; Matone, Alice; Samson, Adeline; Vrbikova, Jana; Bendlova, Bela; Pacini, Giovanni

    2013-01-01

    In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating glucose-driven insulin secretion) has been developed. OGTT data from 78 patients in five different glucose tolerance groups were analyzed: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IFG+IGT, and Type 2 Diabetes Mellitus (T2DM). A comparison with the 2011 Salinari (COntinuos GI tract MOdel, COMO) and the 2002 Dalla Man (Dalla Man MOdel, DMMO) models was made with particular attention to insulin sensitivity indices ISCOMO, ISDMMO and kxgi (the insulin sensitivity index for SIMO). ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10−5±9.36×10−5 min−1pM−1), IFG (5.30×10−5±5.18×10−5) and combined IGT, IFG+IGT and T2DM (2.09×10−5±1.95×10−5, 2.38×10−5±2.28×10−5 and 2.38×10−5±2.09×10−5 respectively). No significance was obtained when comparing ISCOMO or ISDMMO across groups. Moreover, kxgi presented the lowest sample average coefficient of variation over the five groups (25.43%), with average CVs for ISCOMO and ISDMMO of 70.32% and 57.75% respectively; kxgi also presented the strongest correlations with all considered empirical measures of insulin sensitivity. While COMO and DMMO appear over-parameterized for fitting single-subject clinical OGTT data, SIMO provides a robust, precise, physiologically plausible estimate of insulin sensitivity, with which habitual empirical insulin sensitivity indices correlate well. The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically

  8. Routine OGTT: a robust model including incretin effect for precise identification of insulin sensitivity and secretion in a single individual.

    PubMed

    De Gaetano, Andrea; Panunzi, Simona; Matone, Alice; Samson, Adeline; Vrbikova, Jana; Bendlova, Bela; Pacini, Giovanni

    2013-01-01

    In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating glucose-driven insulin secretion) has been developed. OGTT data from 78 patients in five different glucose tolerance groups were analyzed: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IFG+IGT, and Type 2 Diabetes Mellitus (T2DM). A comparison with the 2011 Salinari (COntinuos GI tract MOdel, COMO) and the 2002 Dalla Man (Dalla Man MOdel, DMMO) models was made with particular attention to insulin sensitivity indices ISCOMO, ISDMMO and kxgi (the insulin sensitivity index for SIMO). ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10(-5)±9.36×10(-5) min(-1)pM(-1)), IFG (5.30×10(-5)±5.18×10(-5)) and combined IGT, IFG+IGT and T2DM (2.09×10(-5)±1.95×10(-5), 2.38×10(-5)±2.28×10(-5) and 2.38×10(-5)±2.09×10(-5) respectively). No significance was obtained when comparing ISCOMO or ISDMMO across groups. Moreover, kxgi presented the lowest sample average coefficient of variation over the five groups (25.43%), with average CVs for ISCOMO and ISDMMO of 70.32% and 57.75% respectively; kxgi also presented the strongest correlations with all considered empirical measures of insulin sensitivity. While COMO and DMMO appear over-parameterized for fitting single-subject clinical OGTT data, SIMO provides a robust, precise, physiologically plausible estimate of insulin sensitivity, with which habitual empirical insulin sensitivity indices correlate well. The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically

  9. Role of Gut Microbiota in Liver Disease.

    PubMed

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism. PMID:26447960

  10. Seasonal Variation in Human Gut Microbiome Composition

    PubMed Central

    Davenport, Emily R.; Mizrahi-Man, Orna; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2014-01-01

    The composition of the human gut microbiome is influenced by many environmental factors. Diet is thought to be one of the most important determinants, though we have limited understanding of the extent to which dietary fluctuations alter variation in the gut microbiome between individuals. In this study, we examined variation in gut microbiome composition between winter and summer over the course of one year in 60 members of a founder population, the Hutterites. Because of their communal lifestyle, Hutterite diets are similar across individuals and remarkably stable throughout the year, with the exception that fresh produce is primarily served during the summer and autumn months. Our data indicate that despite overall gut microbiome stability within individuals over time, there are consistent and significant population-wide shifts in microbiome composition across seasons. We found seasonal differences in both (i) the abundance of particular taxa (false discovery rate <0.05), including highly abundant phyla Bacteroidetes and Firmicutes, and (ii) overall gut microbiome diversity (by Shannon diversity; P = 0.001). It is likely that the dietary fluctuations between seasons with respect to produce availability explain, at least in part, these differences in microbiome composition. For example, high levels of produce containing complex carbohydrates consumed during the summer months might explain increased abundance of Bacteroidetes, which contain complex carbohydrate digesters, and decreased levels of Actinobacteria, which have been negatively correlated to fiber content in food questionnaires. Our observations demonstrate the plastic nature of the human gut microbiome in response to variation in diet. PMID:24618913

  11. The Gut Microbiome in the NOD Mouse.

    PubMed

    Peng, Jian; Hu, Youjia; Wong, F Susan; Wen, Li

    2016-01-01

    The microbiome (or microbiota) are an ecological community of commensal, symbiotic, and pathogenic microorganisms that outnumber the cells of the human body tenfold. These microorganisms are most abundant in the gut where they play an important role in health and disease. Alteration of the homeostasis of the gut microbiota can have beneficial or harmful consequences to health. There has recently been a major increase in studies on the association of the gut microbiome composition with disease phenotypes.The nonobese diabetic (NOD) mouse is an excellent mouse model to study spontaneous type 1 diabetes development. We, and others, have reported that gut bacteria are critical modulators for type 1 diabetes development in genetically susceptible NOD mice.Here we present our standard protocol for gut microbiome analysis in NOD mice that has been routinely implemented in our research laboratory. This incorporates the following steps: (1) Isolation of total DNA from gut bacteria from mouse fecal samples or intestinal contents; (2) bacterial DNA sequencing, and (3) basic data analysis. PMID:27032947

  12. Microbiota and the gut-brain axis.

    PubMed

    Bienenstock, John; Kunze, Wolfgang; Forsythe, Paul

    2015-08-01

    Changes in gut microbiota can modulate the peripheral and central nervous systems, resulting in altered brain functioning, and suggesting the existence of a microbiota gut-brain axis. Diet can also change the profile of gut microbiota and, thereby, behavior. Effects of bacteria on the nervous system cannot be disassociated from effects on the immune system since the two are in constant bidirectional communication. While the composition of the gut microbiota varies greatly among individuals, alterations to the balance and content of common gut microbes may affect the production of molecules such as neurotransmitters, e.g., gamma amino butyric acid, and the products of fermentation, e.g., the short chain fatty acids butyrate, propionate, and acetate. Short chain fatty acids, which are pleomorphic, especially butyrate, positively influence host metabolism by promoting glucose and energy homeostasis, regulating immune responses and epithelial cell growth, and promoting the functioning of the central and peripheral nervous systems. In the future, the composition, diversity, and function of specific probiotics, coupled with similar, more detailed knowledge about gut microbiota, will potentially help in developing more effective diet- and drug-based therapies. PMID:26175487

  13. Gut microbiota in autism and mood disorders

    PubMed Central

    Mangiola, Francesca; Ianiro, Gianluca; Franceschi, Francesco; Fagiuoli, Stefano; Gasbarrini, Giovanni; Gasbarrini, Antonio

    2016-01-01

    The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders. PMID:26755882

  14. [Why could gut microbiota become a medication?].

    PubMed

    Bourlioux, P; Megerlin, F; Corthier, G; Gobert, J-G; Butel, M-J

    2014-09-01

    The gut microbiota (or gut flora) is a set of bacteria living in symbiosis with the host. Strictly associated with the intestinal tract and interacting with it, the gut microbiota is not a tissue nor an organ, but a supra-organism. A disruption of dialogue between bacteria and human cells is a risk factor or a possible cause of various diseases. The restoration of this dialogue, thanks to the transfer of the gut microbiota of a healthy individual to a patient whose balance of gut flora has been broken, is a new therapeutic approach. If its exact effect still eludes scientific understanding, its clinical benefit is well established for an indication, and is recently being tested for many others. The proven contribution of gut microbiota in the human physiological balance calls for intensifying research throughout the world about the state of knowledge and technologies, as well as on the legal and ethical dimension of fecal microbiota transfer. This didactic paper updates the questions in relation with this therapeutic act. PMID:25220228

  15. Probiotics, Prebiotics, and Synbiotics: Gut and Beyond

    PubMed Central

    Vyas, Usha; Ranganathan, Natarajan

    2012-01-01

    The human intestinal tract has been colonized by thousands of species of bacteria during the coevolution of man and microbes. Gut-borne microbes outnumber the total number of body tissue cells by a factor of ten. Recent metagenomic analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the tissues in the entire human body. Evidence for various beneficial roles of the intestinal microbiota in human health and disease is expanding rapidly. Perturbation of the intestinal microbiota may lead to chronic diseases such as autoimmune diseases, colon cancers, gastric ulcers, cardiovascular disease, functional bowel diseases, and obesity. Restoration of the gut microbiota may be difficult to accomplish, but the use of probiotics has led to promising results in a large number of well-designed (clinical) studies. Microbiomics has spurred a dramatic increase in scientific, industrial, and public interest in probiotics and prebiotics as possible agents for gut microbiota management and control. Genomics and bioinformatics tools may allow us to establish mechanistic relationships among gut microbiota, health status, and the effects of drugs in the individual. This will hopefully provide perspectives for personalized gut microbiota management. PMID:23049548

  16. Xylooligosaccharide supplementation alters gut bacteria in both healthy and prediabetic adults: a pilot study

    PubMed Central

    Yang, Jieping; Summanen, Paula H.; Henning, Susanne M.; Hsu, Mark; Lam, Heiman; Huang, Jianjun; Tseng, Chi-Hong; Dowd, Scot E.; Finegold, Sydney M.; Heber, David; Li, Zhaoping

    2015-01-01

    Background: It has been suggested that gut microbiota is altered in Type 2 Diabetes Mellitus (T2DM) patients. Objective: This study was to evaluate the effect of the prebiotic xylooligosaccharide (XOS) on the gut microbiota in both healthy and prediabetic (Pre-DM) subjects, as well as impaired glucose tolerance (IGT) in Pre-DM. Subjects/Methods: Pre-DM (n = 13) or healthy (n = 16) subjects were randomized to receive 2 g/day XOS or placebo for 8-weeks. In Pre-DM subjects, body composition and oral glucose tolerance test (OGTT) was done at baseline and week 8. Stool from Pre-DM and healthy subjects at baseline and week 8 was analyzed for gut microbiota characterization using Illumina MiSeq sequencing. Results: We identified 40 Pre-DM associated bacterial taxa. Among them, the abundance of the genera Enterorhabdus, Howardella, and Slackia was higher in Pre-DM. XOS significantly decreased or reversed the increase in abundance of Howardella, Enterorhabdus, and Slackia observed in healthy or Pre-DM subjects. Abundance of the species Blautia hydrogenotrophica was lower in pre-DM subjects, while XOS increased its abundance. In Pre-DM, XOS showed a tendency to reduce OGTT 2-h insulin levels (P = 0.13), but had no effect on body composition, HOMA-IR, serum glucose, triglyceride, satiety hormones, and TNFα. Conclusion: This is the first clinical observation of modifications of the gut microbiota by XOS in both healthy and Pre-DM subjects in a pilot study. Prebiotic XOS may be beneficial in reversing changes in the gut microbiota during the development of diabetes. Clinical trial registration: NCT01944904 (https://clinicaltrials.gov/ct2/show/NCT01944904). PMID:26300782

  17. GLP-1, the Gut-Brain, and Brain-Periphery Axes

    PubMed Central

    Cabou, Cendrine; Burcelin, Remy

    2011-01-01

    Glucagon-like peptide 1 (GLP-1) is a gut hormone which directly binds to the GLP-1 receptor located at the surface of the pancreatic β-cells to enhance glucose-induced insulin secretion. In addition to its pancreatic effects, GLP-1 can induce metabolic actions by interacting with its receptors expressed on nerve cells in the gut and the brain. GLP-1 can also be considered as a neuropeptide synthesized by neuronal cells in the brain stem that release the peptide directly into the hypothalamus. In this environment, GLP-1 is assumed to control numerous metabolic and cardiovascular functions such as insulin secretion, glucose production and utilization, and arterial blood flow. However, the exact roles of these two locations in the regulation of glucose homeostasis are not well understood. In this review, we highlight the latest experimental data supporting the role of the gut-brain and brain-periphery axes in the control of glucose homeostasis. We also focus our attention on the relevance of β-cell and brain cell targeting by gut GLP-1 for the regulation of glucose homeostasis. In addition to its action on β-cells, we find that understanding the physiological role of GLP-1 will help to develop GLP-1-based therapies to control glycemia in type 2 diabetes by triggering the gut-brain axis or the brain directly. This pleiotropic action of GLP-1 is an important concept that may help to explain the observation that, during their treatment, type 2 diabetic patients can be identified as 'responders' and 'non-responders'. PMID:22262078

  18. Growth Hormone Promotes Lymphangiogenesis

    PubMed Central

    Banziger-Tobler, Nadja Erika; Halin, Cornelia; Kajiya, Kentaro; Detmar, Michael

    2008-01-01

    The lymphatic system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined using comparative transcriptional profiling studies of cultured lymphatic endothelial cells versus blood vascular endothelial cells, growth hormone receptor was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Growth hormone induced in vitro proliferation, sprouting, tube formation, and migration of lymphatic endothelial cells, and the mitogenic effect was independent of vascular endothelial growth factor receptor-2 or -3 activation. Growth hormone also inhibited serum starvation-induced lymphatic endothelial cell apoptosis. No major alterations of lymphatic vessels were detected in the normal skin of bovine growth hormone-transgenic mice. However, transgenic delivery of growth hormone accelerated lymphatic vessel ingrowth into the granulation tissue of full-thickness skin wounds, and intradermal delivery of growth hormone resulted in enlargement and enhanced proliferation of cutaneous lymphatic vessels in wild-type mice. These results identify growth hormone as a novel lymphangiogenic factor. PMID:18583315

  19. Thyroid Hormone and Cardioprotection.

    PubMed

    Gerdes, Anthony Martin; Ojamaa, Kaie

    2016-01-01

    The heart is a major target of thyroid hormones, with maintenance of euthyroid hormone balance critical for proper function. In particular, chronic low thyroid function can eventually lead to dilated heart failure with impaired coronary blood flow. New evidence also suggests that heart diseases trigger a reduction in cardiac tissue thyroid hormone levels, a condition that may not be detectible using serum hormone assays. Many animal and clinical studies have demonstrated a high prevalence of low thyroid function in heart diseases with worse outcomes from this condition. Animal and human studies have also demonstrated many benefits from thyroid hormone treatment of heart diseases, particularly heart failure. Nonetheless, this potential treatment has not yet translated to patients due to a number of important concerns. The most serious concern involves the potential of accidental overdose leading to increased arrhythmias and sudden death. Several important clinical studies, which actually used excessive doses of thyroid hormone analogs, have played a major role in convincing the medical community that thyroid hormones are simply too dangerous to be considered for treatment in cardiac patients. Nonetheless, this issue has not gone away due primarily to overwhelmingly positive evidence for treatment benefits and a new understanding of the cellular and molecular mechanisms underlying those benefits. This review will first discuss the clinical evidence for the use of thyroid hormones as a cardioprotective agent and then provide an overview of the cellular and molecular mechanisms underlying beneficial changes from thyroid hormone treatment of heart diseases. © 2016 American Physiological Society. Compr Physiol 6:1199-1219, 2016. PMID:27347890

  20. Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells.

    PubMed

    Velasco, Myrian; Díaz-García, Carlos Manlio; Larqué, Carlos; Hiriart, Marcia

    2016-09-01

    Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (KATP) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na(+) channels (Nav) and subsequently voltage-dependent Ca(2+) channels (Cav). The increase in intracellular Ca(2+) triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (KATP, Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion. PMID:27436126

  1. It's a gut feeling: how the gut microbiota affects the state of mind.

    PubMed

    Farmer, Adam D; Randall, Holly A; Aziz, Qasim

    2014-07-15

    Common human experience shows that stress and anxiety may modulate gut function. Such observations have been combined with an increasing evidence base that has culminated in the concept of the brain-gut axis. Nevertheless, it has not been until recently that the gut and its attendant components have been considered to influence higher cerebral function and behaviour per se. Moreover, the proposal that the gut and the bacteria contained therein (collectively referred to as the microbiota) can modulate mood and behaviours, has an increasing body of supporting evidence, albeit largely derived from animal studies. The gut microbiota is a dynamic and diverse ecosystem and forms a symbiotic relationship with the host. Herein we describe the components of the gut microbiota and mechanisms by which it can influence neural development, complex behaviours and nociception. Furthermore, we propose the novel concept of a 'state of gut' rather than a state of mind, particularly in relation to functional bowel disorders. Finally, we address the exciting possibility that the gut microbiota may offer a novel area of therapeutic intervention across a diverse array of both affective and gastrointestinal disorders. PMID:24665099

  2. Immunology of Gut Mucosal Vaccines

    PubMed Central

    Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

    2011-01-01

    Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

  3. Gut microbiota, probiotics and diabetes

    PubMed Central

    2014-01-01

    Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes. PMID:24939063

  4. Treating type 1 diabetes: from strategies for insulin delivery to dual hormonal control

    PubMed Central

    McCall, A. L.; Farhy, L. S.

    2014-01-01

    Type 1 diabetes is a disorder where slow destruction of pancreatic β-cells occurs through autoimmune mechanisms. The result is a progressive and ultimately complete lack of endogenous insulin. Due to β-cell lack, secondary abnormalities in glucagon and likely in incretins occur. These multiple hormonal abnormalities cause metabolic instability and extreme glycemic variability, which is the primary phenotype. As the disease progresses patients often develop hypoglycemia unawareness and defects in their counterregulatory defenses. Intensive insulin therapy may thus lead to 3-fold excess of severe hypoglycemia and severely hinder the effective and safe control of hyperglycemia. The main goal of the therapy for type 1 diabetes has long been physiological mimicry of normal insulin secretion based on monitoring which requires considerable effort and understanding of the underlying physiology. Attainment of this goal is challenged by the nature of the disease and our current lack of means to fully repair the abnormal endocrine pancreas interactive functions. As a result, various insulin preparations has been developed to partially compensate for the inability to deliver timely exogenous insulin directly to the portal/intrapancreatic circulation. It remains an ongoing task to identify the ideal routes and regimens of their delivery and potentially that of other hormones to restore the deficient and disordered hormonal environment of the pancreas to achieve a near normal metabolic state. Several recent technological advances help addressing these goals, including the rapid progress in insulin pumps, continuous glucose sensors, and ultimately the artificial pancreas closed-loop technology and the recent start of dual-hormone therapies. PMID:23732369

  5. Bioidentical Hormones and Menopause

    MedlinePlus

    ... There are two types of bioidentical hormone products: • Pharmaceutical products. These products have been approved by the ... made products. These are made in a compounding pharmacy (a pharmacy that mixes medications according to a ...

  6. Bioidentical Hormones and Menopause

    MedlinePlus

    ... There are two types of bioidentical hormone products: Pharmaceutical products . These products have been approved by the ... made products. These are made in a compounding pharmacy(a pharmacy that mixes medications according to a ...

  7. Thyroid Hormone Treatment

    MedlinePlus

    ... is to closely replicate normal thyroid functioning. Pure, synthetic thyroxine (T4) works in the same way as ... needing thyroid hormone replacement (see Hypothyroidism brochure ). Pure synthetic thyroxine (T4), taken once daily by mouth, successfully ...

  8. Growth hormone stimulation test

    MedlinePlus

    The growth hormone (GH) stimulation test measures the ability of the body to produce GH. ... killing medicine (antiseptic). The first sample is drawn early in the morning. Medicine is given through the ...

  9. Endocrine Glands & Their Hormones

    MedlinePlus

    ... Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Endocrine System » Endocrine Glands & Their Hormones Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life Process Anatomical Terminology Review Quiz ...

  10. Autoimmunity against thyroid hormones.

    PubMed

    Sakata, S

    1994-01-01

    The presence of thyroid hormone autoantibodies (THAA) is a common phenomenon. More than 270 cases have been reported by the end of 1993 involving not only thyroidal but also nonthyroidal disorders. Clinically, THAA in a patient's serum produces variation in thyroid hormone metabolism and, in particular, may interfere with the radioimmunoassay (RIA) results of total or free thyroid hormone measurements, which can cause unusually high or low values of the hormones depending on the B/F separation method used. This in vitro interference can give clinicians confusing information about the patient's thyroid state. As a result, the patient may receive inappropriate treatment from physicians who are unaware of this disorder. The presence of THAA has been reported not only in humans but also in dogs, chickens, and rats. In this review article, clinical features of THAA and the mechanism of autoantibody production are discussed. PMID:7535535

  11. Vaginal bleeding - hormonal

    MedlinePlus

    ... taken just before the period starts Women over age 40 and older may have the option to receive cyclic progestin or cyclic hormone therapy. A health care provider may recommend iron supplements for women with anemia. If you want ...

  12. Nonalcoholic Fatty Liver Disease and the Gut Microbiome.

    PubMed

    Boursier, Jerome; Diehl, Anna Mae

    2016-05-01

    Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipoprotein lipase induction, alteration of bile acid profile, endogenous alcohol production, or liver inflammation secondary to endotoxemia result from gut dysbiosis. Modulation of the gut microbiota by pre/probiotics gives promising results in animal, but needs to be evaluated in human before use in clinical practice. Gut microbiota adds complexity to the pathophysiology of nonalcoholic fatty liver disease but represents an opportunity to discover new therapeutic targets. PMID:27063268

  13. Convergence of gut microbiomes in myrmecophagous mammals.

    PubMed

    Delsuc, Frédéric; Metcalf, Jessica L; Wegener Parfrey, Laura; Song, Se Jin; González, Antonio; Knight, Rob

    2014-03-01

    Mammals have diversified into many dietary niches. Specialized myrmecophagous (ant- and termite-eating) placental mammals represent a textbook example of evolutionary convergence driven by extreme diet specialization. Armadillos, anteaters, aardvarks, pangolins and aardwolves thus provide a model system for understanding the potential role of gut microbiota in the convergent adaptation to myrmecophagy. Here, we expand upon previous mammalian gut microbiome studies by using high-throughput barcoded Illumina sequencing of the 16S rRNA gene to characterize the composition of gut microbiota in 15 species representing all placental myrmecophagous lineages and their close relatives from zoo- and field-collected samples. We confirm that both diet and phylogeny drive the evolution of mammalian gut microbiota, with cases of convergence in global composition, but also examples of phylogenetic inertia. Our results reveal specialized placental myrmecophages as a spectacular case of large-scale convergence in gut microbiome composition. Indeed, neighbour-net networks and beta-diversity plots based on UniFrac distances show significant clustering of myrmecophagous species (anteaters, aardvarks and aardwolves), even though they belong to phylogenetically distant lineages representing different orders. The aardwolf, which diverged from carnivorous hyenas only in the last 10 million years, experienced a convergent shift in the composition of its gut microbiome to become more similar to other myrmecophages. These results confirm diet adaptation to be a major driving factor of convergence in gut microbiome composition over evolutionary timescales. This study sets the scene for future metagenomic studies aiming at evaluating potential convergence in functional gene content in the microbiomes of specialized mammalian myrmecophages. PMID:24118574

  14. Circadian rhythms, alcohol and gut interactions

    PubMed Central

    Forsyth, Christopher B.; Voigt, Rbin M.; Burgess, Helen J.; Swanson, Garth R.; Keshavarzian, Ali

    2015-01-01

    The circadian clock establishes rhythms throughout the body with an approximately 24 hour period that affect expression of hundreds of genes. Epidemiological data reveal chronic circadian misalignment, common in our society, significantly increases the risk for a myriad of diseases, including cardiovascular disease, diabetes, cancer, infertility and gastrointestinal disease. Disruption of intestinal barrier function, also known as gut leakiness, is especially important in alcoholic liver disease (ALD). Several studies have shown that alcohol causes ALD in only a 20–30% subset of alcoholics. Thus, a better understanding is needed of why only a subset of alcoholics develops ALD. Compelling evidence shows that increased gut leakiness to microbial products and especially LPS play a critical role in the pathogenesis of ALD. Clock and other circadian clock genes have been shown to regulate lipid transport, motility and other gut functions. We hypothesized that one possible mechanism for alcohol-induced intestinal hyper-permeability is through disruption of central or peripheral (intestinal) circadian regulation. In support of this hypothesis, our recent data shows that disruption of circadian rhythms makes the gut more susceptible to injury. Our in vitro data show that alcohol stimulates increased Clock and Per2 circadian clock proteins and that siRNA knockdown of these proteins prevents alcohol-induced permeability. We also show that intestinal Cyp2e1-mediated oxidative stress is required for alcohol-induced upregulation of Clock and Per2 and intestinal hyperpermeability. Our mouse model of chronic alcohol feeding shows that circadian disruption through genetics (in ClockΔ19 mice) or environmental disruption by weekly 12h phase shifting results in gut leakiness alone and exacerbates alcohol-induced gut leakiness and liver pathology. Our data in human alcoholics show they exhibit abnormal melatonin profiles characteristic of circadian disruption. Taken together our

  15. Protein Hormones and Immunity‡

    PubMed Central

    Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron

    2007-01-01

    A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and

  16. Constrained Sypersymmetric Flipped SU (5) GUT Phenomenology

    SciTech Connect

    Ellis, John; Mustafayev, Azar; Olive, Keith A.; /Minnesota U., Theor. Phys. Inst. /Minnesota U. /Stanford U., Phys. Dept. /SLAC

    2011-08-12

    We explore the phenomenology of the minimal supersymmetric flipped SU(5) GUT model (CFSU(5)), whose soft supersymmetry-breaking (SSB) mass parameters are constrained to be universal at some input scale, Min, above the GUT scale, M{sub GUT}. We analyze the parameter space of CFSU(5) assuming that the lightest supersymmetric particle (LSP) provides the cosmological cold dark matter, paying careful attention to the matching of parameters at the GUT scale. We first display some specific examples of the evolutions of the SSB parameters that exhibit some generic features. Specifically, we note that the relationship between the masses of the lightest neutralino {chi} and the lighter stau {tilde {tau}}{sub 1} is sensitive to M{sub in}, as is the relationship between m{sub {chi}} and the masses of the heavier Higgs bosons A,H. For these reasons, prominent features in generic (m{sub 1/2}, m{sub 0}) planes such as coannihilation strips and rapid-annihilation funnels are also sensitive to Min, as we illustrate for several cases with tan {beta} = 10 and 55. However, these features do not necessarily disappear at large Min, unlike the case in the minimal conventional SU(5) GUT. Our results are relatively insensitive to neutrino masses.

  17. Gut/brain axis and the microbiota.

    PubMed

    Mayer, Emeran A; Tillisch, Kirsten; Gupta, Arpana

    2015-03-01

    Tremendous progress has been made in characterizing the bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. A series of provocative preclinical studies have suggested a prominent role for the gut microbiota in these gut-brain interactions. Based on studies using rodents raised in a germ-free environment, the gut microbiota appears to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems. Additionally, microbiota perturbations by probiotics and antibiotics exert modulatory effects on some of these measures in adult animals. Current evidence suggests that multiple mechanisms, including endocrine and neurocrine pathways, may be involved in gut microbiota-to-brain signaling and that the brain can in turn alter microbial composition and behavior via the autonomic nervous system. Limited information is available on how these findings may translate to healthy humans or to disease states involving the brain or the gut/brain axis. Future research needs to focus on confirming that the rodent findings are translatable to human physiology and to diseases such as irritable bowel syndrome, autism, anxiety, depression, and Parkinson's disease. PMID:25689247

  18. Childhood Obesity: A Role for Gut Microbiota?

    PubMed Central

    Sanchez, Marina; Panahi, Shirin; Tremblay, Angelo

    2014-01-01

    Obesity is a serious public health issue affecting both children and adults. Prevention and management of obesity is proposed to begin in childhood when environmental factors exert a long-term effect on the risk for obesity in adulthood. Thus, identifying modifiable factors may help to reduce this risk. Recent evidence suggests that gut microbiota is involved in the control of body weight, energy homeostasis and inflammation and thus, plays a role in the pathophysiology of obesity. Prebiotics and probiotics are of interest because they have been shown to alter the composition of gut microbiota and to affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community. As shown in this review, prebiotics and probiotics have physiologic functions that contribute to changes in the composition of gut microbiota, maintenance of a healthy body weight and control of factors associated with childhood obesity through their effects on mechanisms controlling food intake, fat storage and alterations in gut microbiota. PMID:25546278

  19. The Gut Microbiota: Ecology and Function

    SciTech Connect

    Willing, B.P.; Jansson, J.K.

    2010-06-01

    The gastrointestinal (GI) tract is teeming with an extremely abundant and diverse microbial community. The members of this community have coevolved along with their hosts over millennia. Until recently, the gut ecosystem was viewed as black box with little knowledge of who or what was there or their specific functions. Over the past decade, however, this ecosystem has become one of fastest growing research areas of focus in microbial ecology and human and animal physiology. This increased interest is largely in response to studies tying microbes in the gut to important diseases afflicting modern society, including obesity, allergies, inflammatory bowel diseases, and diabetes. Although the importance of a resident community of microorganisms in health was first hypothesized by Pasteur over a century ago (Sears, 2005), the multiplicity of physiological changes induced by commensal bacteria has only recently been recognized (Hooper et al., 2001). The term 'ecological development' was recently coined to support the idea that development of the GI tract is a product of the genetics of the host and the host's interactions with resident microbes (Hooper, 2004). The search for new therapeutic targets and disease biomarkers has escalated the need to understand the identities and functions of the microorganisms inhabiting the gut. Recent studies have revealed new insights into the membership of the gut microbial community, interactions within that community, as well as mechanisms of interaction with the host. This chapter focuses on the microbial ecology of the gut, with an emphasis on information gleaned from recent molecular studies.

  20. Engineering the gut microbiota to treat hyperammonemia

    PubMed Central

    Shen, Ting-Chin David; Albenberg, Lindsey; Bittinger, Kyle; Chehoud, Christel; Chen, Ying-Yu; Judge, Colleen A.; Chau, Lillian; Ni, Josephine; Sheng, Michael; Lin, Andrew; Wilkins, Benjamin J.; Buza, Elizabeth L.; Lewis, James D.; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Bushman, Frederic D.; Wu, Gary D.

    2015-01-01

    Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility. PMID:26098218

  1. Engineering the gut microbiota to treat hyperammonemia.

    PubMed

    Shen, Ting-Chin David; Albenberg, Lindsey; Bittinger, Kyle; Chehoud, Christel; Chen, Ying-Yu; Judge, Colleen A; Chau, Lillian; Ni, Josephine; Sheng, Michael; Lin, Andrew; Wilkins, Benjamin J; Buza, Elizabeth L; Lewis, James D; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Bushman, Frederic D; Wu, Gary D

    2015-07-01

    Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility. PMID:26098218

  2. Host adaptive immunity alters gut microbiota.

    PubMed

    Zhang, Husen; Sparks, Joshua B; Karyala, Saikumar V; Settlage, Robert; Luo, Xin M

    2015-03-01

    It has long been recognized that the mammalian gut microbiota has a role in the development and activation of the host immune system. Much less is known on how host immunity regulates the gut microbiota. Here we investigated the role of adaptive immunity on the mouse distal gut microbial composition by sequencing 16 S rRNA genes from microbiota of immunodeficient Rag1(-/-) mice, versus wild-type mice, under the same housing environment. To detect possible interactions among immunological status, age and variability from anatomical sites, we analyzed samples from the cecum, colon, colonic mucus and feces before and after weaning. High-throughput sequencing showed that Firmicutes, Bacteroidetes and Verrucomicrobia dominated mouse gut bacterial communities. Rag1(-) mice had a distinct microbiota that was phylogenetically different from wild-type mice. In particular, the bacterium Akkermansia muciniphila was highly enriched in Rag1(-/-) mice compared with the wild type. This enrichment was suppressed when Rag1(-/-) mice received bone marrows from wild-type mice. The microbial community diversity increased with age, albeit the magnitude depended on Rag1 status. In addition, Rag1(-/-) mice had a higher gain in microbiota richness and evenness with increase in age compared with wild-type mice, possibly due to the lack of pressure from the adaptive immune system. Our results suggest that adaptive immunity has a pervasive role in regulating gut microbiota's composition and diversity. PMID:25216087

  3. Childhood obesity: a role for gut microbiota?

    PubMed

    Sanchez, Marina; Panahi, Shirin; Tremblay, Angelo

    2015-01-01

    Obesity is a serious public health issue affecting both children and adults. Prevention and management of obesity is proposed to begin in childhood when environmental factors exert a long-term effect on the risk for obesity in adulthood. Thus, identifying modifiable factors may help to reduce this risk. Recent evidence suggests that gut microbiota is involved in the control of body weight, energy homeostasis and inflammation and thus, plays a role in the pathophysiology of obesity. Prebiotics and probiotics are of interest because they have been shown to alter the composition of gut microbiota and to affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community. As shown in this review, prebiotics and probiotics have physiologic functions that contribute to changes in the composition of gut microbiota, maintenance of a healthy body weight and control of factors associated with childhood obesity through their effects on mechanisms controlling food intake, fat storage and alterations in gut microbiota. PMID:25546278

  4. Assessment of the hormonal milieu.

    PubMed

    Hankinson, Susan E; Tworoger, Shelley S

    2011-01-01

    The hormonal milieu has been hypothesized to play a role in a range of human diseases, and therefore has been a topic of much epidemiologic investigation. Hormones of particular interest include: sex steroids; growth hormones; insulin-like growth factors; stress hormones, such as cortisol; and hormones produced by the adipose tissue, termed adipokines. Depending on the hormone, levels may be measured in plasma or serum, urine, saliva, tissue, or by assessing genetic variation in the hormone or hormone metabolizing genes. Sample collection, processing, and storage requirements vary according to the type of sample collected (e.g. blood or urine) and the hormone of interest. Laboratory analysis of hormones is frequently complex, and the technology used to conduct the assays is constantly evolving. For example, direct or indirect radioimmunoassay, bioassay or mass spectrometry can be used to measure sex steroids, each having advantages and disadvantages. Careful attention to laboratory issues, including close collaboration with laboratory colleagues and ongoing quality control assessments, is critical. Whether a single hormone measurement, as is frequently collected in epidemiologic studies, is sufficient to characterize the hormonal environment of interest (e.g. long-term adult hormone exposure) is also an important issue. While the assessment of hormones in epidemiologic studies is complex, these efforts have, and will continue to, add importantly to our knowledge of the role of hormones in human health. PMID:22997864

  5. The use of non-insulin anti-diabetic agents to improve glycemia without hypoglycemia in the hospital setting: focus on incretins.

    PubMed

    Schwartz, Stanley; DeFronzo, Ralph A

    2014-03-01

    Patients with hyperglycemia in hospital have increased adverse outcomes compared with patients with normoglycemia, and the pathophysiological causes seem relatively well understood. Thus, a rationale for excellent glycemic control exists. Benefits of control with intensive insulin regimes are highly likely based on multiple published studies. However, hypoglycemia frequency increases and adverse outcomes of hypoglycemia accrue. This has resulted in a 'push' for therapeutic nihilism, accepting higher glycemic levels to avoid hypoglycemia. One would ideally prefer to optimize glycemia, treating hyperglycemia while minimizing or avoiding hypoglycemia. Thus, one would welcome therapies and processes of care to optimize this benefit/ risk ratio. We review the logic and early studies that suggest that incretin therapy use in-hospital can achieve this ideal. We strongly urge randomized prospective controlled studies to test our proposal and we offer a process of care to facilitate this research and their use in our hospitalized patients. PMID:24515252

  6. Diminution of the gut resistome after a gut microbiota-targeted dietary intervention in obese children

    PubMed Central

    Wu, Guojun; Zhang, Chenhong; Wang, Jing; Zhang, Feng; Wang, Ruirui; Shen, Jian; Wang, Linghua; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping; Zhang, Menghui

    2016-01-01

    The gut microbiome represents an important reservoir of antibiotic resistance genes (ARGs). Effective methods are urgently needed for managing the gut resistome to fight against the antibiotic resistance threat. In this study, we show that a gut microbiota-targeted dietary intervention, which shifts the dominant fermentation of gut bacteria from protein to carbohydrate, significantly diminished the gut resistome and alleviated metabolic syndrome in obese children. Of the non-redundant metagenomic gene catalog of ~2 × 106 microbial genes, 399 ARGs were identified in 131 gene types and conferred resistance to 47 antibiotics. Both the richness and diversity of the gut resistome were significantly reduced after the intervention. A total of 201 of the 399 ARGs were carried in 120 co-abundance gene groups (CAGs) directly binned from the gene catalog across both pre-and post-intervention samples. The intervention significantly reduced several CAGs in Klebsiella, Enterobacter and Escherichia, which were the major hubs for multiple resistance gene types. Thus, dietary intervention may become a potentially effective method for diminishing the gut resistome. PMID:27044409

  7. It's a gut feeling: How the gut microbiota affects the state of mind

    PubMed Central

    Farmer, Adam D; Randall, Holly A; Aziz, Qasim

    2014-01-01

    Common human experience shows that stress and anxiety may modulate gut function. Such observations have been combined with an increasing evidence base that has culminated in the concept of the brain–gut axis. Nevertheless, it has not been until recently that the gut and its attendant components have been considered to influence higher cerebral function and behaviour per se. Moreover, the proposal that the gut and the bacteria contained therein (collectively referred to as the microbiota) can modulate mood and behaviours, has an increasing body of supporting evidence, albeit largely derived from animal studies. The gut microbiota is a dynamic and diverse ecosystem and forms a symbiotic relationship with the host. Herein we describe the components of the gut microbiota and mechanisms by which it can influence neural development, complex behaviours and nociception. Furthermore, we propose the novel concept of a ‘state of gut’ rather than a state of mind, particularly in relation to functional bowel disorders. Finally, we address the exciting possibility that the gut microbiota may offer a novel area of therapeutic intervention across a diverse array of both affective and gastrointestinal disorders. PMID:24665099

  8. Gut Bacteria May Hold Clues to Chronic Fatigue Syndrome

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159905.html Gut Bacteria May Hold Clues to Chronic Fatigue Syndrome Intestinal ... doctors -- may be influenced by a person's intestinal bacteria -- sometimes called gut microbiome, new research finds. "Patients ...

  9. Emerging Concepts on the Gut Microbiome and Multiple Sclerosis.

    PubMed

    Glenn, Justin D; Mowry, Ellen M

    2016-06-01

    Microbiota of the human body perform fundamental tasks that contribute to normal development, health, and homeostasis and are intimately associated with numerous organ systems, including the gut. Microbes begin gut inhabitance immediately following birth and promote proper gut epithelial construction and function, metabolism and nutrition, and immune system development. Inappropriate immune recognition of self-tissue can lead to autoimmune disease, including conditions such as multiple sclerosis (MS), in which the immune system recognizes and attacks central nervous system tissue. Preclinical studies have demonstrated a requirement of gut microbiota for neuroinflammatory autoimmune disease in animal models, and a growing number of clinical investigations are finding associations between MS status and the composition of the gut microbiota. In this review, we examine current undertakings into better understanding the role of gut bacteria and their phages in MS development, review associations of the gut microbiota makeup and MS, and discuss potential mechanisms by which the gut microbiota may be manipulated for therapeutic benefit. PMID:27145057

  10. Long-term pancreatic duct occlusion impairs the entero-insular axis in the dog--failure of plasma VIP to respond as "incretin".

    PubMed

    Schwille, P O; Engelhardt, W; Gumbert, E; Gebhardt, C; Gall, F P

    1984-01-01

    The response of VIP to either an oral glucose load (OGT) or intravenous glucose (IV glucose), aimed at reproducing the plasma glucose level after OGT, was studied in trained, conscious, sham-operated (Sham; n = 6) dogs, and dogs having initially (12 months before the glucose experiments) undergone occlusion of the pancreatic duct by the prolamine glue technique (Occ; n = 5). As a result, prior to glucose studies, the exocrine pancreas function was found subtotally reduced, as indirectly evaluated by the para-aminobenzoic acid (PABA) test, but no signs of diabetes were detected. The two studies with glucose administration designed to demonstrate the release of insulin, VIP, somatostatin into plasma as modified by enteric signals (represented by the difference of plasma peptide concentration during OGT minus peptide concentration during IV glucose) revealed the following: (1) basal plasma glucose, insulin, VIP, somatostatin did not differ between Sham and Occ dogs; (2) after OGT in Occ dogs the plasma glucose was elevated, whereas plasma insulin was markedly reduced, and VIP, somatostatin were largely unchanged; (3) the integrated output of insulin only was impaired when considering the so-called entero-insulin axis, while integrated VIP, somatostatin were unaltered. It was concluded (a) the Occ procedure in the dog has the capacity to subtotal destruction of the pancreatic acinar tissue, and of the entero-insular axis of insulin, the latter through yet unknown pathways, (b) the Occ technique may be a useful tool for investigation of the nature of "incretin," (c) VIP and somatostatin do not respond to elevated blood glucose and may have no role in the "incretin" concept of enteric modulation of the B-cell. PMID:6147819

  11. The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics

    PubMed Central

    Ridlon, Jason M.; Bajaj, Jasmohan S.

    2015-01-01

    The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an “endocrine organ” with potential to alter host physiology, perhaps to their own favor. We propose the term “sterolbiome” to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed. PMID:26579434

  12. The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics.

    PubMed

    Ridlon, Jason M; Bajaj, Jasmohan S

    2015-03-01

    The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an "endocrine organ" with potential to alter host physiology, perhaps to their own favor. We propose the term "sterolbiome" to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed. PMID:26579434

  13. Human genetics shape the gut microbiome

    PubMed Central

    Goodrich, Julia K.; Waters, Jillian L.; Poole, Angela C.; Sutter, Jessica L.; Koren, Omry; Blekhman, Ran; Beaumont, Michelle; Van Treuren, William; Knight, Rob; Bell, Jordana T.; Spector, Timothy D.; Clark, Andrew G.; Ley, Ruth E.

    2014-01-01

    Summary Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across > 1,000 fecal samples obtained from the TwinsUK population, including 416 twin-pairs. We identified many microbial taxa whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a cooccurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a cultured member of the Christensenellaceae, and transplanted to germfree mice. C. minuta amendment reduced weight gain and altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human gut microbiome and can do so in ways that impact host metabolism. PMID:25417156

  14. Rapamycin preserves gut homeostasis during Drosophila aging.

    PubMed

    Fan, Xiaolan; Liang, Qing; Lian, Ting; Wu, Qi; Gaur, Uma; Li, Diyan; Yang, Deying; Mao, Xueping; Jin, Zhihua; Li, Ying; Yang, Mingyao

    2015-11-01

    Gut homeostasis plays an important role in maintaining the overall body health during aging. Rapamycin, a specific inhibitor of mTOR, exerts prolongevity effects in evolutionarily diverse species. However, its impact on the intestinal homeostasis remains poorly understood. Here, we demonstrate that rapamycin can slow down the proliferation rate of intestinal stem cells (ISCs) in the aging guts and induce autophagy in the intestinal epithelium in Drosophila. Rapamycin can also significantly affect the FOXO associated genes in intestine and up-regulate the negative regulators of IMD/Rel pathway, consequently delaying the microbial expansion in the aging guts. Collectively, these findings reveal that rapamycin can delay the intestinal aging by inhibiting mTOR and thus keeping stem cell proliferation in check. These results will further explain the mechanism of healthspan and lifespan extension by rapamycin in Drosophila. PMID:26431326

  15. Rapamycin preserves gut homeostasis during Drosophila aging

    PubMed Central

    Lian, Ting; Wu, Qi; Gaur, Uma; Li, Diyan; Yang, Deying; Mao, Xueping; Jin, Zhihua; Li, Ying; Yang, Mingyao

    2015-01-01

    Gut homeostasis plays an important role in maintaining the overall body health during aging. Rapamycin, a specific inhibitor of mTOR, exerts prolongevity effects in evolutionarily diverse species. However, its impact on the intestinal homeostasis remains poorly understood. Here, we demonstrate that rapamycin can slow down the proliferation rate of intestinal stem cells (ISCs) in the aging guts and induce autophagy in the intestinal epithelium in Drosophila. Rapamycin can also significantly affect the FOXO associated genes in intestine and up-regulate the negative regulators of IMD/Rel pathway, consequently delaying the microbial expansion in the aging guts. Collectively, these findings reveal that rapamycin can delay the intestinal aging by inhibiting mTOR and thus keeping stem cell proliferation in check. These results will further explain the mechanism of healthspan and lifespan extension by rapamycin in Drosophila. PMID:26431326

  16. Adenocarcinoma associated with tail gut cyst

    PubMed Central

    Wise, Susannah; Maloney-Patel, Nell; Rezac, Craig; Poplin, Elizabeth

    2013-01-01

    Primary adenocarcinomas of the presacral (retrorectal) space are rare. The diagnosis is usually delayed because of non-specific symptoms, and is made after a biopsy or surgery. These carcinomas arise from cystic lesions developing from remnants of the embryological postanal gut containing mucous-secreting epithelium, known as tail gut cysts. The potential for infection, perianal fistulas and most importantly, malignant change warrants an early complete surgical resection. From an oncologist’s perspective, the management of these carcinomas has varied, and has included adjuvant chemotherapy and/or radiation therapy. We describe here a rare case of adenocarcinoma associated with a tail gut cyst that was discovered incidentally and resected by a posterior approach (Kraske procedure). The patient has had clinical and periodic radiologic surveillance without any evidence of cancer recurrence for over a year and a half. PMID:23450681

  17. Metabolic tinkering by the gut microbiome

    PubMed Central

    Selkrig, Joel; Wong, Peiyan; Zhang, Xiaodong; Pettersson, Sven

    2014-01-01

    Brain development is an energy demanding process that relies heavily upon diet derived nutrients. Gut microbiota enhance the host’s ability to extract otherwise inaccessible energy from the diet via fermentation of complex oligosaccharides in the colon. This nutrient yield is estimated to contribute up to 10% of the host’s daily caloric requirement in humans and fluctuates in response to environmental variations. Research over the past decade has demonstrated a surprising role for the gut microbiome in normal brain development and function. In this review we postulate that perturbations in the gut microbial-derived nutrient supply, driven by environmental variation, profoundly impacts upon normal brain development and function. PMID:24685620

  18. Prebiotics as gut microflora management tools.

    PubMed

    Gibson, Glenn R

    2008-07-01

    Functional foods is an often-used term applied to dietary ingredients that serve to improve consumer health. Over the last few decades, these foods have gained in popularity with sales continuing to increase rapidly. Recent scientific, and some lay, reports have shown the popularity of both probiotics and prebiotics. These serve to elicit changes in the gut microbiota composition that increase populations of purported beneficial gut bacterial genera, for example, lactobacilli or bifidobacteria. Probiotics use live microbial feed additions, whereas prebiotics target indigenous flora components. As gastrointestinal disorders are prevalent in terms of human health, both probiotics and prebiotics serve an important role in the prophylactic management of various acute and chronic gut derived conditions. Examples include protection from gastroenteritis and some inflammatory conditions. PMID:18542038

  19. Gut Microbiome and Kidney Disease in Pediatrics: Does Connection Exist?

    PubMed Central

    Vasylyeva, Tetyana L.; Singh, Ruchi

    2016-01-01

    Child development is a unique and continuous process that is impacted by genetics and environmental factors. Gut microbiome changes with development and depends on the stage of gut maturation, nutrition, and overall health. In spite of emerging data and active study in adults, the gut-renal axis in pediatrics has not been well considered and investigated. This review will focus on the current knowledge of gut microbiota impacts on kidney disease with extrapolation to the pediatric population. PMID:26973613

  20. Thyroid hormone resistance.

    PubMed

    Olateju, Tolulope O; Vanderpump, Mark P J

    2006-11-01

    Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited syndrome of reduced end-organ responsiveness to thyroid hormone. Patients with RTH have elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations and normal or slightly elevated serum thyroid stimulating hormone (TSH) level. Despite a variable clinical presentation, the common characteristic clinical features are goitre but an absence of the usual symptoms and metabolic consequences of thyroid hormone excess. Patients with RTH can be classified on clinical grounds alone into either generalized resistance (GRTH), pituitary resistance (PRTH) or combined. Mutations in the thyroid hormone receptor (TR) beta gene are responsible for RTH and 122 different mutations have now been identified belonging to 300 families. With the exception of one family found to have complete deletion of the TRbeta gene, all others have been demonstrated to have minor alterations at the DNA level. The differential diagnosis includes a TSH-secreting pituitary adenoma and the presence of endogenous antibodies directed against thyroxine (T4) and triiodothyronine (T3). Failure to differentiate RTH from primary thyrotoxicosis has resulted in the inappropriate treatment of nearly one-third of patients. Although occasionally desirable, no specific treatment is available for RTH; however, the diagnosis allows appropriate genetic counselling. PMID:17132274

  1. Plant peptide hormone signalling.

    PubMed

    Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

    2015-01-01

    The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. PMID:26374891

  2. [Hormones and hair growth].

    PubMed

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair. PMID:20502852

  3. Gut inflammation in chronic fatigue syndrome.

    PubMed

    Lakhan, Shaheen E; Kirchgessner, Annette

    2010-01-01

    Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis.Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut.If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients. PMID:20939923

  4. Insights from characterizing extinct human gut microbiomes.

    PubMed

    Tito, Raul Y; Knights, Dan; Metcalf, Jessica; Obregon-Tito, Alexandra J; Cleeland, Lauren; Najar, Fares; Roe, Bruce; Reinhard, Karl; Sobolik, Kristin; Belknap, Samuel; Foster, Morris; Spicer, Paul; Knight, Rob; Lewis, Cecil M

    2012-01-01

    In an effort to better understand the ancestral state of the human distal gut microbiome, we examine feces retrieved from archaeological contexts (coprolites). To accomplish this, we pyrosequenced the 16S rDNA V3 region from duplicate coprolite samples recovered from three archaeological sites, each representing a different depositional environment: Hinds Cave (~8000 years B.P.) in the southern United States, Caserones (1600 years B.P.) in northern Chile, and Rio Zape in northern Mexico (1400 years B.P.). Clustering algorithms grouped samples from the same site. Phyletic representation was more similar within sites than between them. A Bayesian approach to source-tracking was used to compare the coprolite data to published data from known sources that include, soil, compost, human gut from rural African children, human gut, oral and skin from US cosmopolitan adults and non-human primate gut. The data from the Hinds Cave samples largely represented unknown sources. The Caserones samples, retrieved directly from natural mummies, matched compost in high proportion. A substantial and robust proportion of Rio Zape data was predicted to match the gut microbiome found in traditional rural communities, with more minor matches to other sources. One of the Rio Zape samples had taxonomic representation consistent with a child. To provide an idealized scenario for sample preservation, we also applied source tracking to previously published data for Ötzi the Iceman and a soldier frozen for 93 years on a glacier. Overall these studies reveal that human microbiome data has been preserved in some coprolites, and these preserved human microbiomes match more closely to those from the rural communities than to those from cosmopolitan communities. These results suggest that the modern cosmopolitan lifestyle resulted in a dramatic change to the human gut microbiome. PMID:23251439

  5. Insights from Characterizing Extinct Human Gut Microbiomes

    PubMed Central

    Tito, Raul Y.; Knights, Dan; Metcalf, Jessica; Obregon-Tito, Alexandra J.; Cleeland, Lauren; Najar, Fares; Roe, Bruce; Reinhard, Karl; Sobolik, Kristin; Belknap, Samuel; Foster, Morris; Spicer, Paul; Knight, Rob; Lewis, Cecil M.

    2012-01-01

    In an effort to better understand the ancestral state of the human distal gut microbiome, we examine feces retrieved from archaeological contexts (coprolites). To accomplish this, we pyrosequenced the 16S rDNA V3 region from duplicate coprolite samples recovered from three archaeological sites, each representing a different depositional environment: Hinds Cave (∼8000 years B.P.) in the southern United States, Caserones (1600 years B.P.) in northern Chile, and Rio Zape in northern Mexico (1400 years B.P.). Clustering algorithms grouped samples from the same site. Phyletic representation was more similar within sites than between them. A Bayesian approach to source-tracking was used to compare the coprolite data to published data from known sources that include, soil, compost, human gut from rural African children, human gut, oral and skin from US cosmopolitan adults and non-human primate gut. The data from the Hinds Cave samples largely represented unknown sources. The Caserones samples, retrieved directly from natural mummies, matched compost in high proportion. A substantial and robust proportion of Rio Zape data was predicted to match the gut microbiome found in traditional rural communities, with more minor matches to other sources. One of the Rio Zape samples had taxonomic representation consistent with a child. To provide an idealized scenario for sample preservation, we also applied source tracking to previously published data for Ötzi the Iceman and a soldier frozen for 93 years on a glacier. Overall these studies reveal that human microbiome data has been preserved in some coprolites, and these preserved human microbiomes match more closely to those from the rural communities than to those from cosmopolitan communities. These results suggest that the modern cosmopolitan lifestyle resulted in a dramatic change to the human gut microbiome. PMID:23251439

  6. Cosmology of F-theory GUTs

    NASA Astrophysics Data System (ADS)

    Heckman, Jonathan J.; Tavanfar, Alireza; Vafa, Cumrun

    2010-04-01

    In this paper we study the interplay between the recently proposed F-theory GUTs and cosmology. Despite the fact that the parameter range for F-theory GUT models is very narrow, we find that F-theory GUTs beautifully satisfy most cosmological constraints without any further restrictions. The viability of the scenario hinges on the interplay between various components of the axion supermultiplet, which in F-theory GUTs is also responsible for breaking supersymmetry. In these models, the gravitino is the LSP and develops a mass by eating the axino mode. The radial component of the axion supermultiplet known as the saxion typically begins to oscillate in the early Universe, eventually coming to dominate the energy density. Its decay reheats the Universe to a temperature of ˜1GeV, igniting BBN and diluting all thermal relics such as the gravitino by a factor of ˜10-4 - 10-5 such that gravitinos contribute a sizable component of the dark matter. In certain cases, non-thermally produced relics such as the axion, or gravitinos generated from the decay of the saxion can also contribute to the abundance of dark matter. Remarkably enough, this cosmological scenario turns out to be independent of the initial reheating temperature of the Universe. This is due to the fact that the initial oscillation temperature of the saxion coincides with the freeze out temperature for gravitinos in F-theory GUTs. We also find that saxion dilution is compatible with generating the desired baryon asymmetry from standard leptogenesis. Finally, the gravitino mass range in F-theory GUTs is 10 - 100MeV, which interestingly coincides with the window of values required for the decay of the NLSP to solve the problem of 7 Li over-production.

  7. Gastrointestinal Hormones and Bariatric Surgery-induced Weight Loss

    PubMed Central

    Ionut, Viorica; Burch, Miguel; Youdim, Adrienne; Bergman, Richard N.

    2015-01-01

    Obesity continues to be a major public health problem in the United States and worldwide. While recent statistics have demonstrated that obesity rates have begun to plateau, more severe classes of obesity are accelerating at a faster pace with important implications in regards to treatment. Bariatric surgery has a profound and durable effect on weight loss, being to date one of the most successful interventions for obesity. Objective To provide updates to the possible role of gut hormones in post bariatric surgery weight loss and weight loss maintenance. Design and Methods The current review examines the changes in gastro-intestinal hormones with bariatric surgery and the potential mechanisms by which these changes could result in decreased weight and adiposity. Results The mechanism by which bariatric surgery results in body weight changes is incompletely elucidated, but it clearly goes beyond caloric restriction and malabsorption. Conclusion Changes in gastro-intestinal hormones, including increases in GLP-1, PYY, and oxyntomodulin, decreases in GIP and ghrelin, or the combined action of all these hormones might play a role in induction and long-term maintenance of weight loss. PMID:23512841

  8. What is Obesity Doing to Your Gut?

    PubMed

    Lee, Yeong Yeh

    2015-01-01

    Obesity is a fast-emerging epidemic in the Asia-Pacific region, with numbers paralleling the rising global prevalence within the past 30 years. The landscape of gut diseases in Asia has been drastically changed by obesity. In addition to more non-specific abdominal symptoms, obesity is the cause of gastro-oesophageal reflux disease, various gastrointestinal cancers (colorectal cancer, hepatocellular carcinoma, oesophageal adenocarcinoma, gastric cardia adenocarcinoma, pancreatic cancer and gallbladder cancer) and non-alcoholic fatty liver disease. Abnormal cross-talk between the gut microbiome and the obese host seems to play a central role in the pathogenesis, but more studies are needed. PMID:25892944

  9. Standard methods for research on apis mellifera gut symbionts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gut microbes can play an important role in digestion, disease resistance, and the general health of animals, but little is known about the biology of gut symbionts in Apis mellifera. This paper is part of a series on honey bee research methods, providing protocols for studying gut symbionts. We desc...

  10. Standard methods for research on Apis mellifera gut symbionts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gut microbes can play an important role in digestion, disease resistance, and the general health of animals, but little is known about the biology of gut symbionts in Apis mellifera. This paper is part of a series on honey bee research methods, providing protocols for studying gut symbionts. We desc...

  11. Functional roles of low calorie sweeteners on gut function.

    PubMed

    Meyer-Gerspach, A C; Wölnerhanssen, B; Beglinger, C

    2016-10-01

    This short review summarizes the effects of low calorie sweeteners (fructose, non-nutritive low calorie sweeteners) on gut functions focusing on the gut sweet taste receptor system. The effects of these molecules on secretion of gut peptides associated with glycemic homeostasis and appetite regulation is reviewed as well as effects on gastric emptying and glucose absorption. PMID:26861179

  12. The role of psychosocial factors in functional gut disease.

    PubMed

    Kamm, M A

    1998-01-01

    The link between psychological factors and functional gut disorders is indisputable. This review considers some of the mechanisms by which psychological state affect gut function, how these psychological factors and their effects on the gut might be measured, and how psychological treatments might benefit patients with functional disorders. PMID:10027671

  13. The role of serotonin in feeding and gut contractions in the honeybee☆

    PubMed Central

    French, Alice S.; Simcock, Kerry L.; Rolke, Daniel; Gartside, Sarah E.; Blenau, Wolfgang; Wright, Geraldine A.

    2014-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of feeding and digestion in many animals from worms to mammals. In insects, 5-HT functions both as a neurotransmitter and as a systemic hormone. Here we tested its role as a neurotransmitter in feeding and crop contractions and its role as a systemic hormone that affected feeding in adult foraging honeybees. We found 5-HT immunoreactive processes throughout the gut, including on the surface of the oesophagus, crop, proventriculus, and the midgut, as well as in the ventral nerve cord. mRNA transcripts for all four of the known bee 5-HT receptors (Am5-ht1A,2α,2β,7) were expressed in the crop and the midgut suggesting a functional role for 5-HT in these locations. Application of a cocktail of antagonists with activity against these known receptors to the entire gut in vivo reduced the rate of spontaneous contraction in the crop and proventriculus. Although feeding with sucrose caused a small elevation of endogenous 5-HT levels in the haemolymph, injection of exogenous 5-HT directly into the abdomen of the bee to elevate 5-HT in the haemolymph did not alter food intake. However, when 5-HT was injected into directly into the brain there was a reduction in intake of carbohydrate, amino acid, or toxin-laced food solutions. Our data demonstrate that 5-HT inhibits feeding in the brain and excites muscle contractions in the gut, but general elevation of 5-HT in the bee’s haemolymph does not affect food intake. PMID:24374107

  14. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach

    PubMed Central

    Pérez-Cobas, Ana Elena; Gosalbes, María José; Friedrichs, Anette; Knecht, Henrik; Artacho, Alejandro; Eismann, Kathleen; Otto, Wolfgang; Rojo, David; Bargiela, Rafael; von Bergen, Martin; Neulinger, Sven C; Däumer, Carolin; Heinsen, Femke-Anouska; Latorre, Amparo; Barbas, Coral; Seifert, Jana; dos Santos, Vitor Martins; Ott, Stephan J; Ferrer, Manuel; Moya, Andrés

    2013-01-01

    Objective Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy. Methods The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated. Results Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation. Conclusions This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and

  15. The gut microbiota and its correlations with the central nervous system disorders.

    PubMed

    Catanzaro, R; Anzalone, M; Calabrese, F; Milazzo, M; Capuana, M; Italia, A; Occhipinti, S; Marotta, F

    2015-09-01

    A mutual impact of gastrointestinal tract (GIT) and central nervous system (CNS) functions has been recognized since the mid-twentieth century. It is accepted that the so-called gut-brain axis provides a two-way homeostatic communication, through immunological, hormonal and neuronal signals. A dysfunction of this axis has been associated with the pathogenesis of some diseases both within and outside the GIT, that have shown an increase in incidence over the last decades. Studies comparing germ-free animals and animals exposed to pathogenic bacterial infections, probiotics or antibiotics suggest the participation of the microbiota in this communication and a role in host defense, regulation of immunity and autoimmune disease appearance. The GIT could represent a vulnerable area through which pathogens influence all aspects of physiology and even induce CNS neuro-inflammation. All those concepts may suggest the modulation of the gut microbiota as an achievable strategy for innovative therapies in complex disorders. Moving from this background, the present review discusses the relationship between intestinal microbiota and CNS and the effects in health and disease. We particularly look at how the commensal gut microbiota influences systemic immune response in some neurological disorders, highlighting its impact on pain and cognition in multiple sclerosis, Guillain-Barrè Syndrome, neurodevelopmental and behavioral disorders and Alzheimer's disease. In this review we discuss recent studies showing that the potential microbiota-gut-brain dialogue is implicated in neurodegenerative diseases. Gaining a better understanding of the relationship between microbiota and CNS could provide an insight on the pathogenesis and therapeutic strategies of these disorders. PMID:25390799

  16. Neural effects of gut- and brain-derived glucagon-like peptide-1 and its receptor agonist.

    PubMed

    Katsurada, Kenichi; Yada, Toshihiko

    2016-04-01

    Glucagon-like peptide-1 (GLP-1) is derived from both the enteroendocrine L cells and preproglucagon-expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP-1 is cleaved by dipeptidyl peptidase-4 yielding a half-life of less than 2 min, it is plausible that the gut-derived GLP-1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP-1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain-derived GLP-1 is restriction of feeding. GLP-1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP-1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase-4, and is highly likely to act on the brain by passing through the blood-brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP-1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP-1 and the pathway by which peripheral GLP-1 informs the brain, and then discuss recent findings on the central effects of GLP-1 and GLP-1 receptor agonists. PMID:27186358

  17. Gut Bacteria in Health and Disease

    PubMed Central

    2013-01-01

    A new era in medical science has dawned with the realization of the critical role of the “forgotten organ,” the gut micro-biota, in health and disease. Central to this beneficial interaction between the microbiota and host is the manner in which bacteria and most likely other microorganisms contained within the gut communicate with the host’s immune system and participate in a variety of metabolic processes of mutual benefit to the host and the microbe. The advent of high-throughput methodologies and the elaboration of sophisticated analytic systems have facilitated the detailed description of the composition of the microbial constituents of the human gut, as never before, and are now enabling comparisons to be made between health and various disease states. Although the latter approach is still in its infancy, some important insights have already been gained about how the microbiota might influence a number of disease processes both within and distant from the gut. These discoveries also lay the groundwork for the development of therapeutic strategies that might modify the microbiota (eg, through the use of probiot-ics). Although this area holds much promise, more high-quality trials of probiotics, prebiotics, and other microbiota-modifying approaches in digestive disorders are needed, as well as laboratory investigations of their mechanisms of action. PMID:24729765

  18. The Enigmatic Universe of the Herbivore Gut.

    PubMed

    Glass, N Louise

    2016-07-01

    The herbivore gut is a fascinating ecosystem exquisitely adapted to plant biomass degradation. Within this ecosystem, anaerobic fungi invade biomass and secrete hydrolytic enzymes. In a recent study, Solomon et al. characterized three anaerobic fungi by transcriptomics, proteomics, and functional analyses to identify novel components essential for plant biomass deconstruction. PMID:27257096

  19. The human gut virome: a multifaceted majority

    PubMed Central

    Ogilvie, Lesley A.; Jones, Brian V.

    2015-01-01

    Here, we outline our current understanding of the human gut virome, in particular the phage component of this ecosystem, highlighting progress, and challenges in viral discovery in this arena. We reveal how developments in high-throughput sequencing technologies and associated data analysis methodologies are helping to illuminate this abundant ‘biological dark matter.’ Current evidence suggests that the human gut virome is a highly individual but temporally stable collective, dominated by phages exhibiting a temperate lifestyle. This viral community also appears to encode a surprisingly rich functional repertoire that confers a range of attributes to their bacterial hosts, ranging from bacterial virulence and pathogenesis to maintaining host–microbiome stability and community resilience. Despite the significant advances in our understanding of the gut virome in recent years, it is clear that we remain in a period of discovery and revelation, as new methods and technologies begin to provide deeper understanding of the inherent ecological characteristics of this viral ecosystem. As our understanding increases, the nature of the multi-partite interactions occurring between host and microbiome will become clearer, helping us to more rationally define the concepts and principles that will underpin approaches to using human gut virome components for medical or biotechnological applications. PMID:26441861

  20. Diet, the Gut Microbiome, and Epigenetics

    PubMed Central

    Hullar, Meredith A. J.; Fu, Benjamin C.

    2014-01-01

    Increasingly, the gut microbiome is implicated in the etiology of cancer, not only as an infectious agent, but also by altering exposure to dietary compounds that influence disease risk. While the composition and metabolism of the gut microbiome is influenced by diet, the gut microbiome can also modify dietary exposures in ways that are beneficial or detrimental to the human host. The colonic bacteria metabolize macronutrients, either as specialists or in consortia of bacteria, in a variety of diverse metabolic pathways. Microbial metabolites of diet can also be epigenetic activators of gene expression that may influence cancer risk in humans. Epigenetic involves heritable changes in gene expression via post translational and post transcriptional modifications. Microbial metabolites can influence epigenetics by altering the pool of compounds used for modification or by directly inhibiting enzymes involved in epigenetic pathways. Colonic epithelium is immediately exposed to these metabolites, although some metabolites are also found in systemic circulation. In this review, we discuss the role of the gut microbiome in dietary metabolism and how microbial metabolites may influence gene expression linked to colon cancer risk. PMID:24855003

  1. Gut-liver axis: role of inflammasomes.

    PubMed

    Bawa, Manan; Saraswat, Vivek A

    2013-06-01

    Inflammasomes are large multiprotein complexes that have the ability to sense intracellular danger signals through special NOD-like receptors or NLRs. They include NLRP3, NLRC4, AIM2 and NLRP6. They are involved in recognizing diverse microbial (bacteria, viruses, fungi and parasites), stress and damage signals, which result in direct activation of caspase-1, leading to secretion of potent pro-inflammatory cytokines and pyroptosis. NLRP3 is the most studied antimicrobial immune response inflammasome. Recent studies reveal expression of inflammasomes in innate immune response cells including monocytes, macrophages, neutrophils, and dendritic cells. Inflammasome deficiency has been linked to alterations in the gastrointestinal microflora. Alterations in the microbiome population and/or changes in gut permeability promote microbial translocation into the portal circulation and thus directly to the liver. Gut derived lipopolysaccharides (LPS) play a significant role in several liver diseases. Recent advancements in the sequencing technologies along with improved methods in metagenomics and bioinformatics have provided effective tools for investigating the 10(14) microorganisms of the human microbiome that inhabit the human gut. In this review, we examine the significance of inflammasomes in relation to the gut microflora and liver. This review also highlights the emerging functions of human microbiota in health and liver diseases. PMID:25755488

  2. 'Gut health': a new objective in medicine?

    PubMed Central

    2011-01-01

    'Gut health' is a term increasingly used in the medical literature and by the food industry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. From a scientific point of view, however, it is still extremely unclear exactly what gut health is, how it can be defined and how it can be measured. The GI barrier adjacent to the GI microbiota appears to be the key to understanding the complex mechanisms that maintain gut health. Any impairment of the GI barrier can increase the risk of developing infectious, inflammatory and functional GI diseases, as well as extraintestinal diseases such as immune-mediated and metabolic disorders. Less clear, however, is whether GI discomfort in general can also be related to GI barrier functions. In any case, methods of assessing, improving and maintaining gut health-related GI functions are of major interest in preventive medicine. PMID:21401922

  3. Isolation of methanotrophic bacteria from termite gut.

    PubMed

    Reuss, Julia; Rachel, Reinhard; Kämpfer, Peter; Rabenstein, Andreas; Küver, Jan; Dröge, Stefan; König, Helmut

    2015-10-01

    The guts of termites feature suitable conditions for methane oxidizing bacteria (MOB) with their permanent production of CH4 and constant supply of O2 via tracheae. In this study, we have isolated MOB from the gut contents of the termites Incisitermes marginipennis, Mastotermes darwiniensis, and Neotermes castaneus for the first time. The existence of MOB was indicated by detecting pmoA, the gene for the particulate methane monooxygenase, in the DNA of gut contents. Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction supported those findings. The MOB cell titer was determined to be 10(2)-10(3) per gut. Analyses of the 16S rDNA from isolates indicated close similarity to the genus Methylocystis. After various physiological tests and fingerprinting methods, no exact match to a known species was obtained, indicating the isolation of new MOB species. However, MALDI-TOF MS analyses revealed a close relationship to Methylocystis bryophila and Methylocystis parvus. PMID:26411892

  4. Gut microbiota of Busseola fusca (Lepidoptera: Noctuidae).

    PubMed

    Snyman, Maxi; Gupta, Arvind Kumar; Bezuidenhout, Cornelius Carlos; Claassens, Sarina; van den Berg, Johnnie

    2016-07-01

    Busseola fusca (Fuller) (Lepidoptera: Noctuidae) is a stemborer pest that attacks maize (Zea mays) throughout sub-Saharan Africa. Genetically modified maize has been shown to be effective against B. fusca. However, resistance of B. fusca against Bt-maize has developed and spread throughout South Africa. Previous studies suggested that gut microbiota contribute to mortality across a range of Lepidoptera. To fully assess the role of microbiota within the gut, it is essential to understand the microbiota harboured by natural B. fusca populations. This study aimed to identify the gut-associated bacteria by 16S rRNA gene sequencing. A total of 78 bacterial strains were characterised from the midgut of B. fusca larvae that were collected from 30 sites across the maize producing region of South Africa. Molecular phylogenetic analyses revealed bacteria affiliated to Proteobacteria, Actinobacteria, and Firmicutes. Taxonomic distribution placed these isolates into 15 different genera representing 20 species. The majority of bacteria identified belong to the genera Bacillus, Enterococcus, and Klebsiella. The B. fusca gut represents an intriguing and unexplored niche for analysing microbial ecology. The study could provide opportunities for developing new targets for pest management and contribute to understanding the phenomenon of resistance evolution of this species. PMID:27263010

  5. Gut Microbiota and Lifestyle Interventions in NAFLD.

    PubMed

    Houghton, David; Stewart, Christopher J; Day, Christopher P; Trenell, Michael

    2016-01-01

    The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed "dysbiosis", has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gut microbiota to be linked with non-alcoholic fatty liver disease (NAFLD). Although the exact mechanism(s) remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gut microbiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise) affect the host-microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gut microbiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise) on gut microbiota and how this impacts upon NAFLD prognosis. PMID:27023533

  6. Gut ecosystem: how microbes help us.

    PubMed

    Martín, R; Miquel, S; Ulmer, J; Langella, P; Bermúdez-Humarán, L G

    2014-09-01

    The human gut houses one of the most complex and abundant ecosystems composed of up to 1013-1014 microorganisms. Although the anthropocentric concept of life has concealed the function of microorganisms inside us, the important role of gut bacterial community in human health is well recognised today. Moreover, different microorganims, which are commonly present in a large diversity of food products, transit through our gut every day adding in some cases a beneficial effect to our health (probiotics). This crosstalk is concentrated mainly in the intestinal epithelium, where microbes provide the host with essential nutrients and modulation of the immune system. Furthermore, microorganisms also display antimicrobial activities maintaining a gut ecosystem stable. This review summarises some of the recent findings on the interaction of both commensal and probiotic bacteria with each other and with the host. The aim is to highlight the cooperative status found in healthy individuals as well as the importance of this crosstalk in the maintenance of human homeostasis. PMID:24583612

  7. Nutritional protective mechanisms against gut inflammation☆

    PubMed Central

    Viladomiu, Monica; Hontecillas, Raquel; Yuan, Lijuan; Lu, Pinyi; Bassaganya-Riera, Josep

    2013-01-01

    Inflammatory bowel disease (IBD) is a debilitating and widespread immune-mediated illness characterized by excessive inflammatory and effector mucosal responses leading to tissue destruction at the gastrointestinal tract. Interactions among the immune system, the commensal microbiota and the host genotype are thought to underlie the pathogenesis of IBD. However, the precise etiology of IBD remains unknown. Diet-induced changes in the composition of the gut microbiome can modulate the induction of regulatory versus effector immune responses at the gut mucosa and improve health outcomes. Therefore, manipulation of gut microbiota composition and the local production of microbial-derived metabolites by using prebiotics, probiotics and dietary fibers is being explored as a promising avenue of prophylactic and therapeutic intervention against gut inflammation. Prebiotics and fiber carbohydrates are fermented by resident microflora into short chain fatty acids (SCFAs) in the colon. SCFAs then activate peroxisome proliferator-activated receptor (PPAR)γ, a nuclear transcription factor with widely demonstrated anti-inflammatory efficacy in experimental IBD. The activation of PPARγ by naturally ocurring compounds such as conjugated linoleic acid, pomegranate seed oil-derived punicic acid, eleostearic acid and abscisic acid has been explored as nutritional interventions that suppress colitis by directly modulating the host immune response. The aim of this review is to summarize the status of innovative nutritional interventions against gastrointestinal inflammation, their proposed mechanisms of action, preclinical and clinical efficacy as well as bioinformatics and computational modeling approaches that accelerate discovery in nutritional and mucosal immunology research. PMID:23541470

  8. The Gut Bacteria-Driven Obesity Development.

    PubMed

    Compare, Debora; Rocco, Alba; Sanduzzi Zamparelli, Marco; Nardone, Gerardo

    2016-01-01

    It is now well established that a healthy gut flora is largely responsible for the overall health of the host, while a perturbation in gut microbial communities can contribute to disease susceptibility. Obesity is a complex process involving genetic and environmental factors with an epidemiological burden that makes it a major public health issue. Studies of germ-free or gnotobiotic mice provided evidence that the diversity, as well as the presence and relative proportion of different microbes in the gut play active roles in energy homeostasis. Similarly, human studies showed that both the diversity of the microbiota and the Bacteroidetes/Firmicutes ratio are decreased in obese individuals. The 'obese microbiota' seems to be able to increase dietary energy harvest and favor weight gain and fat deposition. Although research in this field has just started and many of the available data are still conflicting, the results are providing exciting perspectives, and gut microbiota manipulation has already become a new target for both prevention and treatment of obesity. PMID:27028448

  9. Gut Microbiota and Allergic Disease. New Insights.

    PubMed

    Lynch, Susan V

    2016-03-01

    The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy. PMID:27027953

  10. Gut Microbiota and Lifestyle Interventions in NAFLD

    PubMed Central

    Houghton, David; Stewart, Christopher J.; Day, Christopher P.; Trenell, Michael

    2016-01-01

    The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed “dysbiosis”, has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gut microbiota to be linked with non-alcoholic fatty liver disease (NAFLD). Although the exact mechanism(s) remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gut microbiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise) affect the host–microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gut microbiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise) on gut microbiota and how this impacts upon NAFLD prognosis. PMID:27023533

  11. Prebiotics and gut microbiota in chickens.

    PubMed

    Pourabedin, Mohsen; Zhao, Xin

    2015-08-01

    Prebiotics are non-digestible feed ingredients that are metabolized by specific members of intestinal microbiota and provide health benefits for the host. Fermentable oligosaccharides are best known prebiotics that have received increasing attention in poultry production. They act through diverse mechanisms, such as providing nutrients, preventing pathogen adhesion to host cells, interacting with host immune systems and affecting gut morphological structure, all presumably through modulation of intestinal microbiota. Currently, fructooligosaccharides, inulin and mannanoligosaccharides have shown promising results while other prebiotic candidates such as xylooligosaccharides are still at an early development stage. Despite a growing body of evidence reporting health benefits of prebiotics in chickens, very limited studies have been conducted to directly link health improvements to prebiotic-dependent changes in the gut microbiota. This article visits the current knowledge of the chicken gastrointestinal microbiota and reviews most recent publications related to the roles played by prebiotics in modulation of the gut microbiota and immune functions. Progress in this field will help us better understand how the gut microbiota contributes to poultry health and productivity, and support the development of new prebiotic products as an alternative to in-feed antibiotics. PMID:26208530

  12. Redefining the gut as the motor of critical illness

    PubMed Central

    Mittal, Rohit; Coopersmith, Craig M.

    2013-01-01

    The gut is hypothesized to play a central role in the progression of sepsis and multiple organ dysfunction syndrome. Critical illness alters gut integrity by increasing epithelial apoptosis and permeability and by decreasing epithelial proliferation and mucus integrity. Additionally, toxic gut-derived lymph induces distant organ injury. Although the endogenous microflora ordinarily exist in a symbiotic relationship with the gut epithelium, severe physiologic insults alter this relationship, leading to induction of virulence factors in the microbiome, which, in turn, can perpetuate or worsen critical illness. This review highlights newly discovered ways in which the gut acts as the motor that perpetuates the systemic inflammatory response in critical illness. PMID:24055446

  13. Redefining the gut as the motor of critical illness.

    PubMed

    Mittal, Rohit; Coopersmith, Craig M

    2014-04-01

    The gut is hypothesized to play a central role in the progression of sepsis and multiple organ dysfunction syndrome. Critical illness alters gut integrity by increasing epithelial apoptosis and permeability and by decreasing epithelial proliferation and mucus integrity. Additionally, toxic gut-derived lymph induces distant organ injury. Although the endogenous microflora ordinarily exist in a symbiotic relationship with the gut epithelium, severe physiological insults alter this relationship, leading to induction of virulence factors in the microbiome, which, in turn, can perpetuate or worsen critical illness. This review highlights newly discovered ways in which the gut acts as the motor that perpetuates the systemic inflammatory response in critical illness. PMID:24055446

  14. Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota.

    PubMed

    Bauer, Paige V; Hamr, Sophie C; Duca, Frank A

    2016-02-01

    Despite significant progress in understanding the homeostatic regulation of energy balance, successful therapeutic options for curbing obesity remain elusive. One potential target for the treatment of obesity is via manipulation of the gut-brain axis, a complex bidirectional communication system that is crucial in maintaining energy homeostasis. Indeed, ingested nutrients induce secretion of gut peptides that act either via paracrine signaling through vagal and non-vagal neuronal relays, or in an endocrine fashion via entry into circulation, to ultimately signal to the central nervous system where appropriate responses are generated. We review here the current hypotheses of nutrient sensing mechanisms of enteroendocrine cells, including the release of gut peptides, mainly cholecystokinin, glucagon-like peptide-1, and peptide YY, and subsequent gut-to-brain signaling pathways promoting a reduction of food intake and an increase in energy expenditure. Furthermore, this review highlights recent research suggesting this energy regulating gut-brain axis can be influenced by gut microbiota, potentially contributing to the development of obesity. PMID:26542800

  15. The Gut Epithelial Receptor LRRC19 Promotes the Recruitment of Immune Cells and Gut Inflammation.

    PubMed

    Cao, Shuisong; Su, Xiaomin; Zeng, Benhua; Yan, Hui; Huang, Yugang; Wang, Enlin; Yun, Huan; Zhang, Yuan; Liu, Feifei; Li, Wenxia; Wei, Hong; Che, Yongzhe; Yang, Rongcun

    2016-02-01

    Commensal microbes are necessary for a healthy gut immune system. However, the mechanism involving these microbes that establish and maintain gut immune responses is largely unknown. Here, we have found that the gut immune receptor leucine-rich repeat (LRR) C19 is involved in host-microbiota interactions. LRRC19 deficiency not only impairs the gut immune system but also reduces inflammatory responses in gut tissues. We demonstrate that the LRRC19-associated chemokines CCL6, CCL9, CXCL9, and CXCL10 play a critical role in immune cell recruitment and intestinal inflammation. The expression of these chemokines is associated with regenerating islet-derived (REG) protein-mediated microbiotas. We also found that the expression of REGs may be regulated by gut Lactobacillus through LRRC19-mediated activation of NF-κB. Therefore, our study establishes a regulatory axis of LRRC19, REGs, altered microbiotas, and chemokines for the recruitment of immune cells and the regulation of intestinal inflammation. PMID:26776522

  16. Role of DUOX in gut inflammation: lessons from Drosophila model of gut-microbiota interactions

    PubMed Central

    Kim, Sung-Hee; Lee, Won-Jae

    2013-01-01

    It is well-known that certain bacterial species can colonize the gut epithelium and induce inflammation in the mucosa, whereas other species are either benign or beneficial to the host. Deregulation of the gut-microbe interactions may lead to a pathogenic condition in the host, such as chronic inflammation, tissue injuries, and even cancer. However, our current understanding of the molecular mechanisms that underlie gut-microbe homeostasis and pathogenesis remains limited. Recent studies have used Drosophila as a genetic model to provide novel insights into the causes and consequences of bacterial-induced colitis in the intestinal mucosa. The present review discusses the interactions that occur between gut-associated bacteria and host gut immunity, particularly the bacterial-induced intestinal dual oxidase (DUOX) system. Several lines of evidence showed that the bacterial-modulated DUOX system is involved in microbial clearance, intestinal epithelial cell renewal (ECR), redox-dependent modulation of signaling pathways, cross-linking of biomolecules, and discrimination between symbionts and pathogens. Further genetic studies on the Drosophila DUOX system and on gut-associated bacteria with a distinct ability to activate DUOX may provide critical information related to the homeostatic inflammation as well as etiology of chronic inflammatory diseases, which will enhance our understanding on the mucosal inflammatory diseases frequently observed in the microbe-contacting epithelia of humans. PMID:24455491

  17. The Gut Epithelial Receptor LRRC19 Promotes the Recruitment of Immune Cells and Gut Inflammation

    PubMed Central

    Cao, Shuisong; Su, Xiaomin; Zeng, Benhua; Yan, Hui; Huang, Yugang; Wang, Enlin; Yun, Huan; Zhang, Yuan; Liu, Feifei; Li, Wenxia; Wei, Hong; Che, Yongzhe; Yang, Rongcun

    2016-01-01

    Summary Commensal microbes are necessary for a healthy gut immune system. However, the mechanism involving these microbes that establish and maintain gut immune responses is largely unknown. Here, we have found that the gut immune receptor leucine-rich repeat (LRR) C19 is involved in host-microbiota interactions. LRRC19 deficiency not only impairs the gut immune system but also reduces inflammatory responses in gut tissues. We demonstrate that the LRRC19-associated chemokines CCL6, CCL9, CXCL9, and CXCL10 play a critical role in immune cell recruitment and intestinal inflammation. The expression of these chemokines is associated with regenerating islet-derived (REG) protein-mediated microbiotas. We also found that the expression of REGs may be regulated by gut Lactobacillus through LRRC19-mediated activation of NF-κB. Therefore, our study establishes a regulatory axis of LRRC19, REGs, altered microbiotas, and chemokines for the recruitment of immune cells and the regulation of intestinal inflammation. PMID:26776522

  18. Hormone Therapy for Breast Cancer

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Hormone Therapy for Breast Cancer On This Page What are hormones? How do ... sensitive breast cancer: Adjuvant therapy for early-stage breast cancer : Research has shown that women treated for early- ...

  19. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  20. Side Effects of Hormone Therapy

    MedlinePlus

    ... Men Living with Prostate Cancer Side Effects of Hormone Therapy Side Effects Urinary Dysfunction Bowel Dysfunction Erectile Dysfunction Loss of Fertility Side Effects of Hormone Therapy Side Effects of Chemotherapy Side Effects: When ...

  1. Aging changes in hormone production

    MedlinePlus

    ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ... produce the same amount at a slower rate. AGING CHANGES The hypothalamus is located in the brain. ...

  2. GPR40 (FFAR1) – Combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo

    PubMed Central

    Hauge, Maria; Vestmar, Marie A.; Husted, Anna S.; Ekberg, Jeppe P.; Wright, Michael J.; Di Salvo, Jerry; Weinglass, Adam B.; Engelstoft, Maja S.; Madsen, Andreas N.; Lückmann, Michael; Miller, Michael W.; Trujillo, Maria E.; Frimurer, Thomas M.; Holst, Birgitte; Howard, Andrew D.; Schwartz, Thue W.

    2014-01-01

    Objectives GPR40 (FFAR1), a clinically proven anti-diabetes target, is a Gq-coupled receptor for long chain fatty acids (LCFA) stimulating insulin secretion directly and mediating a major part of the dietary triglyceride-induced secretion of the incretins GLP-1 and GIP. In phase-II studies the GPR40 agonist TAK-875 decreased blood glucose but surprisingly without stimulating incretins. Methods and results Here we find that GPR40 can signal through not only Gq and IP3 but also Gs and cAMP when stimulated with certain agonists such as AM-1638 and AM-5262 in contrast to the endogenous LCFA ligands and agonists such as TAK-875 and AM-837, which only signal through Gq. In competition binding against [3H]AM-1638 and [3H]L358 the Gq + Gs and the Gq-only agonists either competed for or showed positive cooperativity by increasing the binding of the two different radio-ligands, in opposite ways. Nevertheless, both the Gq-only and the Gq + Gs agonists all docked surprisingly well into the binding site for TAK-875 in the X-ray structure of GPR40. In murine intestinal primary cell-cultures the endogenous LCFAs and the Gq-only agonists stimulated GLP-1 secretion with rather poor efficacy as compared with the high efficacy Gq + Gs GPR40 agonists and a prototype GPR119 agonist. Similarly, in fasting both male and female mice the Gq + Gs agonists showed significantly higher efficacy than the Gq-only agonists in respect of increasing plasma GLP-1 and plasma GIP in a GPR40-dependent manner. Conclusions It is concluded that stimulation of GPR40 by endogenous LCFAs or by Gq-only synthetic agonists result in a rather limited incretin response, whereas Gq + Gs GPR40 agonists stimulate incretin secretion robustly. PMID:25685685

  3. The gut microbiota and its relationship to diet and obesity

    PubMed Central

    Clarke, Siobhan F.; Murphy, Eileen F.; Nilaweera, Kanishka; Ross, Paul R.; Shanahan, Fergus; O’Toole, Paul W.; Cotter, Paul D.

    2012-01-01

    Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain. PMID:22572830

  4. Gut Microbiota and Brain Function: An Evolving Field in Neuroscience.

    PubMed

    Foster, Jane A; Lyte, Mark; Meyer, Emeran; Cryan, John F

    2016-05-01

    There is a growing appreciation of the importance of gut microbiota to health and disease. This has been driven by advances in sequencing technology and recent findings demonstrating the important role of microbiota in common health disorders such as obesity. Moreover, the potential role of gut microbiota in influencing brain function, behavior, and mental health has attracted the attention of neuroscientists and psychiatrists. At the 29(th) International College of Neuropsychopharmacology (CINP) World Congress held in Vancouver, Canada, in June 2014, a group of experts presented the symposium, "Gut microbiota and brain function: Relevance to psychiatric disorders" to review the latest findings in how gut microbiota may play a role in brain function, behavior, and disease. The symposium covered a broad range of topics, including gut microbiota and neuroendocrine function, the influence of gut microbiota on behavior, probiotics as regulators of brain and behavior, and imaging the gut-brain axis in humans. This report provides an overview of these presentations. PMID:26438800

  5. Assessing the Human Gut Microbiota in Metabolic Diseases

    PubMed Central

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-01-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens–derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology. PMID:24065795

  6. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  7. [Hormonal contraception in autoimmpne diseases].

    PubMed

    Matyszkiewicz, Anna; Jach, Robert; Rajtar-Ciosek, Agnieszka; Basta, Tomasz

    2016-01-01

    The onset and the course of autoimmune diseases is influenced among other factors by the sex hormones. Hormonal contraception might affect the course of the autoimmune disease. The paper summarises the manner of save application of hormonal contraception in patients with autoimmune disease. PMID:27526427

  8. Reproductive hormones in the environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low detections of reproductive hormones, at the part per trillion concentrations, are frequently measured in surface and subsurface waters. These exogenous hormones are a concern because they can bind strongly to hormone receptors in animals and induce an endocrine response or disruption. Human heal...

  9. Bioidentical Hormones for Menopausal Hormone Therapy: Variation on a Theme

    PubMed Central

    Bythrow, Jenna

    2007-01-01

    BACKGROUND Progesterone creams and natural or bioidentical compounded estrogen preparations are being promoted to consumers as safe alternatives to conventional menopausal hormone therapy and as health-promoting tonics. No reliable data support these claims. SAFETY Natural hormones, including estradiol, estriol, estrone, and progesterone, can be expected to have the same adverse event profile as conventional menopausal hormone regimens. SALIVARY HORMONE TESTS Salivary tests may be used to persuade asymptomatic consumers to use hormones (or symptomatic patients to use higher doses than those needed to mitigate symptoms), a practice that can be expected to result in adverse events. PMID:17549577

  10. Cognitive Impairment by Antibiotic-Induced Gut Dysbiosis: Analysis of Gut Microbiota-Brain Communication

    PubMed Central

    Fröhlich, Esther E.; Farzi, Aitak; Mayerhofer, Raphaela; Reichmann, Florian; Jačan, Angela; Wagner, Bernhard; Zinser, Erwin; Bordag, Natalie; Magnes, Christoph; Fröhlich, Eleonore; Kashofer, Karl; Gorkiewicz, Gregor; Holzer, Peter

    2016-01-01

    Emerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. We hypothesized that the concerns related to antibiotic-induced gut dysbiosis can only adequately be addressed if the effect of intragastric treatment of adult mice with multiple antibiotics on (i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior is systematically investigated. Of the antibiotics used (ampicillin, bacitracin, meropenem, neomycin, vancomycin), ampicillin had some oral bioavailability but did not enter the brain. 16S rDNA sequencing confirmed antibiotic-induced microbial community disruption, and metabolomics revealed that gut dysbiosis was associated with depletion of bacteria-derived metabolites in the colon and alterations of lipid species and converted microbe-derived molecules in the plasma. Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis. PMID:26923630

  11. Cognitive impairment by antibiotic-induced gut dysbiosis: Analysis of gut microbiota-brain communication.

    PubMed

    Fröhlich, Esther E; Farzi, Aitak; Mayerhofer, Raphaela; Reichmann, Florian; Jačan, Angela; Wagner, Bernhard; Zinser, Erwin; Bordag, Natalie; Magnes, Christoph; Fröhlich, Eleonore; Kashofer, Karl; Gorkiewicz, Gregor; Holzer, Peter

    2016-08-01

    Emerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. We hypothesized that the concerns related to antibiotic-induced gut dysbiosis can only adequately be addressed if the effect of intragastric treatment of adult mice with multiple antibiotics on (i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior is systematically investigated. Of the antibiotics used (ampicillin, bacitracin, meropenem, neomycin, vancomycin), ampicillin had some oral bioavailability but did not enter the brain. 16S rDNA sequencing confirmed antibiotic-induced microbial community disruption, and metabolomics revealed that gut dysbiosis was associated with depletion of bacteria-derived metabolites in the colon and alterations of lipid species and converted microbe-derived molecules in the plasma. Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis. PMID:26923630

  12. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41

    PubMed Central

    Samuel, Buck S.; Shaito, Abdullah; Motoike, Toshiyuki; Rey, Federico E.; Backhed, Fredrik; Manchester, Jill K.; Hammer, Robert E.; Williams, S. Clay; Crowley, Jan; Yanagisawa, Masashi; Gordon, Jeffrey I.

    2008-01-01

    The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41−/− and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41−/− mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41−/− and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota. PMID:18931303

  13. Thyroid Hormone and Wound Healing

    PubMed Central

    Safer, Joshua D.

    2013-01-01

    Although thyroid hormone is one of the most potent stimulators of growth and metabolic rate, the potential to use thyroid hormone to treat cutaneous pathology has never been subject to rigorous investigation. A number of investigators have demonstrated intriguing therapeutic potential for topical thyroid hormone. Topical T3 has accelerated wound healing and hair growth in rodents. Topical T4 has been used to treat xerosis in humans. It is clear that the use of thyroid hormone to treat cutaneous pathology may be of large consequence and merits further study. This is a review of the literature regarding thyroid hormone action on skin along with skin manifestations of thyroid disease. The paper is intended to provide a context for recent findings of direct thyroid hormone action on cutaneous cells in vitro and in vivo which may portend the use of thyroid hormone to promote wound healing. PMID:23577275

  14. Regulation of Lactobacillus casei sorbitol utilization genes requires DNA-binding transcriptional activator GutR and the conserved protein GutM.

    PubMed

    Alcántara, Cristina; Sarmiento-Rubiano, Luz Adriana; Monedero, Vicente; Deutscher, Josef; Pérez-Martínez, Gaspar; Yebra, María J

    2008-09-01

    Sequence analysis of the five genes (gutRMCBA) downstream from the previously described sorbitol-6-phosphate dehydrogenase-encoding Lactobacillus casei gutF gene revealed that they constitute a sorbitol (glucitol) utilization operon. The gutRM genes encode putative regulators, while the gutCBA genes encode the EIIC, EIIBC, and EIIA proteins of a phosphoenolpyruvate-dependent sorbitol phosphotransferase system (PTS(Gut)). The gut operon is transcribed as a polycistronic gutFRMCBA messenger, the expression of which is induced by sorbitol and repressed by glucose. gutR encodes a transcriptional regulator with two PTS-regulated domains, a galactitol-specific EIIB-like domain (EIIB(Gat) domain) and a mannitol/fructose-specific EIIA-like domain (EIIA(Mtl) domain). Its inactivation abolished gut operon transcription and sorbitol uptake, indicating that it acts as a transcriptional activator. In contrast, cells carrying a gutB mutation expressed the gut operon constitutively, but they failed to transport sorbitol, indicating that EIIBC(Gut) negatively regulates GutR. A footprint analysis showed that GutR binds to a 35-bp sequence upstream from the gut promoter. A sequence comparison with the presumed promoter region of gut operons from various firmicutes revealed a GutR consensus motif that includes an inverted repeat. The regulation mechanism of the L. casei gut operon is therefore likely to be operative in other firmicutes. Finally, gutM codes for a conserved protein of unknown function present in all sequenced gut operons. A gutM mutant, the first constructed in a firmicute, showed drastically reduced gut operon expression and sorbitol uptake, indicating a regulatory role also for GutM. PMID:18676710

  15. Hormonal control of implantation.

    PubMed

    Sandra, Olivier

    2016-06-01

    In mammals, implantation represents a key step of pregnancy and its progression conditions not only the success of pregnancy but health of the offspring. Implantation requires a complex and specific uterine tissue, the endometrium, whose biological functions are tightly regulated by numerous signals, including steroids and polypeptide hormones. Endometrial tissue is endowed with dynamic properties that associate its ability to control the developmental trajectory of the embryo (driver property) and its ability to react to embryos displaying distinct capacities to develop to term (sensor property). Since dynamical properties of the endometrium can be affected by pre- and post-conceptional environment, determining how maternal hormonal signals and their biological actions are affected by environmental factors (e.g. nutrition, stress, infections) is mandatory to reduce or even to prevent their detrimental effects on endometrial physiology in order to preserve the optimal functionality of this tissue. PMID:27172870

  16. Hormones in pregnancy

    PubMed Central

    Kumar, Pratap; Magon, Navneet

    2012-01-01

    The endocrinology of human pregnancy involves endocrine and metabolic changes that result from physiological alterations at the boundary between mother and fetus. Progesterone and oestrogen have a great role along with other hormones. The controversies of use of progestogen and others are discussed in this chapter. Progesterone has been shown to stimulate the secretion of Th2 and reduces the secretion of Th1 cytokines which maintains pregnancy. Supportive care in early pregnancy is associated with a significant beneficial effect on pregnancy outcome. Prophylactic hormonal supplementation can be recommended for all assisted reproduction techniques cycles. Preterm labor can be prevented by the use of progestogen. The route of administration plays an important role in the drug's safety and efficacy profile in different trimesters of pregnancy. Thyroid disorders have a great impact on pregnancy outcome and needs to be monitored and treated accordingly. Method of locating review: Pubmed, scopus PMID:23661874

  17. The wound hormone jasmonate

    PubMed Central

    Koo, Abraham J.K.; Howe, Gregg A.

    2009-01-01

    Plant tissues are highly vulnerable to injury by herbivores, pathogens, mechanical stress, and other environmental insults. Optimal plant fitness in the face of these threats relies on complex signal transduction networks that link damage-associated signals to appropriate changes in metabolism, growth, and development. Many of these wound-induced adaptive responses are triggered by de novo synthesis of the plant hormone jasmonate (JA). Recent studies provide evidence that JA mediates systemic wound responses through distinct cell autonomous and nonautonomous pathways. In both pathways, bioactive JAs are recognized by an F-box protein-based receptor system that couples hormone binding to ubiquitin-dependent degradation of transcriptional repressor proteins. These results provide a new framework for understanding how plants recognize and respond to tissue injury. PMID:19695649

  18. The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

    PubMed

    West, Christina E; Renz, Harald; Jenmalm, Maria C; Kozyrskyj, Anita L; Allen, Katrina J; Vuillermin, Peter; Prescott, Susan L

    2015-01-01

    Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention. PMID:25567038

  19. Effects of microcystin-LR on gut microflora in different gut regions of mice.

    PubMed

    Chen, Jing; Xie, Ping; Lin, Juan; He, Jun; Zeng, Cheng; Chen, Jun

    2015-08-01

    To reveal the toxicological effects of the hepatotoxic microcystin-leucine arginine (MC-LR) on gut microbial community composition in different gut regions, we conducted a subchronic exposure of BALB/c mice to MC-LR via intragastric administration. Denaturing gradient gel electrophoresis (DGGE) was employed to profile the shifts of microbes after MC-LR treatment in the jejuno-ileum, caecum and colon. DGGE profiles analysis showed that MC-LR increased the microbial species richness (number of microbial bands) in the caecum and colon as well as microbial diversity (Shannon-Wiener index) in the caecum. The cluster analysis of DGGE profiles indicated that the microbial structures in the caecum and colon shifted significantly after MC-LR treatment, while that in the jejuno-ileum did not. All the relatively decreased gut microbes belonged to Clostridia in the Firmicutes phylum, and most of them were Lachnospiraceae. The increased ones derived from a variety of microbes including species from Porphyromonadaceae and Prevotellaceae in the Bacteroidetes phylum, as well as Lachnospiraceae and Ruminococcaceae in the Firmicutes phylum, and among which, the increase of Barnesiella in Porphyromonadaceae was most remarkable. In conclusion, subchronic exposure to MC-LR could disturb the balance of gut microbes in mice, and its toxicological effects varied between the jejuno-ileum and the other two gut regions. PMID:26165645

  20. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis.

    PubMed

    Stanisavljević, S; Lukić, J; Momčilović, M; Miljković, M; Jevtić, B; Kojić, M; Golić, N; Mostarica Stojković, M; Miljković, D

    2016-06-01

    Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis. PMID:26839070

  1. Gut Microbial Metabolites Fuel Host Antibody Responses.

    PubMed

    Kim, Myunghoo; Qie, Yaqing; Park, Jeongho; Kim, Chang H

    2016-08-10

    Antibody production is a metabolically demanding process that is regulated by gut microbiota, but the microbial products supporting B cell responses remain incompletely identified. We report that short-chain fatty acids (SCFAs), produced by gut microbiota as fermentation products of dietary fiber, support host antibody responses. In B cells, SCFAs increase acetyl-CoA and regulate metabolic sensors to increase oxidative phosphorylation, glycolysis, and fatty acid synthesis, which produce energy and building blocks supporting antibody production. In parallel, SCFAs control gene expression to express molecules necessary for plasma B cell differentiation. Mice with low SCFA production due to reduced dietary fiber consumption or microbial insufficiency are defective in homeostatic and pathogen-specific antibody responses, resulting in greater pathogen susceptibility. However, SCFA or dietary fiber intake restores this immune deficiency. This B cell-helping function of SCFAs is detected from the intestines to systemic tissues and conserved among mouse and human B cells, highlighting its importance. PMID:27476413

  2. Caspase deficiency alters the murine gut microbiome

    PubMed Central

    Brinkman, B M; Hildebrand, F; Kubica, M; Goosens, D; Del Favero, J; Declercq, W; Raes, J; Vandenabeele, P

    2011-01-01

    Caspases are aspartate-specific cysteine proteases that have an essential role in apoptosis and inflammation, and contribute to the maintenance of homeostasis in the intestine. These facts, together with the knowledge that caspases are implicated in host-microbe crosstalk, prompted us to investigate the effect of caspase (Casp)1, -3 and -7 deficiency on the composition of the murine gut microbiota. We observed significant changes in the abundance of the Firmicutes and Bacteroidetes phyla, in particular the Lachnospiraceae, Porphyromonodaceae and Prevotellacea families, when comparing Casp-1, -7 and -3 knockout mice with wild-type mice. Our data point toward an intricate relationship between these caspases and the composition of the murine gut microflora. PMID:22012254

  3. [Gut microbiota in health and disease].

    PubMed

    Icaza-Chávez, M E

    2013-01-01

    Gut microbiota is the community of live microorganisms residing in the digestive tract. There are many groups of researchers worldwide that are working at deciphering the collective genome of the human microbiota. Modern techniques for studying the microbiota have made us aware of an important number of nonculturable bacteria and of the relation between the microorganisms that live inside us and our homeostasis. The microbiota is essential for correct body growth, the development of immunity, and nutrition. Certain epidemics affecting humanity such as asthma and obesity may possibly be explained, at least partially, by alterations in the microbiota. Dysbiosis has been associated with a series of gastrointestinal disorders that include non-alcoholic fatty liver disease, celiac disease, and irritable bowel syndrome. The present article deals with the nomenclature, modern study techniques, and functions of gut microbiota, and its relation to health and disease. PMID:24290319

  4. Constraining SUSY GUTs and Inflation with Cosmology

    SciTech Connect

    Rocher, Jonathan

    2006-11-03

    In the framework of Supersymmetric Grand Unified Theories (SUSY GUTs), the universe undergoes a cascade of symmetry breakings, during which topological defects can be formed. We address the question of the probability of cosmic string formation after a phase of hybrid inflation within a large number of models of SUSY GUTs in agreement with particle and cosmological data. We show that cosmic strings are extremely generic and should be used to relate cosmology and high energy physics. This conclusion is employed together with the WMAP CMB data to strongly constrain SUSY hybrid inflation models. F-term and D-term inflation are studied in the SUSY and minimal SUGRA framework. They are both found to agree with data but suffer from fine tuning of their superpotential coupling ({lambda} (less-or-similar sign) 3 x 10-5 or less). Mass scales of inflation are also constrained to be less than M < or approx. 3 x 1015 GeV.

  5. Suppression of insulin production and secretion by a decretin hormone.

    PubMed

    Alfa, Ronald W; Park, Sangbin; Skelly, Kathleen-Rose; Poffenberger, Gregory; Jain, Nimit; Gu, Xueying; Kockel, Lutz; Wang, Jing; Liu, Yinghua; Powers, Alvin C; Kim, Seung K

    2015-02-01

    Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia, and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila ortholog of Neuromedin U receptors (NMURs), in insulin-producing cells phenocopied limostatin deficiency and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output. PMID:25651184

  6. Suppression of Insulin Production and Secretion by a Decretin Hormone

    PubMed Central

    Alfa, Ronald W.; Park, Sangbin; Skelly, Kathleen-Rose; Poffenberger, Gregory; Jain, Nimit; Gu, Xueying; Kockel, Lutz; Wang, Jing; Liu, Yinghua; Powers, Alvin C.; Kim, Seung K.

    2015-01-01

    SUMMARY Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila orthologue of Neuromedin U receptors (NMUR), in insulin-producing cells phenocopied limostatin deficiency, and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β-cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output. PMID:25651184

  7. Orbifold SUSY GUT from the Heterotic String

    SciTech Connect

    Kyae, Bumseok

    2008-11-23

    From the string partition function, we discuss the mass-shell and GSO projection conditions valid for Kaluza-Klein (KK) as well as massless states in the heterotic string theory compactifled on a nonprime orbifold. Using the obtained conditions we construct a 4D string standard model, which is embedded in a 6D SUSY GUT by including KK states above the compactiflcation scale. We discuss the stringy threshold corrections to gauge couplings, including the Wilson line effects.

  8. Caenorhabditis microbiota: worm guts get populated.

    PubMed

    Clark, Laura C; Hodgkin, Jonathan

    2016-01-01

    Until recently, almost nothing has been known about the natural microbiota of the model nematode Caenorhabditis elegans. Reporting their research in BMC Biology, Dirksen and colleagues describe the first sequencing effort to characterize the gut microbiota of environmentally isolated C. elegans and the related taxa Caenorhabditis briggsae and Caenorhabditis remanei In contrast to the monoxenic, microbiota-free cultures that are studied in hundreds of laboratories, it appears that natural populations of Caenorhabditis harbor distinct microbiotas. PMID:27160265

  9. Proton pump inhibitors affect the gut microbiome

    PubMed Central

    Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Tigchelaar, Ettje F; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

    2016-01-01

    Background and aims Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. Methods The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. Results 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10−38). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli. Conclusions The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs. PMID:26657899

  10. GUTs on Compact Type IIB Orientifolds

    SciTech Connect

    Blumenhagen, Ralph; Braun, Volker; Grimm, Thomas W.; Weigand, Timo; /SLAC

    2008-12-01

    We systematically analyze globally consistent SU(5) GUT models on intersecting D7-branes in genuine Calabi-Yau orientifolds with O3- and O7-planes. Beyond the well-known tadpole and K-theory cancellation conditions there exist a number of additional subtle but quite restrictive constraints. For the realization of SU(5) GUTs with gauge symmetry breaking via U(1)Y flux we present two classes of suitable Calabi-Yau manifolds defined via del Pezzo transitions of the elliptically fibred hypersurface P{sub 1,1,1,6,9}[18] and of the Quintic P{sub 1,1,1,1,1}[5], respectively. To define an orientifold projection we classify all involutions on del Pezzo surfaces. We work out the model building prospects of these geometries and present five globally consistent string GUT models in detail, including a 3-generation SU(5) model with no exotics whatsoever. We also realize other phenomenological features such as the 10 10 5{sub H} Yukawa coupling and comment on the possibility of moduli stabilization, where we find an entire new set of so-called swiss-cheese type Calabi-Yau manifolds. It is expected that both the general constrained structure and the concrete models lift to F-theory vacua on compact Calabi-Yau fourfolds.

  11. Gut microbiome and nonalcoholic fatty liver diseases.

    PubMed

    Zhu, Lixin; Baker, Robert D; Baker, Susan S

    2015-01-01

    We review recent findings and hypotheses on the roles of gut microbiome in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD). Microbial metabolites and cell components contribute to the development of hepatic steatosis and inflammation, key components of nonalcoholic steatohepatitis (NASH), the severe form of NAFLD. Altered gut microbiome can independently cause obesity, the most important risk factor for NAFLD. This capability is attributed to short-chain fatty acids (SCFAs), major gut microbial fermentation products. SCFAs account for a large portion of caloric intake of the host, and they enhance intestinal absorption by activating GLP-2 signaling. However, elevated SCFAs may be an adaptive measure to suppress colitis, which could be a higher priority than imbalanced calorie intake. The microbiome of NASH patients features an elevated capacity for alcohol production. The pathomechanisms for alcoholic steatohepatitis may apply to NASH. NAFLD/NASH is associated with elevated Gram-negative microbiome and endotoxemia. However, many NASH patients exhibited normal serum endotoxin indicating that endotoxemia is not required for the pathogenesis of NASH. These observations suggest that microbial intervention may benefit NAFLD/NASH patients. However, very limited effects were observed using traditional probiotic species. Novel probiotic therapy based on NAFLD/NASH specific microbial composition represents a promising future direction. PMID:25310763

  12. Gut feelings about the endocannabinoid system.

    PubMed

    Di Marzo, V; Piscitelli, F

    2011-05-01

    Stemming from the centuries-old and well known effects of Cannabis on intestinal motility and secretion, research on the role of the endocannabinoid system in gut function and dysfunction has received ever increasing attention since the discovery of the cannabinoid receptors and their endogenous ligands, the endocannabinoids. In this article, some of the most recent developments in this field are discussed, with particular emphasis on new data, most of which are published in Neurogastroenterology & Motility, on the potential tonic endocannabinoid control of intestinal motility, the function of cannabinoid type-1 (CB1) receptors in gastric function, visceral pain, inflammation and sepsis, the emerging role of cannabinoid type-2 (CB2) receptors in the gut, and the pharmacology of endocannabinoid-related molecules and plant cannabinoids not necessarily acting via cannabinoid CB1 and CB2 receptors. These novel data highlight the multi-faceted aspects of endocannabinoid function in the GI tract, support the feasibility of the future therapeutic exploitation of this signaling system for the treatment of GI disorders, and leave space for some intriguing new hypotheses on the role of endocannabinoids in the gut. PMID:21481098

  13. Gut microbiota imbalance and colorectal cancer

    PubMed Central

    Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde

    2016-01-01

    The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603

  14. Rapid evolution of the human gut virome.

    PubMed

    Minot, Samuel; Bryson, Alexandra; Chehoud, Christel; Wu, Gary D; Lewis, James D; Bushman, Frederic D

    2013-07-23

    Humans are colonized by immense populations of viruses, which metagenomic analysis shows are mostly unique to each individual. To investigate the origin and evolution of the human gut virome, we analyzed the viral community of one adult individual over 2.5 y by extremely deep metagenomic sequencing (56 billion bases of purified viral sequence from 24 longitudinal fecal samples). After assembly, 478 well-determined contigs could be identified, which are inferred to correspond mostly to previously unstudied bacteriophage genomes. Fully 80% of these types persisted throughout the duration of the 2.5-y study, indicating long-term global stability. Mechanisms of base substitution, rates of accumulation, and the amount of variation varied among viral types. Temperate phages showed relatively lower mutation rates, consistent with replication by accurate bacterial DNA polymerases in the integrated prophage state. In contrast, Microviridae, which are lytic bacteriophages with single-stranded circular DNA genomes, showed high substitution rates (>10(-5) per nucleotide each day), so that sequence divergence over the 2.5-y period studied approached values sufficient to distinguish new viral species. Longitudinal changes also were associated with diversity-generating retroelements and virus-encoded Clustered Regularly Interspaced Short Palindromic Repeats arrays. We infer that the extreme interpersonal diversity of human gut viruses derives from two sources, persistence of a small portion of the global virome within the gut of each individual and rapid evolution of some long-term virome members. PMID:23836644

  15. The Gut Microbiota of Wild Mice

    PubMed Central

    Weldon, Laura; Abolins, Stephen; Lenzi, Luca; Bourne, Christian; Riley, Eleanor M.; Viney, Mark

    2015-01-01

    The gut microbiota profoundly affects the biology of its host. The composition of the microbiota is dynamic and is affected by both host genetic and many environmental effects. The gut microbiota of laboratory mice has been studied extensively, which has uncovered many of the effects that the microbiota can have. This work has also shown that the environments of different research institutions can affect the mouse microbiota. There has been relatively limited study of the microbiota of wild mice, but this has shown that it typically differs from that of laboratory mice (and that maintaining wild caught mice in the laboratory can quite quickly alter the microbiota). There is also inter-individual variation in the microbiota of wild mice, with this principally explained by geographical location. In this study we have characterised the gut (both the caecum and rectum) microbiota of wild caught Mus musculus domesticus at three UK sites and have investigated how the microbiota varies depending on host location and host characteristics. We find that the microbiota of these mice are generally consistent with those described from other wild mice. The rectal and caecal microbiotas of individual mice are generally more similar to each other, than they are to the microbiota of other individuals. We found significant differences in the diversity of the microbiotas among mice from different sample sites. There were significant correlations of microbiota diversity and body weight, a measure of age, body-mass index, serum concentration of leptin, and virus, nematode and mite infection. PMID:26258484

  16. Impacts of gut bacteria on human health and diseases.

    PubMed

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  17. The microbiota-gut-brain axis in functional gastrointestinal disorders

    PubMed Central

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients’ quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other’s expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis. PMID:24921926

  18. Impacts of Gut Bacteria on Human Health and Diseases

    PubMed Central

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  19. Molecular Insight into Gut Microbiota and Rheumatoid Arthritis

    PubMed Central

    Wu, Xiaohao; He, Bing; Liu, Jin; Feng, Hui; Ma, Yinghui; Li, Defang; Guo, Baosheng; Liang, Chao; Dang, Lei; Wang, Luyao; Tian, Jing; Zhu, Hailong; Xiao, Lianbo; Lu, Cheng; Lu, Aiping; Zhang, Ge

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA. PMID:27011180

  20. The gut is the epicentre of antibiotic resistance

    PubMed Central

    2012-01-01

    The gut contains very large numbers of bacteria. Changes in the composition of the gut flora, due in particular to antibiotics, can happen silently, leading to the selection of highly resistant bacteria and Candida species. These resistant organisms may remain for months in the gut of the carrier without causing any symptoms or translocate through the gut epithelium, induce healthcare-associated infections, undergo cross-transmission to other individuals, and cause limited outbreaks. Techniques are available to prevent, detect, and treat the carriage of resistant organisms in the gut. However, evidence on these techniques is scant, the only exception being selective digestive decontamination (SDD), which has been extensively studied in neutropenic and ICU patients. After the destruction of resistant colonizing bacteria, which has been successfully obtained in several studies, the gut could be re-colonized with normal faecal flora or probiotics. Studies are warranted to evaluate this concept. PMID:23181506

  1. The multilayered innate immune defense of the gut.

    PubMed

    El Chamy, Laure; Matt, Nicolas; Ntwasa, Monde; Reichhart, Jean-Marc

    2015-01-01

    In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms. PMID:26068126

  2. The microbiota-gut-brain axis in functional gastrointestinal disorders.

    PubMed

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis. PMID:24921926

  3. Relative gut lengths of coral reef butterflyfishes (Pisces: Chaetodontidae)

    NASA Astrophysics Data System (ADS)

    Berumen, M. L.; Pratchett, M. S.; Goodman, B. A.

    2011-12-01

    Variation in gut length of closely related animals is known to generally be a good predictor of dietary habits. We examined gut length in 28 species of butterflyfishes (Chaetodontidae), which encompass a wide range of dietary types (planktivores, omnivores, and corallivores). We found general dietary patterns to be a good predictor of relative gut length, although we found high variation among groups and covariance with body size. The longest gut lengths are found in species that exclusively feed on the living tissue of corals, while the shortest gut length is found in a planktivorous species. Although we tried to control for phylogeny, corallivory has arisen multiple times in this family, confounding our analyses. The butterflyfishes, a speciose family with a wide range of dietary habits, may nonetheless provide an ideal system for future work studying gut physiology associated with specialization and foraging behaviors.

  4. Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia.

    PubMed

    Fukui, Hiroshi

    2015-03-27

    A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

  5. Gut solutions to a gut problem: bacteriocins, probiotics and bacteriophage for control of Clostridium difficile infection.

    PubMed

    Rea, Mary C; Alemayehu, Debebe; Ross, R Paul; Hill, Colin

    2013-09-01

    Clostridium difficile infection (CDI) is a major cause of morbidity and mortality among hospitalized patients and imposes a considerable financial burden on health service providers in both Europe and the USA. The incidence of CDI has dramatically increased in recent years, partly due to the emergence of a number of hypervirulent strains. The most commonly documented risk factors associated with CDIs are antibiotic usage leading to alterations of the gut microbiota, age >65 years and long-term hospital stay. Since standard therapies for antibiotic-associated diarrhoea and CDI have limited efficacy, there is now an urgent need for alternative therapeutics. In this review, we outline the current state of play with regard to the potential of gut-derived bacteriocins, probiotics and phage to act as antimicrobial agents against CDI in the human gut. PMID:23699066

  6. Gut Inflammation and Immunity: What Is the Role of the Human Gut Virome?

    PubMed Central

    Focà, Alfredo; Quirino, Angela; Marascio, Nadia; Zicca, Emilia; Pavia, Grazia

    2015-01-01

    The human virome comprises viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect other organisms, including bacteriophages and plant viruses. The development of high-throughput sequencing techniques has shown that the human gut microbiome is a complex community in which the virome plays a crucial role into regulation of intestinal immunity and homeostasis. Nevertheless, the size of the human virome is still poorly understood. Indeed the enteric virome is in a continuous and dynamic equilibrium with other components of the gut microbiome and the gut immune system, an interaction that may influence the health and disease of the host. We review recent evidence on the viruses found in the gastrointestinal tract, discussing their interactions with the resident bacterial microbiota and the host immune system, in order to explore the potential impact of the virome on human health. PMID:25944980

  7. A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson's disease by reducing chronic inflammation in the brain.

    PubMed

    Cao, Lijun; Li, Dongfang; Feng, Peng; Li, Lin; Xue, Guo-Fang; Li, Guanglai; Hölscher, Christian

    2016-04-13

    The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD. PMID:26918675

  8. Gut Microbiota as Potential Orchestrators of Irritable Bowel Syndrome

    PubMed Central

    Bennet, Sean M.P.; Öhman, Lena; Simrén, Magnus

    2015-01-01

    Irritable bowel syndrome (IBS) is a multifactorial functional disorder with no clearly defined etiology or pathophysiology. Modern culture-independent techniques have improved the understanding of the gut microbiota’s composition and demonstrated that an altered gut microbiota profile might be found in at least some subgroups of IBS patients. Research on IBS from a microbial perspective is gaining momentum and advancing. This review will therefore highlight potential links between the gut microbiota and IBS by discussing the current knowledge of the gut microbiota; it will also illustrate bacterial-host interactions and how alterations to these interactions could exacerbate, induce or even help alleviate IBS. PMID:25918261

  9. Brain Gut Microbiome Interactions and Functional Bowel Disorders

    PubMed Central

    Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

    2014-01-01

    Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

  10. Gut microbiota as potential orchestrators of irritable bowel syndrome.

    PubMed

    Bennet, Sean M P; Ohman, Lena; Simren, Magnus

    2015-05-23

    Irritable bowel syndrome (IBS) is a multifactorial functional disorder with no clearly defined etiology or pathophysiology. Modern culture-independent techniques have improved the understanding of the gut microbiota's composition and demonstrated that an altered gut microbiota profile might be found in at least some subgroups of IBS patients. Research on IBS from a microbial perspective is gaining momentum and advancing. This review will therefore highlight potential links between the gut microbiota and IBS by discussing the current knowledge of the gut microbiota; it will also illustrate bacterial-host interactions and how alterations to these interactions could exacerbate, induce or even help alleviate IBS. PMID:25918261

  11. Gut microbiota and energy balance: role in obesity.

    PubMed

    Blaut, Michael

    2015-08-01

    The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gut microbiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long- and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated. PMID:25518735

  12. The role of gut hormone peptide YY in energy and glucose homeostasis: twelve years on.

    PubMed

    Manning, Sean; Batterham, Rachel L

    2014-01-01

    Although the role of peptide YY (PYY) as a regulator of energy homeostasis was first highlighted only in 2002, our understanding of the physiological role of PYY has since rapidly advanced. In recent years, insights from mechanistic studies in patients undergoing bariatric surgery, from pancreatic islet research, from functional neuroimaging studies, and from exercise research have greatly added to the field, and these areas provide the focus of discussion for this narrative review. We critically discuss recent findings relating to the role of PYY in mediating the beneficial effects of bariatric surgery, the role of PYY in glucose homeostasis, the role of hepatoportal PYY in mediating its central physiological effects, the specific modulation of brain regions by PYY, and the exercise-induced PYY response. PMID:24188711

  13. Naloxone does not Affect the Luteinizing Hormone-Releasing Hormone-Induced Inhibition of Luteinizing Hormone Secretion in Sheep.

    PubMed

    Naylor, A M; Porter, D W; Lincoln, D W

    1989-06-01

    Abstract Injection of luteinizing hormone-releasing hormone (21 pmol) into the third cerebral ventricle of long-term ovariectomized ewes caused a marked inhibition of luteinizing hormone secretion. Mean luteinizing hormone levels and luteinizing hormone pulse frequency were reduced significantly when compared with the control responses to saline (50 mul). A notable characteristic of the response was the delayed and sustained nature of the luteinizing hormone-releasing hormone-induced inhibition. In the presence of the opioid antagonist naloxone (4 +/- 25 mg iv), the central administration of luteinizing hormone-releasing hormone still produced a marked inhibition of luteinizing hormone secretion. Again, mean luteinizing hormone levels and luteinizing hormone pulse frequency were reduced significantly. When naloxone was injected iv, there was a significant rise in mean luteinizing hormone levels as a consequence of an increase in pulse frequency (in four out of five ewes) and a significant increase in luteinizing hormone pulse amplitude. In conclusion, these data suggest that central opioid pathways sensitive to blockade by naloxone are not involved in the luteinizing hormone-releasing hormone-induced inhibition of luteinizing hormone release. Furthermore, in the long-term ovariectomized ewe, endogenous opioid peptides exert a tonic inhibitory influence on luteinizing hormone-releasing hormone/luteinizing hormone secretion. PMID:19210459

  14. Hormonal contraception and lactation.

    PubMed

    Kelsey, J J

    1996-12-01

    Hormonal contraceptive measures can be used immediately postpartum if the patient so desires. Progestin-only contraceptives are preferable to estrogen-containing methods if initiated during the first six months after delivery. Progestin only contraceptives do not appear to affect milk volume, composition, or to cause deleterious effects in the infant. Ideally for women who desire a form of contraception in addition to lactation-induced amenorrhea, progestin-only methods should be started at six weeks postpartum if the woman is fully breastfeeding. Since contraception protection is provided by lactation amenorrhea, the six week delay will decrease infant exposure to exogenous hormones and decrease the incidence of irregular postpartum bleeding. Milk volume may decrease with the use of estrogen; however, no detrimental effects have been shown on infant growth or development. For women who are planning to gradually wean their infant, use of COCs may provide an easier transition to bottle-feeding. COCs should be used with caution by women who are not able to obtain supplemental milk. A decrease in milk volume can lead to earlier discontinuation of the hormonal contraceptive in an attempt to increase milk quantity. Supplementation is often needed, and then the woman ovulates again, possibly resulting in an unintended pregnancy. Many women are motivated immediately postpartum to accept contraception. For other women, lack of access to health care may provide barriers in obtaining adequate contraception later. In either case, there are adequate data to show no detriments of starting progestin-only contraceptives within days of delivery. Therefore, the best method for the patient should be employed to ensure adequate contraception while preserving optimal lactation. PMID:9025449

  15. Regulation of Lactobacillus casei Sorbitol Utilization Genes Requires DNA-Binding Transcriptional Activator GutR and the Conserved Protein GutM▿

    PubMed Central

    Alcántara, Cristina; Sarmiento-Rubiano, Luz Adriana; Monedero, Vicente; Deutscher, Josef; Pérez-Martínez, Gaspar; Yebra, María J.

    2008-01-01

    Sequence analysis of the five genes (gutRMCBA) downstream from the previously described sorbitol-6-phosphate dehydrogenase-encoding Lactobacillus casei gutF gene revealed that they constitute a sorbitol (glucitol) utilization operon. The gutRM genes encode putative regulators, while the gutCBA genes encode the EIIC, EIIBC, and EIIA proteins of a phosphoenolpyruvate-dependent sorbitol phosphotransferase system (PTSGut). The gut operon is transcribed as a polycistronic gutFRMCBA messenger, the expression of which is induced by sorbitol and repressed by glucose. gutR encodes a transcriptional regulator with two PTS-regulated domains, a galactitol-specific EIIB-like domain (EIIBGat domain) and a mannitol/fructose-specific EIIA-like domain (EIIAMtl domain). Its inactivation abolished gut operon transcription and sorbitol uptake, indicating that it acts as a transcriptional activator. In contrast, cells carrying a gutB mutation expressed the gut operon constitutively, but they failed to transport sorbitol, indicating that EIIBCGut negatively regulates GutR. A footprint analysis showed that GutR binds to a 35-bp sequence upstream from the gut promoter. A sequence comparison with the presumed promoter region of gut operons from various firmicutes revealed a GutR consensus motif that includes an inverted repeat. The regulation mechanism of the L. casei gut operon is therefore likely to be operative in other firmicutes. Finally, gutM codes for a conserved protein of unknown function present in all sequenced gut operons. A gutM mutant, the first constructed in a firmicute, showed drastically reduced gut operon expression and sorbitol uptake, indicating a regulatory role also for GutM. PMID:18676710

  16. Thyroid Hormone, Cancer, and Apoptosis.

    PubMed

    Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

    2016-01-01

    Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. PMID:27347891

  17. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  18. Impacts of Plant-Based Foods in Ancestral Hominin Diets on the Metabolism and Function of Gut Microbiota In Vitro

    PubMed Central

    Walton, Gemma E.; Swann, Jonathan R.; Psichas, Arianna; Costabile, Adele; Johnson, Laura P.; Sponheimer, Matt; Gibson, Glenn R.; Barraclough, Timothy G.

    2014-01-01

    ABSTRACT Ancestral human populations had diets containing more indigestible plant material than present-day diets in industrialized countries. One hypothesis for the rise in prevalence of obesity is that physiological mechanisms for controlling appetite evolved to match a diet with plant fiber content higher than that of present-day diets. We investigated how diet affects gut microbiota and colon cells by comparing human microbial communities with those from a primate that has an extreme plant-based diet, namely, the gelada baboon, which is a grazer. The effects of potato (high starch) versus grass (high lignin and cellulose) diets on human-derived versus gelada-derived fecal communities were compared in vitro. We especially focused on the production of short-chain fatty acids, which are hypothesized to be key metabolites influencing appetite regulation pathways. The results confirmed that diet has a major effect on bacterial numbers, short-chain fatty acid production, and the release of hormones involved in appetite suppression. The potato diet yielded greater production of short-chain fatty acids and hormone release than the grass diet, even in the gelada cultures, which we had expected should be better adapted to the grass diet. The strong effects of diet on hormone release could not be explained, however, solely by short-chain fatty acid concentrations. Nuclear magnetic resonance spectroscopy found changes in additional metabolites, including betaine and isoleucine, that might play key roles in inhibiting and stimulating appetite suppression pathways. Our study results indicate that a broader array of metabolites might be involved in triggering gut hormone release in humans than previously thought. PMID:24846385

  19. A Tick Gut Protein with Fibronectin III Domains Aids Borrelia burgdorferi Congregation to the Gut during Transmission

    PubMed Central

    Schuijt, Tim J.; Boder, Eric; Hovius, Joppe W.; Fikrig, Erol

    2014-01-01

    Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands. This complex process, involving intimate interactions of the spirochete with the gut epithelium, is pivotal to transmission. We utilized a yeast surface display library of tick gut proteins to perform a global screen for tick gut proteins that might interact with Borrelia membrane proteins. A putative fibronectin type III domain-containing tick gut protein (Ixofin3D) was most frequently identified from this screen and prioritized for further analysis. Immunization against Ixofin3D and RNA interference-mediated reduction in expression of Ixofin3D resulted in decreased spirochete burden in tick salivary glands and in the murine host. Microscopic examination showed decreased aggregation of spirochetes on the gut epithelium concomitant with reduced expression of Ixofin3D. Our observations suggest that the interaction between Borrelia and Ixofin3D facilitates spirochete congregation to the gut during transmission, and provides a “molecular exit” direction for spirochete egress from the gut. PMID:25102051

  20. Influence of Photoperiod on Hormones, Behavior, and Immune Function

    PubMed Central

    Walton, James C.; Weil, Zachary M.; Nelson, Randy J.

    2011-01-01

    Photoperiodism is the ability of plants and animals to measure environmental day length to ascertain time of year. Central to the evolution of photoperiodism in animals is the adaptive distribution of energetically challenging activities across the year to optimize reproductive fitness while balancing the energetic tradeoffs necessary for seasonally- appropriate survival strategies. The ability to accurately predict future events requires endogenous mechanisms to permit physiological anticipation of annual conditions. Day length provides a virtually noise free environmental signal to monitor and accurately predict time of the year. In mammals, melatonin provides the hormonal signal transducing day length. Duration of pineal melatonin is inversely related to day length and its secretion drives enduring changes in many physiological systems, including the HPA, HPG, and brain-gut axes, the autonomic nervous system, and the immune system. Thus, melatonin is the fulcrum mediating redistribution of energetic investment among physiological processes to maximize fitness and survival. PMID:21156187

  1. Salmonella Transiently Reside in Luminal Neutrophils in the Inflamed Gut

    PubMed Central

    Loetscher, Yvonne; Wieser, Andreas; Lengefeld, Jette; Kaiser, Patrick; Schubert, Sören; Heikenwalder, Mathias; Hardt, Wolf-Dietrich; Stecher, Bärbel

    2012-01-01

    Background Enteric pathogens need to grow efficiently in the gut lumen in order to cause disease and ensure transmission. The interior of the gut forms a complex environment comprising the mucosal surface area and the inner gut lumen with epithelial cell debris and food particles. Recruitment of neutrophils to the intestinal lumen is a hallmark of non-typhoidal Salmonella enterica infections in humans. Here, we analyzed the interaction of gut luminal neutrophils with S. enterica serovar Typhimurium (S. Tm) in a mouse colitis model. Results Upon S. Tmwt infection, neutrophils transmigrate across the mucosa into the intestinal lumen. We detected a majority of pathogens associated with luminal neutrophils 20 hours after infection. Neutrophils are viable and actively engulf S. Tm, as demonstrated by live microscopy. Using S. Tm mutant strains defective in tissue invasion we show that pathogens are mostly taken up in the gut lumen at the epithelial barrier by luminal neutrophils. In these luminal neutrophils, S. Tm induces expression of genes typically required for its intracellular lifestyle such as siderophore production iroBCDE and the Salmonella pathogenicity island 2 encoded type three secretion system (TTSS-2). This shows that S. Tm at least transiently survives and responds to engulfment by gut luminal neutrophils. Gentamicin protection experiments suggest that the life-span of luminal neutrophils is limited and that S. Tm is subsequently released into the gut lumen. This “fast cycling” through the intracellular compartment of gut luminal neutrophils would explain the high fraction of TTSS-2 and iroBCDE expressing intra- and extracellular bacteria in the lumen of the infected gut. Conclusion In conclusion, live neutrophils recruited during acute S. Tm colitis engulf pathogens in the gut lumen and may thus actively engage in shaping the environment of pathogens and commensals in the inflamed gut. PMID:22493718

  2. Isolation, identification, and characterization of gut microflora of Perionyx excavatus collected from Midnapore, West Bengal.

    PubMed

    Samanta, Tanushree Tulsian; Das, Ankita

    2016-03-01

    Agriculture is an important part of the economy of the undivided Midnapore district. Agricultural land is its asset and most importantly its means of sustenance as well as survival. Earthworms are invertebrates that play a key role in recycling organic matters in soils. Since the intestines of earthworms harbor wide ranges of microorganisms, enzymes, hormones etc., these half digested materials decompose rapidly and are transformed into a stabilized material called vermicompost which is very useful for increasing the soil fertility. One has to look for these characters before recommending any species for vermiculture. In the present study, Perionyx excavatus specimens were collected from the undivided Midnapore district and from the Earthworms gut, bacteria, fungus, actinobacteria, and yeast were isolated and identified using various morphological and biochemical tests. All the bacterial isolates were identified using morphological study, staining techniques, and different biochemical tests such as catalase test, KOH test, H2 SO4 test, Starch hydrolysis test, oxidase test, and sucrose hydrolysis test. All the fungal, actinobacteria, and yeast isolates were subjected to staining and morphological characterization (color and texture of fungal colony). Bacterial isolates of genus Bacillus sp., Staphylococcus sp., Enterococci, Micrococcus sp., Enterobacter sp., and Citrobacter sp. were identified. Among the fungal isolates Aspergilus sp., and P. boydii were identified. Streptomyces sp., Nocardia sp. among the actinobacteria and Candida sp. among yeast were also found to be present in earthworm gut and these might play an important role along with the earthworm to increase the quality and fertility of soil. PMID:26821782

  3. Recent Advances in Gut Nutrient Chemosensing

    PubMed Central

    Nguyen, C.A.; Akiba, Y.; Kaunitz, J.D.

    2016-01-01

    The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid-sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long-chain fatty acids with GPR120 activated by medium- and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT-1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity. PMID:22300073

  4. Manipulating the Gut Microbiota: Methods and Challenges.

    PubMed

    Ericsson, Aaron C; Franklin, Craig L

    2015-01-01

    Eukaryotic organisms are colonized by rich and dynamic communities of microbes, both internally (e.g., in the gastrointestinal and respiratory tracts) and externally (e.g., on skin and external mucosal surfaces). The vast majority of bacterial microbes reside in the lower gastrointestinal (GI) tract, and it is estimated that the gut of a healthy human is home to some 100 trillion bacteria, roughly an order of magnitude greater than the number of host somatic cells. The development of culture-independent methods to characterize the gut microbiota (GM) has spurred a renewed interest in its role in host health and disease. Indeed, associations have been identified between various changes in the composition of the GM and an extensive list of diseases, both enteric and systemic. Animal models provide a means whereby causal relationships between characteristic differences in the GM and diseases or conditions can be formally tested using genetically identical animals in highly controlled environments. Clearly, the GM and its interactions with the host and myriad environmental factors are exceedingly complex, and it is rare that a single microbial taxon associates with, much less causes, a phenotype with perfect sensitivity and specificity. Moreover, while the exact numbers are the subject of debate, it is well recognized that only a minority of gut bacteria can be successfully cultured ex vivo. Thus, to perform studies investigating causal roles of the GM in animal model phenotypes, researchers need clever techniques to experimentally manipulate the GM of animals, and several ingenious methods of doing so have been developed, each providing its own type of information and with its own set of advantages and drawbacks. The current review will focus on the various means of experimentally manipulating the GM of research animals, drawing attention to the factors that would aid a researcher in selecting an experimental approach, and with an emphasis on mice and rats, the

  5. Gut Dysbiosis in Patients with Anorexia Nervosa

    PubMed Central

    Morita, Chihiro; Tsuji, Hirokazu; Hata, Tomokazu; Gondo, Motoharu; Takakura, Shu; Kawai, Keisuke; Yoshihara, Kazufumi; Ogata, Kiyohito; Nomoto, Koji; Miyazaki, Kouji; Sudo, Nobuyuki

    2015-01-01

    Anorexia nervosa (AN) is a psychological illness with devastating physical consequences; however, its pathophysiological mechanism remains unclear. Because numerous reports have indicated the importance of gut microbiota in the regulation of weight gain, it is reasonable to speculate that AN patients might have a microbial imbalance, i.e. dysbiosis, in their gut. In this study, we compared the fecal microbiota of female patients with AN (n = 25), including restrictive (ANR, n = 14) and binge-eating (ANBP, n = 11) subtypes, with those of age-matched healthy female controls (n = 21) using the Yakult Intestinal Flora-SCAN based on 16S or 23S rRNA–targeted RT–quantitative PCR technology. AN patients had significantly lower amounts of total bacteria and obligate anaerobes including those from the Clostridium coccoides group, Clostridium leptum subgroup, and Bacteroides fragilis group than the age-matched healthy women. Lower numbers of Streptococcus were also found in the AN group than in the control group. In the analysis based on AN subtypes, the counts of the Bacteroides fragilis group in the ANR and ANBP groups and the counts of the Clostridium coccoides group in the ANR group were significantly lower than those in the control group. The detection rate of the Lactobacillus plantarum subgroup was significantly lower in the AN group than in the control group. The AN group had significantly lower acetic and propionic acid concentrations in the feces than the control group. Moreover, the subtype analysis showed that the fecal concentrations of acetic acid were lower in the ANR group than in the control group. Principal component analysis confirmed a clear difference in the bacterial components between the AN patients and healthy women. Collectively, these results clearly indicate the existence of dysbiosis in the gut of AN patients. PMID:26682545

  6. Human gut microbiota: does diet matter?

    PubMed

    Maukonen, Johanna; Saarela, Maria

    2015-02-01

    The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated. PMID:25156389

  7. Microbiota and Neurological Disorders: A Gut Feeling.

    PubMed

    Moos, Walter H; Faller, Douglas V; Harpp, David N; Kanara, Iphigenia; Pernokas, Julie; Powers, Whitney R; Steliou, Kosta

    2016-01-01

    In the past century, noncommunicable diseases have surpassed infectious diseases as the principal cause of sickness and death, worldwide. Trillions of commensal microbes live in and on our body, and constitute the human microbiome. The vast majority of these microorganisms are maternally derived and live in the gut, where they perform functions essential to our health and survival, including: digesting food, activating certain drugs, producing short-chain fatty acids (which help to modulate gene expression by inhibiting the deacetylation of histone proteins), generating anti-inflammatory substances, and playing a fundamental role in the induction, training, and function of our immune system. Among the many roles the microbiome ultimately plays, it mitigates against untoward effects from our exposure to the environment by forming a biotic shield between us and the outside world. The importance of physical activity coupled with a balanced and healthy diet in the maintenance of our well-being has been recognized since antiquity. However, it is only recently that characterization of the host-microbiome intermetabolic and crosstalk pathways has come to the forefront in studying therapeutic design. As reviewed in this report, synthetic biology shows potential in developing microorganisms for correcting pathogenic dysbiosis (gut microbiota-host maladaptation), although this has yet to be proven. However, the development and use of small molecule drugs have a long and successful history in the clinic, with small molecule histone deacetylase inhibitors representing one relevant example already approved to treat cancer and other disorders. Moreover, preclinical research suggests that epigenetic treatment of neurological conditions holds significant promise. With the mouth being an extension of the digestive tract, it presents a readily accessible diagnostic site for the early detection of potential unhealthy pathogens resident in the gut. Taken together, the data outlined

  8. Environmental and Gut Bacteroidetes: The Food Connection

    PubMed Central

    Thomas, François; Hehemann, Jan-Hendrik; Rebuffet, Etienne; Czjzek, Mirjam; Michel, Gurvan

    2011-01-01

    Members of the diverse bacterial phylum Bacteroidetes have colonized virtually all types of habitats on Earth. They are among the major members of the microbiota of animals, especially in the gastrointestinal tract, can act as pathogens and are frequently found in soils, oceans and freshwater. In these contrasting ecological niches, Bacteroidetes are increasingly regarded as specialists for the degradation of high molecular weight organic matter, i.e., proteins and carbohydrates. This review presents the current knowledge on the role and mechanisms of polysaccharide degradation by Bacteroidetes in their respective habitats. The recent sequencing of Bacteroidetes genomes confirms the presence of numerous carbohydrate-active enzymes covering a large spectrum of substrates from plant, algal, and animal origin. Comparative genomics reveal specific Polysaccharide Utilization Loci shared between distantly related members of the phylum, either in environmental or gut-associated species. Moreover, Bacteroidetes genomes appear to be highly plastic and frequently reorganized through genetic rearrangements, gene duplications and lateral gene transfers (LGT), a feature that could have driven their adaptation to distinct ecological niches. Evidence is accumulating that the nature of the diet shapes the composition of the intestinal microbiota. We address the potential links between gut and environmental bacteria through food consumption. LGT can provide gut bacteria with original sets of utensils to degrade otherwise refractory substrates found in the diet. A more complete understanding of the genetic gateways between food-associated environmental species and intestinal microbial communities sheds new light on the origin and evolution of Bacteroidetes as animals’ symbionts. It also raises the question as to how the consumption of increasingly hygienic and processed food deprives our microbiota from useful environmental genes and possibly affects our health. PMID:21747801

  9. Gut Dysbiosis in Patients with Anorexia Nervosa.

    PubMed

    Morita, Chihiro; Tsuji, Hirokazu; Hata, Tomokazu; Gondo, Motoharu; Takakura, Shu; Kawai, Keisuke; Yoshihara, Kazufumi; Ogata, Kiyohito; Nomoto, Koji; Miyazaki, Kouji; Sudo, Nobuyuki

    2015-01-01

    Anorexia nervosa (AN) is a psychological illness with devastating physical consequences; however, its pathophysiological mechanism remains unclear. Because numerous reports have indicated the importance of gut microbiota in the regulation of weight gain, it is reasonable to speculate that AN patients might have a microbial imbalance, i.e. dysbiosis, in their gut. In this study, we compared the fecal microbiota of female patients with AN (n = 25), including restrictive (ANR, n = 14) and binge-eating (ANBP, n = 11) subtypes, with those of age-matched healthy female controls (n = 21) using the Yakult Intestinal Flora-SCAN based on 16S or 23S rRNA-targeted RT-quantitative PCR technology. AN patients had significantly lower amounts of total bacteria and obligate anaerobes including those from the Clostridium coccoides group, Clostridium leptum subgroup, and Bacteroides fragilis group than the age-matched healthy women. Lower numbers of Streptococcus were also found in the AN group than in the control group. In the analysis based on AN subtypes, the counts of the Bacteroides fragilis group in the ANR and ANBP groups and the counts of the Clostridium coccoides group in the ANR group were significantly lower than those in the control group. The detection rate of the Lactobacillus plantarum subgroup was significantly lower in the AN group than in the control group. The AN group had significantly lower acetic and propionic acid concentrations in the feces than the control group. Moreover, the subtype analysis showed that the fecal concentrations of acetic acid were lower in the ANR group than in the control group. Principal component analysis confirmed a clear difference in the bacterial components between the AN patients and healthy women. Collectively, these results clearly indicate the existence of dysbiosis in the gut of AN patients. PMID:26682545

  10. Microbiota and Neurological Disorders: A Gut Feeling

    PubMed Central

    Moos, Walter H.; Faller, Douglas V.; Harpp, David N.; Kanara, Iphigenia; Pernokas, Julie; Powers, Whitney R.; Steliou, Kosta

    2016-01-01

    Abstract In the past century, noncommunicable diseases have surpassed infectious diseases as the principal cause of sickness and death, worldwide. Trillions of commensal microbes live in and on our body, and constitute the human microbiome. The vast majority of these microorganisms are maternally derived and live in the gut, where they perform functions essential to our health and survival, including: digesting food, activating certain drugs, producing short-chain fatty acids (which help to modulate gene expression by inhibiting the deacetylation of histone proteins), generating anti-inflammatory substances, and playing a fundamental role in the induction, training, and function of our immune system. Among the many roles the microbiome ultimately plays, it mitigates against untoward effects from our exposure to the environment by forming a biotic shield between us and the outside world. The importance of physical activity coupled with a balanced and healthy diet in the maintenance of our well-being has been recognized since antiquity. However, it is only recently that characterization of the host–microbiome intermetabolic and crosstalk pathways has come to the forefront in studying therapeutic design. As reviewed in this report, synthetic biology shows potential in developing microorganisms for correcting pathogenic dysbiosis (gut microbiota–host maladaptation), although this has yet to be proven. However, the development and use of small molecule drugs have a long and successful history in the clinic, with small molecule histone deacetylase inhibitors representing one relevant example already approved to treat cancer and other disorders. Moreover, preclinical research suggests that epigenetic treatment of neurological conditions holds significant promise. With the mouth being an extension of the digestive tract, it presents a readily accessible diagnostic site for the early detection of potential unhealthy pathogens resident in the gut. Taken together, the

  11. Molecular Tools for Investigating the Gut Microbiota

    NASA Astrophysics Data System (ADS)

    Lay, Christophe

    The “microbial world within us” (Zoetendal et al., 2006) is populated by a complex society of indigenous microorganisms that feature different “ethnic” populations. Those microbial cells thriving within us are estimated to outnumber human body cells by a factor of ten to one. Insights into the relation between the intestinal microbial community and its host have been gained through gnotobiology. Indeed, the influence of the gut microbiota upon human development, physiology, immunity, and nutrition has been inferred by comparing gnotoxenic and axenic murine models (Hooper et al., 1998, 2002, 2003; Hooper and Gordon, 2001).

  12. Non-minimal inflation and SUSY GUTs

    SciTech Connect

    Okada, Nobuchika

    2012-07-27

    The Standard Model Higgs boson with the nonminimal coupling to the gravitational curvature can drive cosmological inflation. We study this type of inflationary scenario in the context of supergravity. We first point out that it is naturally implemented in the minimal supersymmetric SU(5) model, and hence virtually in any GUT models. Next we propose another scenario based on the Minimal Supersymmetric Standard Model supplemented by the right-handed neutrinos. These models can be tested by new observational data from the Planck satellite experiments within a few years.

  13. F-Theory Uplifts and GUTs

    SciTech Connect

    Blumenhagen, Ralph; Grimm, Thomas W.; Jurke, Benjamin; Weigand, Timo; /SLAC

    2010-08-26

    We study the F-theory uplift of Type IIB orientifold models on compact Calabi-Yau threefolds containing divisors which are del Pezzo surfaces. We consider two examples defined via del Pezzo transitions of the quintic. The first model has an orientifold projection leading to two disjoint O7-planes and the second involution acts via an exchange of two del Pezzo surfaces. The two uplifted fourfolds are generically singular with minimal gauge enhancements over a divisor and, respectively, a curve in the non-Fano base. We study possible further degenerations of the elliptic fiber leading to F-theory GUT models based on subgroups of E{sub 8}.

  14. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats

    PubMed Central

    Paul, Heather A.; Bomhof, Marc R.; Vogel, Hans J.; Reimer, Raylene A.

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

  15. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

    PubMed

    Paul, Heather A; Bomhof, Marc R; Vogel, Hans J; Reimer, Raylene A

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

  16. Hormonal control of inflammatory responses

    PubMed Central

    Farsky, Sandra P.

    1993-01-01

    Almost any stage of inflammatory and immunological responses is affected by hormone actions. This provides the basis for the suggestion that hormones act as modulators of the host reaction against trauma and infection. Specific hormone receptors are detected in the reactive structures in inflamed areas and binding of hormone molecules to such receptors results in the generation of signals that influence cell functions relevant for the development of inflammatory responses. Diversity of hormonal functions accounts for recognized pro- and anti-inflammatory effects exerted by these substances. Most hormone systems are capable of influencing inflammatory events. Insulin and glucocorticoids, however, exert direct regulatory effects at concentrations usually found in plasma. Insulin is endowed with facilitatory actions on vascular reactivity to inflammatory mediators and inflammatory cell functions. Increased concentrations of circulating glucocorticoids at the early stages of inflammation results in downregulation of inflammatory responses. Oestrogens markedly reduce the response to injury in a variety of experimental models. Glucagon and thyroid hormones exert indirect anti-inflammatory effects mediated by the activity of the adrenal cortex. Accordingly, inflammation is not only merely a local response, but a hormone-controlled process. PMID:18475521

  17. Homeostasis, thymic hormones and aging.

    PubMed

    Goya, R G; Bolognani, F

    1999-01-01

    The thymic-pituitary axis constitutes a bidirectional circuit where the ascending feedback loop is effected by thymic factors of epithelial origin. The aim of the present article is, first, to introduce the idea of an immune-neuroendocrine homeostatic network in higher animals. Next, the relevance of the thymus in this network and the possible role of this gland in the neuroendocrine imbalances associated with aging are discussed. A number of studies are next reviewed which show that the endocrine thymus produces several bioactive molecules, generally called thymic hormones, which in addition to possessing immunoregulatory properties are also active on nervous and endocrine circuits. In particular, the reported activities of thymosin fraction five, thymosin alpha 1 and thymosin beta 4 on beta-endorphin, adrenocorticotropic hormone, glucocorticoids, luteinizing hormone-releasing hormone and luteinizing hormone secretion in different animal and cell models are reviewed. The known hypophysiotropic actions of other thymic hormones like thymulin, homeostatic thymus hormone and thymus factor are also summarized, and the impact of aging on pituitary responsiveness to thymic hormones is discussed. As a conclusion, it is proposed that in addition to its central role in the regulation of the immune function, the thymus gland may extend its influence to nonimmunologic components of the body, including the neuroendocrine system. The early onset of thymus involution might, therefore, act as a triggering event which would initiate the gradual decline in homeostatic potential that characterizes the aging process. PMID:10202264

  18. Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation

    PubMed Central

    Wolfs, Tim G. A. M.; Kramer, Boris W.; Thuijls, Geertje; Kemp, Matthew W.; Saito, Masatoshi; Willems, Monique G. M.; Senthamarai-Kannan, Paranthaman; Newnham, John P.; Jobe, Alan H.

    2014-01-01

    Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid. The gastrointestinal tract was isolated from the respiratory tract and the amnion/skin epithelia by fetal surgery in time-mated ewes. Lipopolysaccharide (LPS) or saline (controls) was selectively infused in the gastrointestinal tract, trachea, or amniotic compartment at 2 or 6 days before preterm delivery at 124 days gestation (term 150 days). Gastrointestinal and intratracheal LPS exposure caused distinct inflammatory responses in the fetal gut. Inflammatory responses could be distinguished by the influx of leukocytes (MPO+, CD3+, and FoxP3+ cells), tumor necrosis factor-α, and interferon-γ expression and differential upregulation of mRNA levels for Toll-like receptor 1, 2, 4, and 6. Fetal gut inflammation after direct intestinal LPS exposure resulted in severe loss of the tight junctional protein zonula occludens protein 1 (ZO-1) and increased mitosis of intestinal epithelial cells. Inflammation of the fetal gut after selective LPS instillation in the lungs caused only mild disruption of ZO-1, loss in epithelial cell integrity, and impaired epithelial differentiation. LPS exposure of the amnion/skin epithelia did not result in gut inflammation or morphological, structural, and functional changes. Our results indicate that the detrimental consequences of chorioamnionitis on fetal gut development are the combined result of local gut and lung-mediated inflammatory responses. PMID:24458021

  19. Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation.

    PubMed

    Wolfs, Tim G A M; Kramer, Boris W; Thuijls, Geertje; Kemp, Matthew W; Saito, Masatoshi; Willems, Monique G M; Senthamarai-Kannan, Paranthaman; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

    2014-03-01

    Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid. The gastrointestinal tract was isolated from the respiratory tract and the amnion/skin epithelia by fetal surgery in time-mated ewes. Lipopolysaccharide (LPS) or saline (controls) was selectively infused in the gastrointestinal tract, trachea, or amniotic compartment at 2 or 6 days before preterm delivery at 124 days gestation (term 150 days). Gastrointestinal and intratracheal LPS exposure caused distinct inflammatory responses in the fetal gut. Inflammatory responses could be distinguished by the influx of leukocytes (MPO(+), CD3(+), and FoxP3(+) cells), tumor necrosis factor-α, and interferon-γ expression and differential upregulation of mRNA levels for Toll-like receptor 1, 2, 4, and 6. Fetal gut inflammation after direct intestinal LPS exposure resulted in severe loss of the tight junctional protein zonula occludens protein 1 (ZO-1) and increased mitosis of intestinal epithelial cells. Inflammation of the fetal gut after selective LPS instillation in the lungs caused only mild disruption of ZO-1, loss in epithelial cell integrity, and impaired epithelial differentiation. LPS exposure of the amnion/skin epithelia did not result in gut inflammation or morphological, structural, and functional changes. Our results indicate that the detrimental consequences of chorioamnionitis on fetal gut development are the combined result of local gut and lung-mediated inflammatory responses. PMID:24458021

  20. Chronic zinc deficiency alters chick gut microbiota composition and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zinc (Zn) deficiency is a prevalent micronutrient insufficiency. Although the gut is a vital organ for Zn utilization, and Zn deficiency is associated with impaired intestinal permeability and a global decrease in gastrointestinal health, alterations in the gut microbial ecology of the host under co...

  1. Brain-gut-microbiota axis in Parkinson's disease.

    PubMed

    Mulak, Agata; Bonaz, Bruno

    2015-10-01

    Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD. PMID:26457021

  2. Gene expression profiling gut microbiota in different races of humans.

    PubMed

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-01-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome. PMID:26975620

  3. Challenges of metabolomics in human gut microbiota research.

    PubMed

    Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

    2016-08-01

    The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. PMID:27012595

  4. Development of the preterm infant gut microbiome: A research priority

    SciTech Connect

    Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.; Ashmeade, Terri L.; Miller, Elizabeth; Gilbert, Jack A.

    2014-10-13

    The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.

  5. The role of the gut microbiota in NAFLD.

    PubMed

    Leung, Christopher; Rivera, Leni; Furness, John B; Angus, Peter W

    2016-07-01

    NAFLD is now the most common cause of liver disease in Western countries. This Review explores the links between NAFLD, the metabolic syndrome, dysbiosis, poor diet and gut health. Animal studies in which the gut microbiota are manipulated, and observational studies in patients with NAFLD, have provided considerable evidence that dysbiosis contributes to the pathogenesis of NAFLD. Dysbiosis increases gut permeability to bacterial products and increases hepatic exposure to injurious substances that increase hepatic inflammation and fibrosis. Dysbiosis, combined with poor diet, also changes luminal metabolism of food substrates, such as increased production of certain short-chain fatty acids and alcohol, and depletion of choline. Changes to the microbiome can also cause dysmotility, gut inflammation and other immunological changes in the gut that might contribute to liver injury. Evidence also suggests that certain food components and lifestyle factors, which are known to influence the severity of NAFLD, do so at least in part by changing the gut microbiota. Improved methods of analysis of the gut microbiome, and greater understanding of interactions between dysbiosis, diet, environmental factors and their effects on the gut-liver axis should improve the treatment of this common liver disease and its associated disorders. PMID:27273168

  6. 21 CFR 878.4830 - Absorbable surgical gut suture.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Absorbable surgical gut suture. 878.4830 Section 878.4830 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4830 Absorbable surgical gut suture. (a) Identification. An...

  7. Gut Microbiota Cool-Down Burning Fat! The Immune Hypothesis.

    PubMed

    Burcelin, Remy; Pomié, Céline

    2016-02-01

    Obesity is characterized by gut microbiota dysbiosis and reduced thermogenic activity of brown adipose tissue. A recent study reveals that gut microbiota hampers the emergence of thermogenic brown fat cells named beige cells within white fat depots via a mechanism that involves the control of macrophages and eosinophil infiltration. PMID:26747615

  8. Gene expression profiling gut microbiota in different races of humans

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-03-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome.

  9. Development of the preterm infant gut microbiome: A research priority

    DOE PAGESBeta

    Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.; Ashmeade, Terri L.; Miller, Elizabeth; Gilbert, Jack A.

    2014-10-13

    The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role ofmore » the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.« less

  10. Brain-gut-microbiota axis in Parkinson's disease

    PubMed Central

    Mulak, Agata; Bonaz, Bruno

    2015-01-01

    Parkinson’s disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD. PMID:26457021

  11. Gut microbiota and colon cancer: the carbohydrate link

    PubMed Central

    Belcheva, Antoaneta; Martin, Alberto

    2015-01-01

    Understanding the complex pathophysiology of colorectal cancer and the interaction between host genetics, the gut microbiome, and diet has attracted significant attention in the last few years. The discovery that gut microbial metabolites may dictate the course of colorectal cancer progression supports the development of microbial-targeted strategies. PMID:27308387

  12. Gene expression profiling gut microbiota in different races of humans

    PubMed Central

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-01-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome. PMID:26975620

  13. Human gut microbiome viewed across age and geography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, we characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy child...

  14. The emerging relevance of the gut microbiome in cardiometabolic health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Host metabolic pathways and physiological responses are regulated by signals linking the host to the gut microbial community or microbiome. Here, we draw a spotlight on lipid and bile acid metabolism and inflammatory response as they pertain to cardiometabolic dysfunction. Gut microbial dysbiosis al...

  15. Types of Cancer Treatment: Hormone Therapy

    Cancer.gov

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  16. Genetics Home Reference: isolated growth hormone deficiency

    MedlinePlus

    ... Health Conditions isolated growth hormone deficiency isolated growth hormone deficiency Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Isolated growth hormone deficiency is a condition caused by a severe ...

  17. Hormonal changes during menopause.

    PubMed

    Al-Azzawi, Farook; Palacios, Santiago

    2009-06-20

    Ovarian senescence occurs gradually during the fourth and fifth decades of life, leading to menopause at an average age of about 51 years. This senescence results in a changing hormonal milieu, with decreases in the levels of estrogens and androgens. Similar changes may be induced by surgical menopause (bilateral oophorectomy) or ovarian failure resulting from cancer treatment. The declining levels of estrogens and androgens affect many tissues of the body and can produce a variety of signs and symptoms, including vasomotor symptoms, decreased bone density, changes in mood and energy, loss of pubic hair and changes in the genital tissues, and effects on sexual function. Accurate measurement of testosterone levels in postmenopausal women requires methods that are validated in the lower ranges of testosterone level observed in this population. PMID:19372016

  18. Impact of gut microbiota on the fly's germ line.

    PubMed

    Elgart, Michael; Stern, Shay; Salton, Orit; Gnainsky, Yulia; Heifetz, Yael; Soen, Yoav

    2016-01-01

    Unlike vertically transmitted endosymbionts, which have broad effects on their host's germ line, the extracellular gut microbiota is transmitted horizontally and is not known to influence the germ line. Here we provide evidence supporting the influence of these gut bacteria on the germ line of Drosophila melanogaster. Removal of the gut bacteria represses oogenesis, expedites maternal-to-zygotic-transition in the offspring and unmasks hidden phenotypic variation in mutants. We further show that the main impact on oogenesis is linked to the lack of gut Acetobacter species, and we identify the Drosophila Aldehyde dehydrogenase (Aldh) gene as an apparent mediator of repressed oogenesis in Acetobacter-depleted flies. The finding of interactions between the gut microbiota and the germ line has implications for reproduction, developmental robustness and adaptation. PMID:27080728

  19. Prevention and treatment of hepatic encephalopathy: focusing on gut microbiota.

    PubMed

    Garcovich, Matteo; Zocco, Maria Assunta; Roccarina, Davide; Ponziani, Francesca Romana; Gasbarrini, Antonio

    2012-12-14

    The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation. PMID:23239905

  20. Impact of gut microbiota on the fly's germ line

    PubMed Central

    Elgart, Michael; Stern, Shay; Salton, Orit; Gnainsky, Yulia; Heifetz, Yael; Soen, Yoav

    2016-01-01

    Unlike vertically transmitted endosymbionts, which have broad effects on their host's germ line, the extracellular gut microbiota is transmitted horizontally and is not known to influence the germ line. Here we provide evidence supporting the influence of these gut bacteria on the germ line of Drosophila melanogaster. Removal of the gut bacteria represses oogenesis, expedites maternal-to-zygotic-transition in the offspring and unmasks hidden phenotypic variation in mutants. We further show that the main impact on oogenesis is linked to the lack of gut Acetobacter species, and we identify the Drosophila Aldehyde dehydrogenase (Aldh) gene as an apparent mediator of repressed oogenesis in Acetobacter-depleted flies. The finding of interactions between the gut microbiota and the germ line has implications for reproduction, developmental robustness and adaptation. PMID:27080728