PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

PubMed

Voskuijl, W; de Lorijn, F; Verwijs, W; Hogeman, P; Heijmans, J; Mäkel, W; Taminiau, J; Benninga, M

2004-11-01

Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid. A test to distinguish colonic from small-intestinal permeability change.

PubMed

Jenkins, A P; Nukajam, W S; Menzies, I S; Creamer, B

1992-09-01

In normal adults intestinal permeation of ingested 51Cr-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of 51Cr-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and 51Cr-EDTA (50 microCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/l) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of 51Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (greater than 1.06%). In contrast, although seven colitics had a urinary excretion of 51Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and 51Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.

Standardising the Lactulose Mannitol Test of Gut Permeability to Minimise Error and Promote Comparability

PubMed Central

Sequeira, Ivana R.; Lentle, Roger G.; Kruger, Marlena C.; Hurst, Roger D.

2014-01-01

Background Lactulose mannitol ratio tests are clinically useful for assessing disorders characterised by changes in gut permeability and for assessing mixing in the intestinal lumen. Variations between currently used test protocols preclude meaningful comparisons between studies. We determined the optimal sampling period and related this to intestinal residence. Methods Half-hourly lactulose and mannitol urinary excretions were determined over 6 hours in 40 healthy female volunteers after administration of either 600 mg aspirin or placebo, in randomised order at weekly intervals. Gastric and small intestinal transit times were assessed by the SmartPill in 6 subjects from the same population. Half-hourly percentage recoveries of lactulose and mannitol were grouped on a basis of compartment transit time. The rate of increase or decrease of each sugar within each group was explored by simple linear regression to assess the optimal period of sampling. Key Results The between subject standard errors for each half-hourly lactulose and mannitol excretion were lowest, the correlation of the quantity of each sugar excreted with time was optimal and the difference between the two sugars in this temporal relationship maximal during the period from 2½-4 h after ingestion. Half-hourly lactulose excretions were generally increased after dosage with aspirin whilst those of mannitol were unchanged as was the temporal pattern and period of lowest between subject standard error for both sugars. Conclusion The results indicate that between subject variation in the percentage excretion of the two sugars would be minimised and the differences in the temporal patterns of excretion would be maximised if the period of collection of urine used in clinical tests of small intestinal permeability were restricted to 2½-4 h post dosage. This period corresponds to a period when the column of digesta column containing the probes is passing from the small to the large intestine. PMID:24901524

Lactulose promotes equol production and changes the microbial community during in vitro fermentation of daidzein by fecal inocula of sows.

PubMed

Zheng, Weijiang; Hou, Yanjun; Su, Yong; Yao, Wen

2014-02-01

Equol has higher biological effects than other isoflavones. However, only about 30-50% of humans possess a microbiota capable of producing equol from dietary daidzein. In recent years, interest has grown in dietary applications to improve equol production in human and other animals. In this study, lactulose was used as a potential equol-promoting prebiotic in vitro. The effect of lactulose on transformation of daidzein into equol by sows' fecal microbiota was investigated. Results showed that lactulose treatment improved bacteria growth parameters, changing the kinetics of fermentation in vitro. Lactulose significantly increased total gas production, T1/2, Tmax, and Rmax. Furthermore, lactulose altered the microflora composition, increased equol production associated with a reduction in the population of methanogen and increased the sulfate-reducing bacteria population during 24 h of incubation. Here, we report for the first time that in a certain condition (sealing or high pressure), via a dihydrodaidzein (DHD) pathway equol might be able to reform to daidzein by further metabolism using lactulose as a substrate. This study proposes that "hydrogen-producing prebiotic" might be a novel way to promote equol production in vivo or in vitro. Copyright © 2013 Elsevier Ltd. All rights reserved.

Treatment of Acute Hepatic Encephalopathy: Comparing the Effects of Adding Rifaximin to Lactulose on Patient Outcomes.

PubMed

Courson, Alesa; Jones, G Morgan; Twilla, Jennifer D

2016-06-01

Rifaximin is approved for the reduction of hepatic encephalopathy (HE) recurrence in patients with chronic liver disease (CLD); however, few studies have evaluated the benefit of adding rifaximin to lactulose for treatment of acute HE. The aim of this study was to determine the impact of combination therapy with lactulose and rifaximin on hospital length of stay (LOS) and readmission rates. A retrospective study of patients admitted to an adult hospital within the Methodist LeBonheur Healthcare (MLH) System in Memphis, Tennessee, between 2007 and 2012 was conducted. Patients were identified via International Classification of Diseases, Ninth Revision (ICD-9) coding for liver cirrhosis. Of the 173 patients included, 87 (50%) received lactulose monotherapy and 62 (36%) combination therapy, while 24 (14%) underwent therapy escalation. Median LOS was 6 days in monotherapy group and 8 days in combination group (P = .9). At 180 days, patients receiving combination therapy had fewer readmissions for HE than those receiving monotherapy (2.4% vs 16.2%, P = .02). Addition of rifaximin to lactulose for treatment of acute HE did not reduce hospital LOS; however, it did result in lower readmission rates for HE at 180 days. © The Author(s) 2015.

Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation.

PubMed

Attar, A; Lémann, M; Ferguson, A; Halphen, M; Boutron, M C; Flourié, B; Alix, E; Salmeron, M; Guillemot, F; Chaussade, S; Ménard, A M; Moreau, J; Naudin, G; Barthet, M

1999-02-01

Polyethylene glycol (PEG) 3350 is a non-absorbable, non-metabolised osmotic agent used in lavage solutions for gut cleansing. To compare the efficacy of PEG and lactulose in chronic constipation. A total of 115 patients with chronic constipation entered a multicentre, randomised, comparative trial. They initially received two sachets containing either PEG (13 g/sachet) or lactulose (10 g/sachet) and were given an option to change the dose to one or three sachets/day, depending on response. Ninety nine patients completed the trial. After four weeks, patients in the PEG group (n=50) had a higher number of stools and a lower median daily score for straining at stool than patients in the lactulose group (n=49). Overall improvement was greater in the PEG group. Clinical tolerance was similar in the two groups, but flatus was less frequently reported in the PEG group. The mean number of liquid stools was higher in the PEG group but the difference was significant only for the first two weeks. There were no serious adverse events and no significant change in laboratory tests in either group. At the end of the study, the number of sachets used by the patients was 1.6 (0.7)/day in the PEG group and 2.1 (0.7)/day in the lactulose group. Sixty one patients completed a further two months open study of one to three sachets PEG daily; there was no loss of efficacy and no serious toxicity. Low dose PEG 3350 was more effective than lactulose and better tolerated.

Effect of simethicone on lactulose-induced H2 production and gastrointestinal symptoms.

PubMed

Friis, H; Bodé, S; Rumessen, J J; Gudmand-Høyer, E

1991-01-01

The results of studies of the effect of simethicone on abdominal gas-related symptoms have been contradictory. In a randomized, double-blind cross-over study, 10 healthy volunteers were given 30 g lactulose and 600 mg simethicone or placebo. End-expiratory breath samples were collected and analyzed for H2 and gastrointestinal symptoms registered. There were no differences in biochemical parameters or symptom score between simethicone and placebo. In contrast to previous studies, we used a sufficiently large dose of lactulose to produce gastrointestinal symptoms, a higher dose of simethicone and placebo tablets containing the same additives as the simethicone tablets. There was no demonstrable effect of simethicone on symptoms or intestinal gas production caused by carbohydrate malabsorption.

Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution for Treatment of Overt Hepatic Encephalopathy

PubMed Central

Rahimi, Robert S.; Singal, Amit G.; Cuthbert, Jennifer A.; Rockey, Don C.

2017-01-01

IMPORTANCE Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. OBJECTIVE To compare polyethylene glycol 3350–electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. DESIGN, SETTING, AND PARTICIPANTS The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. INTERVENTIONS Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. MAIN OUTCOMES AND MEASURES The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. RESULTS A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely

Economic impact of low dose polyethylene glycol 3350 plus electrolytes compared with lactulose in the management of idiopathic constipation in the UK.

PubMed

Christie, Angela H; Culbert, Pearl; Guest, Julian F

2002-01-01

To estimate the economic impact of using low dose polyethyene glycol 3350 (PEG 3350) plus electrolytes (PEG+E) compared with lactulose in the treatment of idiopathic constipation in ambulant patients. DESIGN AND PERSPECTIVE: This was a decision analytic modelling study performed from the perspective of the UK's National Health Service (NHS). The clinical outcomes from a previously reported single-blind, randomised, multicentre trial were used as the clinical basis for the analysis. These data were combined with resource utilisation estimates derived from a panel of six general practitioners (GPs) and four nurses enabling a decision model to be constructed depicting the management of idiopathic constipation with either PEG+E or lactulose over 3 months. The model was used to estimate the expected 3-monthly NHS cost of using either laxative to manage idiopathic constipation. The expected 3-monthly NHS cost of using PEG+E or lactulose to manage idiopathic constipation was estimated to be 85 pound sterling and 96 pound sterling per patient, respectively (1999/2000 values). However, significantly more patients were successfully treated with PEG+E than lactulose (53% versus 24%; p < 0.001) at 3 months. GP visits were the primary cost driver for both PEG+E- and lactulose-treated patients, accounting for 56% (2.9 visits) and 73% (4.4 visits), respectively, of the expected NHS cost per patient at 3 months. Among PEG+E-treated patients, the acquisition cost of PEG+E was the secondary cost driver, accounting for 30% of the expected NHS cost per patient at 3 months, whereas the acquisition cost of lactulose accounted for only 11% of the expected NHS cost per lactulose-treated patient. District nurse domiciliary visits accounted for 4% and thyroid function tests for 2%. The costs of switched laxatives, concomitant laxatives, and gastroenterologist and colorectal surgeon visits collectively accounted for up to 9% of the total. The true cost of managing idiopathic constipation is

A randomised, double-blind study of polyethylene glycol 4000 and lactulose in the treatment of constipation in children

PubMed Central

2014-01-01

Background Chronic constipation is frequent in children. The objective of this study is to compare the efficacy and safety of PEG 4000 and lactulose for the treatment of chronic constipation in young children. Methods This randomised, double-blind study enrolled 88 young children aged 12 to 36 months, who were randomly assigned to receive lactulose (3.3 g per day) or PEG 4000 (8 g per day) for four weeks. The primary efficacy variable was stool frequency during the fourth week of treatment. Secondary outcomes were the number and frequency of subjective symptoms associated with defecation at each visit. Results Stool frequency was comparable in the two groups at baseline (lactulose: 0.7 ± 0.5; PEG 4000: 0.5 ± 0.55). Mean stool frequency increased from 0.70 ± 0.50 stools/day at baseline to 0.80 ± 0.41 at Week 4 in the lactulose group and from 0.50 ± 0.55 to 1.10 ± 0.55 stools/day in the PEG 4000 group. A significant difference was observed in the adjusted mean change from baseline, which was 0.15 stools/day in the lactulose group and 0.51 stools/day in the PEG 4000 group, with a least-squares mean difference of 0.36 stools/day [95% CI: 0.16 to 0.56]. With respect to secondary outcome variables, stool consistency and ease of stool passage improved more in the PEG 4000 group (p = 0.001). The incidence of adverse events was similar in both groups, the majority of which were mild. Conclusions PEG 4000 has superior efficacy to lactulose for the treatment of chronic constipation in young children and is well tolerated. Trial registration US National Institute of Health Clinical Trials database; study NCT00255372 first registered 17th November 2005. PMID:24943105

Validation of an LC-MS/MS Method for Urinary Lactulose and Mannitol Quantification: Results in Patients with Irritable Bowel Syndrome.

PubMed

Gervasoni, Jacopo; Schiattarella, Arcangelo; Giorgio, Valentina; Primiano, Aniello; Russo, Consuelo; Tesori, Valentina; Scaldaferri, Franco; Urbani, Andrea; Zuppi, Cecilia; Persichilli, Silvia

2016-01-01

Aim . Lactulose/mannitol ratio is used to assess intestinal barrier function. Aim of this work was to develop a robust and rapid method for the analysis of lactulose and mannitol in urine by liquid chromatography coupled to tandem mass spectrometry. Lactulose/mannitol ratio has been measured in pediatric patients suffering from irritable bowel syndrome. Methods . Calibration curves and raffinose, used as internal standard, were prepared in water : acetonitrile 20 : 80. Fifty μ L of urine sample was added to 450  μ L of internal standard solution. The chromatographic separation was performed using a Luna NH 2 column operating at a flow rate of 200  μ L/min and eluted with a linear gradient from 20% to 80% water in acetonitrile. Total run time is 9 minutes. The mass spectrometry operates in electrospray negative mode. Method was fully validated according to European Medicine Agency guidelines. Results and Conclusions . Linearity ranged from 10 to 1000 mg/L for mannitol and 2.5 to 1000 mg/L for lactulose. Imprecision in intra- and interassay was lower than 15% for both analytes. Accuracy was higher than 85%. Lactulose/mannitol ratio in pediatric patients is significantly higher than that measured in controls. The presented method, rapid and sensitive, is suitable in a clinical laboratory.

Efficient production of lactulose from whey powder by cellobiose 2-epimerase in an enzymatic membrane reactor.

PubMed

Wu, Lingtian; Xu, Cen; Li, Sha; Liang, Jinfeng; Xu, Hong; Xu, Zheng

2017-06-01

In this study, the gene encoding cellobiose 2-epimerase from Caldicellulosiruptor saccharolyticus (CsCE) was successfully expressed in Bacillus subtilis WB800. After the fermentation medium optimization, the activity of recombinant strain was 4.5-fold higher than the original medium in a 7.5L fermentor. The optimal catalytic pH and temperature of crude CsCE were 7.0 and 80°C, respectively. An enzymatic synthesis of lactulose was developed using cheese-whey lactose as its substrate. The maximum conversion rate of whey powder obtained was 58.5% using 7.5 U/mL CsCE. The enzymatic membrane reactor system exhibited a great operational stability, confirmed with the higher lactose conversion (42.4%) after 10 batches. To our best knowledge, this is the first report of lactulose synthesis in food grade strain, which improve the food safety, and we not only realize the biological production of lactulose, but also make good use of industrial waste, which have positive impact on environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular Monitoring of the Fecal Microbiota of Healthy Human Subjects during Administration of Lactulose and Saccharomyces boulardii

PubMed Central

Vanhoutte, Tom; De Preter, Vicky; De Brandt, Evie; Verbeke, Kristin; Swings, Jean; Huys, Geert

2006-01-01

Diet is a major factor in maintaining a healthy human gastrointestinal tract, and this has triggered the development of functional foods containing a probiotic and/or prebiotic component intended to improve the host's health via modulation of the intestinal microbiota. In this study, a long-term placebo-controlled crossover feeding study in which each subject received several treatments was performed to monitor the effect of a prebiotic substrate (i.e., lactulose), a probiotic organism (i.e., Saccharomyces boulardii), and their synbiotic combination on the fecal microbiota of three groups of 10 healthy human subjects differing in prebiotic dose and/or intake of placebo versus synbiotic. For this purpose, denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene amplicons was used to detect possible changes in the overall bacterial composition using the universal V3 primer and to detect possible changes at the subpopulation level using group-specific primers targeting the Bacteroides fragilis subgroup, the genus Bifidobacterium, the Clostridium lituseburense group (cluster XI), and the Clostridium coccoides-Eubacterium rectale group (cluster XIVa). Although these populations remained fairly stable based on DGGE profiling, one pronounced change was observed in the universal fingerprint profiles after lactulose ingestion. Band position analysis and band sequencing revealed that a band appearing or intensifying following lactulose administration could be assigned to the species Bifidobacterium adolescentis. Subsequent analysis with real-time PCR (RT-PCR) indicated a statistically significant increase (P < 0.05) in total bifidobacteria in one of the three subject groups after lactulose administration, whereas a similar but nonsignificant trend was observed in the other two groups. Combined RT-PCR results from two subject groups indicated a borderline significant increase (P = 0.074) of B. adolescentis following lactulose intake. The probiotic yeast S

Sleep disturbances in patients of liver cirrhosis with minimal hepatic encephalopathy before and after lactulose therapy.

PubMed

Singh, Jatinderpal; Sharma, Barjesh Chander; Puri, Vinod; Sachdeva, Sanjeev; Srivastava, Siddharth

2017-04-01

Sleep disturbances are common in patients of cirrhosis with minimal hepatic encephalopathy (MHE) and affect health related quality of life (HRQOL). No study has evaluated effect of lactulose on sleep disturbances and correlation with HRQOL in patients with MHE. We assessed sleep disturbances in cirrhosis with MHE and effect of lactulose on sleep disturbances and HRQOL. One hundred patients of cirrhosis [MHE; (n = 50, age 45.3 ± 11.2 years, 45 males) no-MHE (n = 50, age 46.3 ± 10.4 years, 44 males)] were included. MHE was diagnosed with psychometric hepatic encephalopathy score (PHES) ≤ -5. All patients underwent laboratory parameters including arterial ammonia and critical flicker frequency (CFF) Sleep disturbances were measured with Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and polysomnography. HRQOL was measured with SF-36(v2) questionnaire. Patients with MHE were given lactulose therapy for 3 months and all the parameters were repeated. Poor quality of sleep and excessive day time sleepiness were more common in patients with MHE, compared to without MHE. With lactulose therapy there was improvement in MHE in 21 patients and arterial ammonia levels (93.74 ± 14.8 vs. 71.44 ± 18.8 μmol/L: p < 0.001), CFF (34.83 ± 3.54 vs. 39.44 ± 4.95 Hz: p < 0.001), PHES (-7.64 ± 2.1 vs. -5.58 ± 2.09: p < 0.001), PSQI (8.6 ± 3.3 vs. 5.2 ± 1.5: p < 0.001), ESS (12.52 ± 3.01 vs. 9.24 ± 2.27: p < 0.001) and HRQOL (p = 0.01). Excessive day time sleepiness and impaired sleep quality are common in patients with MHE and correlate with neuropsychiatric impairment. Improvement in MHE with lactulose also leads to improvement in sleep disturbances and HRQOL.

Synthesis of Oligosaccharides Derived from Lactulose (OsLu) Using Soluble and Immobilized Aspergillus oryzae β-Galactosidase

PubMed Central

Cardelle-Cobas, Alejandra; Olano, Agustin; Irazoqui, Gabriela; Giacomini, Cecilia; Batista-Viera, Francisco; Corzo, Nieves; Corzo-Martínez, Marta

2016-01-01

β-Galactosidase from Aspergillus oryzae offers a high yield for the synthesis of oligosaccharides derived from lactulose (OsLu) by transgalactosylation. Oligosaccharides with degree of polymerization (DP) ≥ 3 have shown to possess higher in vitro bifidogenic effect than di- and tetrasaccharides. Thus, in this work, an optimization of reaction conditions affecting the specific selectivity of A. oryzae β-galactosidase for synthesis of OsLu has been carried out to enhance OsLu with DP ≥ 3 production. Assays with β-galactosidase immobilized onto a glutaraldehyde–agarose support were also carried out with the aim of making the process cost-effective and industrially viable. Optimal conditions with both soluble and immobilized enzyme for the synthesis of OsLu with DP ≥ 3 were 50 °C, pH 6.5, 450 g/L of lactulose, and 8 U/mL of enzyme, reaching yields of ca. 50% (w/v) of total OsLu and ca. 20% (w/v) of OsLu with DP 3, being 6′-galactosyl-lactulose the major one, after a short reaction time. Selective formation of disaccharides, however, was favored at 60 °C, pH 4.5, 450 g/L of lactulose and 8 U/mL of enzyme. Immobilization increased the enzymatic stability to temperature changes and allowed to reuse the enzyme. We can conclude that the use, under determined optimal conditions, of the A. oryzae β-galactosidase immobilized on a support of glutaraldehyde–agarose constitutes an efficient and cost-effective alternative to the use of soluble β-galactosidases for the synthesis of prebiotic OsLu mixtures. PMID:27014684

Effect of dietary lactulose supplementation on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers.

PubMed

Zhao, P Y; Li, H L; Mohammadi, M; Kim, I H

2016-01-01

A 35 d trial was conducted to evaluate the effects of dietary lactulose on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers. A total of 816 1-day-old male Ross broilers (40.2 ± 0.4 g) were allotted to 4 dietary treatments using 12 cages with 17 chicks per cage. Treatments were: 1) CON, basal diet; 2) L05, CON + 0.05% lactulose; 3) L10, CON + 0.10% lactulose; and 4) L15, CON + 0.15% lactulose. Higher (P < 0.05) body weight gain (BWG) and lower (P < 0.05) feed conversion ratio (FCR) were observed in broilers fed the L15 diet compared with those fed the CON diet during d 22 to 35. During d 0 to 35, BWG was higher (P < 0.05) and FCR was lower (P < 0.05) in broilers fed lactulose diets than those fed the CON diet. Additionally, broilers fed L15 diets had the highest BWG (P < 0.05) and lowest FCR (P < 0.05). The apparent total tract digestibility (ATTD) of DM and nitrogen (N) was increased (P < 0.05) in broilers fed the L15 diet compared with those fed the CON diet. Drip loss was decreased (P < 0.05) in L10 and L15 treatments compared with CON treatment on d 1, d 3, and d 5. On d 3, lowest (P < 0.05) drip loss was observed in the L15 treatment. Excreta E. coli counts in the L15 treatment were decreased (P < 0.05) on d 14, but Lactobacillus counts in the L15 treatment were increased (P < 0.05) on d 14 and d 35 compared with the CON diet. A linear effect (P < 0.05) was observed on BWG (d 22 to 35), FCR (d 0 to 35), the ATTD of DM and N, drip loss, E. coli (d 14), and Lactobacillus (d 14 and d 35) counts. In conclusion, dietary supplementation of 0.15% lactulose can improve growth performance and nutrient digestibility; as well as increase the proliferation of Lactobacillus and decrease E. coli counts in excreta. © 2015 Poultry Science Association Inc.

An efficient process for obtaining prebiotic oligosaccharides derived from lactulose using isomerized and purified whey permeate.

PubMed

Sabater, Carlos; Olano, Agustín; Prodanov, Marin; Montilla, Antonia; Corzo, Nieves

2017-12-01

One of the most promising uses of whey permeate (WP) is the synthesis of prebiotic oligosaccharides. Herein, commercial WP was submitted to chemical isomerization catalysed by sodium borate at an alkaline pH and subsequent purification using anion-exchange resins to remove boron. Subsequently, purified mixtures were used to synthesize prebiotic oligosaccharides using β-galactosidase from Bacillus circulans. Isomerization of concentrated WP (200 g L -1 lactose) gave rise to levels of lactulose up to 155.5 g L -1 after 30 min of reaction (molar ratio of boron/lactose, 1/1; pH 12; 70 °C). Boron was removed from the isomerized WP (IWP) using the combination of a strong acid (IR-120, H + ) and a weak base (IRA-743) anion-exchange resins, reducing its level to <1 ppm, without loss of lactulose. During the transglycosylation reaction of purified IWP (lactose/lactulose ratio, 1/2.4) maximum content of prebiotic compounds was achieved, i.e. 690 g kg -1 WP after 3 h of reaction. This study shows that combined chemical-enzymatic reactions together with the purification of IWP results in an efficient synthesis of prebiotic oligosaccharides. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Galacto-oligosaccharides and lactulose as protectants against desiccation of Lactobacillus delbrueckii subsp. bulcaricus.

PubMed

Santos, Mauricio I; Araujo-Andrade, Cuauhtémoc; Esparza-Ibarra, Edgar; Tymczyszyn, Elizabeth; Gómez-Zavaglia, Andrea

2014-01-01

Lactobacillus delbrueckii subsp. bulgaricus CIDCA 333 was dehydrated on desiccators containing silica gel in the presence of 20% w/w of two types of galacto-oligosaccharides (GOS Biotempo and GOS Cup Oligo H-70®) and lactulose, until no changes in water desorption were detected. After rehydration, bacterial growth was monitored at 37°C by determining: (a) the absorbance at 600 nm and (b) the near infrared spectra (NIR). Principal component analysis (PCA) was then performed on the NIR spectra of samples dehydrated in all conditions. A multiparametric flow cytometry assay was carried out using carboxyfluorescein diacetate and propidium iodide probes to determine the relative composition of damaged, viable, and dead bacteria throughout the growth kinetics. The absorbance at 600 nm and the position of the second derivative band at ∼1370 nm were plotted against the time of incubation. The efficiency of the protectants was GOS Biotempo > GOS Cup Oligo H-70®  > lactulose. The better protectant capacity of GOS Biotempo was explained on the basis of the lower contribution of damaged cells immediately after rehydration (t = 0). PCA showed three groups along PC1, corresponding to the lag, exponential and stationary phases of growth, which explained 99% of the total variance. Along PC2, two groups were observed, corresponding to damaged or viable cells. The results obtained support the use of NIR to monitor the recovery of desiccated microorganisms in real time and without the need of chemical reagents. The use of GOS and lactulose as protectants in dehydration/rehydration processes was also supported. © 2014 American Institute of Chemical Engineers.

Lactulose:Mannitol Diagnostic Test by HPLC and LC-MSMS Platforms: Considerations for Field Studies of Intestinal Barrier Function and Environmental Enteropathy

PubMed Central

Lee, Gwenyth O.; Kosek, Peter; Lima, Aldo A.M.; Singh, Ravinder; Yori, Pablo P.; Olortegui, Maribel P.; Lamsam, Jesse L.; Oliveira, Domingos B.; Guerrant, Richard L.; Kosek, Margaret

2014-01-01

ABSTRACT Objectives: The lactulose:mannitol (L:M) diagnostic test is frequently used in field studies of environmental enteropathy (EE); however, heterogeneity in test administration and disaccharide measurement has limited the comparison of results between studies and populations. We aim to assess the agreement between L:M measurement between high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD) and liquid chromatography-tandem mass spectrometry (LC-MSMS) platforms. Methods: The L:M test was administered in a cohort of Peruvian infants considered at risk for EE. A total of 100 samples were tested for lactulose and mannitol at 3 independent laboratories: 1 running an HPLC-PAD platform and 2 running LC-MSMS platforms. Agreement between the platforms was estimated. Results: The Spearman correlation between the 2 LC-MSMS platforms was high (ρ ≥ 0.89) for mannitol, lactulose, and the L:M ratio. The correlation between the HPLC-PAD platform and LC-MSMS platform was ρ = 0.95 for mannitol, ρ = 0.70 for lactulose, and ρ = 0.43 for the L:M ratio. In addition, the HPLC-PAD platform overestimated the lowest disaccharide concentrations to the greatest degree. Conclusions: Given the large analyte concentration range, the improved accuracy of LC-MSMS has important consequences for the assessment of lactulose and mannitol following oral administration in populations at risk for EE. We recommend that researchers wishing to implement a dual-sugar test as part of a study of EE use an LC-MSMS platform to optimize the accuracy of results and increase comparability between studies. PMID:24941958

Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial.

PubMed

Rahimi, Robert S; Singal, Amit G; Cuthbert, Jennifer A; Rockey, Don C

2014-11-01

Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. To compare polyethylene glycol 3350-electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related. PEG led to more rapid HE resolution than standard therapy, suggesting that

Promising Prebiotic Candidate Established by Evaluation of Lactitol, Lactulose, Raffinose, and Oligofructose for Maintenance of a Lactobacillus-Dominated Vaginal Microbiota

PubMed Central

McMillan, Amy; Seney, Shannon; van der Veer, Charlotte; Kort, Remco; Sumarah, Mark W.

2017-01-01

ABSTRACT Perturbations to the vaginal microbiota can lead to dysbiosis, including bacterial vaginosis (BV), which affects a large portion of the female population. In a healthy state, the vaginal microbiota is characterized by low diversity and colonization by Lactobacillus spp., whereas in BV, these species are displaced by a highly diverse population of bacteria associated with adverse vaginal health outcomes. Since prebiotic ingestion has been a highly effective approach to invigorate lactobacilli for improved intestinal health, we hypothesized that these compounds could stimulate lactobacilli at the expense of BV organisms to maintain vaginal health. Monocultures of commensal Lactobacillus crispatus, Lactobacillus vaginalis, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus jensenii, and Lactobacillus iners, in addition to BV-associated organisms and Candida albicans, were tested for their ability to utilize a representative group of prebiotics consisting of lactitol, lactulose, raffinose, and oligofructose. The disaccharide lactulose was found to most broadly and specifically stimulate vaginal lactobacilli, including the strongly health-associated species L. crispatus, and importantly, not to stimulate BV organisms or C. albicans. Using freshly collected vaginal samples, we showed that exposure to lactulose promoted commensal Lactobacillus growth and dominance and resulted in healthy acidity partially through lactic acid production. This provides support for further testing of lactulose to prevent dysbiosis and potentially to reduce the need for antimicrobial agents in managing vaginal health. IMPORTANCE Bacterial vaginosis (BV) and other dysbioses of the vaginal microbiota significantly affect the quality of life of millions of women. Antimicrobial therapy is often poorly effective, causes side effects, and does not prevent recurrences. We report one of very few studies that have evaluated how prebiotics—compounds that are selectively fermented

Lactulose and Lactobacillus plantarum, a Potential Complementary Synbiotic To Control Postweaning Colibacillosis in Piglets

PubMed Central

Guerra-Ordaz, A. A.; González-Ortiz, G.; La Ragione, R. M.; Woodward, M. J.; Collins, J. W.; Pérez, J. F.

2014-01-01

The potential of a prebiotic oligosaccharide lactulose, a probiotic strain of Lactobacillus plantarum, or their synbiotic combination to control postweaning colibacillosis in pigs was evaluated using an enterotoxigenic Escherichia coli (ETEC) K88 oral challenge. Seventy-two weanlings were fed four diets: a control diet (CTR), that diet supplemented with L. plantarum (2 × 1010 CFU · day−1) (LPN), that diet supplemented with 10 g · kg−1 lactulose (LAC), or a combination of the two treatments (SYN). After 7 days, the pigs were orally challenged. Six pigs per treatment were euthanized on days 6 and 10 postchallenge (PC). Inclusion of lactulose improved the average daily gain (ADG) (P < 0.05) and increased lactobacilli (P < 0.05) and the percentage of butyric acid (P < 0.02) in the colon. An increase in the ileum villous height (P < 0.05) and a reduction of the pig major acute-phase protein (Pig-MAP) in serum (P < 0.01) were observed also. The inclusion of the probiotic increased numbers of L. plantarum bacteria in the ileum and colon (P < 0.05) and in the total lactobacilli in the colon and showed a trend to reduce diarrhea (P = 0.09). The concentrations of ammonia in ileal and colonic digesta were decreased (P < 0.05), and the villous height (P < 0.01) and number of ileal goblet cells (P < 0.05) increased, at day 10 PC. A decrease in plasmatic tumor necrosis factor alpha (TNF-α) (P < 0.01) was also seen. The positive effects of the two additives were combined in the SYN treatment, resulting in a complementary synbiotic with potential to be used to control postweaning colibacillosis. PMID:24907322

Gastric emptying and orocaecal transit time of meals containing lactulose or inulin in men.

PubMed

Clegg, Miriam; Shafat, Amir

2010-08-01

The H(2) breath test is ideal for orocaecal transit time (OCTT) measurement, as it is non-invasive and inexpensive. Indigestible substrates added to a test meal are metabolised by the colonic bacteria, resulting in the production of H(2) which is detected in end-exhalation breath. However, the substrates themselves can alter the transit times in the gastrointestinal tract. The aim of the present study is to compare OCTT and gastric emptying (GE) when lactulose in liquid (L-L), solid lactulose (L-S) and solid inulin (IN-S) are added to a test meal, and subsequently, to examine if inulin alters GE. Firstly, ten male volunteers were tested on three occasions. Volunteers ate a pancake breakfast containing 100 mg of (13)C-octanoic acid and either 12 g of L-L, 12 g of L-S or 12 g of IN-S in a randomised order. Secondly, seven male volunteers were tested twice with meals containing either 12 g of IN-S or no substrate (NO-S). L-L induced the shortest OCTT (85.3 (sd 42.8) min) compared with L-S (162.4 (sd 62.6) min) and inulin (292.4 (sd 66.7) min; P = 0.007). GE half-time and lag phase (L-L: 61 (sd 9); L-S: 57 (sd 10); IN-S: 52 (sd 10) min; P = 0.005) were also affected, with L-L being the slowest. Thirdly, inulin reduced GE lag and latency phases (P < 0.05) compared with NO-S. Lactulose accelerates OCTT but delays GE compared with inulin. Inulin accelerates the onset of stomach emptying, but it has no effect on GE half-time. For these reasons, inulin is the preferred substrate for the H(2) breath test.

Treatment of faecal impaction with polyethelene glycol plus electrolytes (PGE + E) followed by a double-blind comparison of PEG + E versus lactulose as maintenance therapy.

PubMed

Candy, David C A; Edwards, Diane; Geraint, Mike

2006-07-01

To assess the efficacy of polyethylene glycol 3350 plus electrolytes (PEG + E; Movicol) as oral monotherapy in the treatment of faecal impaction in children, and to compare PEG + E with lactulose as maintenance therapy in a randomised trial. An initial open-label study of PEG + E in the inpatient treatment of faecal impaction (phase 1), followed by a randomised, double-blind comparison between PEG + E and lactulose for maintenance treatment of constipation over a 3-month period (phase 2) in children aged 2 to 11 years with a clinical diagnosis of faecal impaction. Disimpaction on PEG + E was achieved in 58 (92%) of 63 of children (89% of 2-4 year olds and 94% of 5-11 year olds) without additional interventions. A maximum dose of 4 sachets (for 2-4 year olds) or 6 sachets (for 5-11 year olds) was required; median time to disimpaction was 6 days (range, 3-7 days). Seven children (23%) reimpacted whilst taking lactulose, whereas no children reimpacted while taking PEG + E (P = 0.011). The total incidence rate of adverse events seen was higher in the lactulose group (83%) than in the PEG + E group (64%). PEG + E is safe and highly effective in the management of childhood constipation. It allows a single orally administered laxative to be used for disimpaction without recourse to invasive interventions. It is significantly more effective than lactulose as maintenance therapy, both in efficacy in treating constipation and efficacy in preventing the recurrence of faecal impaction.

Lactulose attenuates METH-induced neurotoxicity by alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum.

PubMed

Xie, Xiao-Li; He, Jie-Tao; Wang, Zheng-Tao; Xiao, Huan-Qin; Zhou, Wen-Tao; Du, Si-Hao; Xue, Ye; Wang, Qi

2018-06-01

Methamphetamine (METH) is a widely abused psychostimulant. Lactulose is a non-absorbable sugar, which effectively decreases METH-induced neurotoxicity in rat. However, the exact mechanisms need further investigation. In this study, 5-week-old male Sprague Dawley rats received METH (15 mg/kg, 8 intraperitoneal injections, 12-h interval) or saline and received lactulose (5.3 g/kg, oral gavage, 12-h interval) or vehicle 2 days prior to the METH administration. Compared to the control group, in the METH alone group, cytoplasmic vacuolar degeneration in hepatocytes, higher levels of alanine transaminase, aspartate transaminase and ammonia, overproduction of reactive oxygen species (ROS) and increase of superoxide dismutase activity in the blood were observed. Moreover, in rat striatum, expressions of nuclear factor erythroid 2-relatted factor-2 (Nrf2) and heme oxygenase-1 were suppressed in the nucleus, although over-expression of Nrf2 were observed in cytoplasm. Over-expressions of BECN1 and LC3-II indicated initiation of autophagy, while overproduction of p62 might suggest deficient autophagic vesicle turnover and impaired autophagy. Furthermore, accumulation of p62 cloud interact with Keap1 and then aggravate cytoplasmic accumulation of Nrf2. Consistently, over-expressions of cleaved caspase 3 and poly(ADP-ribose) polymerase-1 suggested the activation of apoptosis. The pretreatment with lactulose significantly decreased rat hepatic injury, suppressed hyperammonemia and ROS generation, alleviated the impaired autophagy in striatum, rescued the antioxidant system and repressed apoptosis. Taken together, with decreased blood ammonia, lactulose pretreatment reduced METH-induced neurotoxicity through alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of ingested lactulose on absorption of L-rhamnose, D-xylose, and 3-O-methyl-D-glucose in subjects with ileostomies.

PubMed

Jenkins, A P; Menzies, I S; Nukajam, W S; Creamer, B

1994-09-01

We have previously shown that small oral doses of poorly absorbed solute can significantly reduce absorption of test sugars in normal volunteers. To confirm these results and investigate the underlying mechanism, the effects of lactulose on absorption of three test sugars in subjects with ileostomies were studied. Ten fasted subjects with ileostomies ingested an isosmolar test solution containing 2.5 g 3-O-methyl-D-glucose, 5.0 g D-xylose, 1.0 g L-rhamnose, and 50 microCi 51Cr-labelled ethylenediaminetetraacetic acid together with a blue dye transit marker. Urine was collected for time periods of 0-5 h and 5-24 h, to measure excretion of absorbed sugars, and ileostomy effluent was saved from 0-5 h and from 5 h until blue dye transit marker was no longer present, to measure small-bowel output of unabsorbed sugars. After 1 week the test was repeated, including 5 g lactulose in the test solution. Inclusion of lactulose in the test solution significantly reduced the 5 h and 24 h urine excretion of L-rhamnose and D-xylose but not that of 3-O-methyl-D-glucose and increased 0- to 5-h and total ileostomy output of L-rhamnose and D-xylose but not of 3-O-methyl-D-glucose. The presence of lactulose also reduced the time for first appearance of the blue dye transit marker in the effluent and increased effluent volume together with output of electrolyte. Poorly absorbed solute reduces intestinal absorption by retention of fluid and electrolyte, with subsequent intraluminal dilution and acceleration of transit.

Lactulose Breath Test Gas Production in Childhood IBS Is Associated With Intestinal Transit and Bowel Movement Frequency.

PubMed

Chumpitazi, Bruno P; Weidler, Erica M; Shulman, Robert J

2017-04-01

In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. Children (ages 7-17 years) with pediatric Rome III IBS completed validated psychosocial questionnaires and a 2-week daily diary capturing pain and stooling characteristics. Stool form determined IBS subtype. Subjects then completed a 3-hour lactulose breath test for measurement of total breath hydrogen and methane production. Carmine red was used to determine whole intestinal transit time. A total of 87 children (mean age 13 ± 2.6 [standard deviation] years) were enrolled, of whom 50 (57.5%) were girls. All children produced hydrogen and 51 (58.6%) produced methane. Hydrogen and methane production did not correlate with either abdominal pain frequency/severity or psychosocial distress. Hydrogen and methane production did not differ significantly by IBS subtype. Methane production correlated positively with whole intestinal transit time (r = 0.31, P < 0.005) and inversely with bowel movement frequency (r = -0.245, P < 0.05). Methane production (threshold 3 ppm) as a marker for identifying IBS-C had a sensitivity of 60% and specificity of 42.9%. Lactulose breath test total methane production may serve as a biomarker of whole intestinal transit time and bowel movement frequency in children with IBS. In children with IBS, lactulose breath test hydrogen and methane production did not, however, correlate with abdominal pain, IBS subtype, or psychosocial distress.

Spectral electroencephalogram in liver cirrhosis with minimal hepatic encephalopathy before and after lactulose therapy.

PubMed

Singh, Jatinderpal; Sharma, Barjesh Chander; Maharshi, Sudhir; Puri, Vinod; Srivastava, Siddharth

2016-06-01

Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy. Spectral electroencephalogram (sEEG) analysis improves the recognition of MHE by decreasing inter-operator variability and providing quantitative parameters of brain dysfunction. We compared sEEG in patients with cirrhosis with and without MHE and the effects of lactulose on sEEG in patients with MHE. One hundred patients with cirrhosis (50 with and 50 without MHE) were enrolled. Diagnosis of MHE was based on psychometric hepatic encephalopathy score (PHES) of ≤ -5. Critical flicker frequency, model of end-stage liver disease score, and sEEG were performed at baseline in all patients. The spectral variables considered were the mean dominant frequency (MDF) and relative power in beta, alpha, theta, and delta bands. Patients with MHE were given 3 months of lactulose, and all parameters were repeated. Spectral electroencephalogram analysis showed lower MDF (7.8 ± 1.7 vs 8.7 ± 1.3 Hz, P < 0.05) and higher theta relative power (34.29 ± 4.8 vs 24 ± 6.7%, P = 001) while lower alpha relative power (28.6 ± 4.0 vs 33.5 ± 5.3%, P = .001) in patients with MHE than in patients without MHE. With theta relative power, sensitivity 96%, specificity 84%, and accuracy of 90% were obtained for diagnosis of MHE. After lactulose treatment, MHE improved in 21 patients, and significant changes were seen in MDF (7.8 ± 0.5 vs 8.5 ± 0.6), theta (34.2 ± 4.8 vs 23.3 ± 4.1%), alpha (28.6 ± 4.0 vs 35.5 ± 4.5%), and delta relative power (13.7 ± 3.5 vs 17.0 ± 3.3%) after treatment (P ≤ 0.05). Spectral EEG is a useful objective and quantitative tool for diagnosis and to assess the response to treatment in patients with cirrhosis with MHE. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort.

PubMed

Lee, Gwenyth O; McCormick, Benjamin J J; Seidman, Jessica C; Kosek, Margaret N; Haque, Rashidul; Olortegui, Maribel Paredes; Lima, Aldo A M; Bhutta, Zulfiqar A; Kang, Gagandeep; Samie, Amidou; Amour, Caroline; Mason, Carl J; Ahmed, Tahmeed; Yori, Pablo Peñataro; Oliveira, Domingos B; Alam, Didar; Babji, Sudhir; Bessong, Pascal; Mduma, Estomih; Shrestha, Sanjaya K; Ambikapathi, Ramya; Lang, Dennis R; Gottlieb, Michael; Guerrant, Richard L; Caulfield, Laura E; For The Mal-Ed Network Investigators

2017-07-01

The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function.

Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort

PubMed Central

Lee, Gwenyth O.; McCormick, Benjamin J. J.; Seidman, Jessica C.; Kosek, Margaret N.; Haque, Rashidul; Olortegui, Maribel Paredes; Lima, Aldo A. M.; Bhutta, Zulfiqar A.; Kang, Gagandeep; Samie, Amidou; Amour, Caroline; Mason, Carl J.; Ahmed, Tahmeed; Yori, Pablo Peñataro; Oliveira, Domingos B.; Alam, Didar; Babji, Sudhir; Bessong, Pascal; Mduma, Estomih; Shrestha, Sanjaya K.; Ambikapathi, Ramya; Lang, Dennis R.; Gottlieb, Michael; Guerrant, Richard L.; Caulfield, Laura E.

2017-01-01

Abstract. The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function. PMID:28719336

Contribution to the production of lactulose-rich whey by in situ electro-isomerization of lactose and effect on whey proteins after electro-activation as confirmed by matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

PubMed

Kareb, Ourdia; Champagne, Claude P; Aïder, Mohammed

2016-04-01

Cheese-whey, a major co-product of the dairy industry, has recently been the subject of many technological applications. We studied the bioconversion of whey into valuable bio-products such as a potential lactulose prebiotic and compounds with antioxidant properties. This paper examines efficiency, safety, and economics of electro-activation as an eco-friendly technology for a maximum valorization of whey. Thus, a bottom-up approach was therefore addressed. The effect of 4 experimental parameters--low working temperatures (0, 10, and 25 °C), current intensities (400, 600, and 800 mA), volume conditions (100, 200, and 300 mL), and feed concentrations [7, 14, and 28% (wt/vol)]--on lactose-whey isomerization to lactulose under electro-activation process were studied. Structural characteristics of whey proteins and antioxidant functionality were also investigated. The results showed a compromise to be reached between both parameters. Therefore, the maximum yield of 35% of lactulose was achieved after 40 min of reaction at the working temperature of 10 °C under 400 mA electric current field and 100-mL volume conditions with using feed solution at 7% (wt/vol). The isomerization of lactose to lactulose is accomplished by subsequent degradation to galactose, but only at a very small amount. Additionally, whey electro-activation showed significantly elevated antioxidant capacity compared with the untreated samples. The enhancement of antioxidant functionality of whey electro-activation resulted from the synergistic effect of its partial hydrolysis and the formation of antioxidant components that were able to scavenge free radicals. In conclusion, the findings of this study reveal that the whey treated by the safety electro-activation technology has both lactulose-prebiotic and antioxidant properties and could have a substantial application in the manufacture of pharmaceutical and functional foods. Copyright © 2016 American Dairy Science Association. Published by Elsevier

Assessment of the Effect of Intestinal Permeability Probes (Lactulose And Mannitol) and Other Liquids on Digesta Residence Times in Various Segments of the Gut Determined by Wireless Motility Capsule: A Randomised Controlled Trial.

PubMed

Sequeira, Ivana R; Lentle, Roger G; Kruger, Marlena C; Hurst, Roger D

2015-01-01

Whilst the use of the mannitol/lactulose test for intestinal permeability has been long established it is not known whether the doses of these sugars modify transit time Similarly it is not known whether substances such as aspirin that are known to increase intestinal permeability to lactulose and mannitol and those such as ascorbic acid which are stated to be beneficial to gastrointestinal health also influence intestinal transit time. Gastric and intestinal transit times were determined with a SmartPill following consumption of either a lactulose mannitol solution, a solution containing 600 mg aspirin, a solution containing 500 mg of ascorbic acid or an extract of blackcurrant, and compared by doubly repeated measures ANOVA with those following consumption of the same volume of a control in a cross-over study in six healthy female volunteers. The dominant frequencies of cyclic variations in gastric pressure recorded by the Smartpill were determined by fast Fourier transforms. The gastric transit times of lactulose mannitol solutions, of aspirin solutions and of blackcurrant juice did not differ from those of the control. The gastric transit times of the ascorbic acid solutions were significantly shorter than those of the other solutions. There were no significant differences between the various solutions either in the total small intestinal or colonic transit times. The intraluminal pHs during the initial quartiles of the small intestinal transit times were lower than those in the succeeding quartiles. This pattern did not vary with the solution that was consumed. The power of the frequencies of cyclic variation in intragastric pressure recorded by the Smartpill declined exponentially with increase in frequency and did not peak at the reported physiological frequencies of gastric contractile activity. Whilst the segmental residence times were broadly similar to those using other methods, the high degree of variation between subjects generally precluded the

Effect of ageing on the gastro-intestinal transit of a lactulose-supplemented mixed solid-liquid meal in humans.

PubMed

Wegener, M; Börsch, G; Schaffstein, J; Lüth, I; Rickels, R; Ricken, D

1988-01-01

Gastro-intestinal transit of a mixed solid-liquid meal containing wheat bread, scrambled eggs, coffee labelled with 99mTc, orange juice with lactulose and indigocarmine was evaluated in 21 young control (mean age 33.5 years) and 25 elderly subjects (mean age 81.7 years) without gastrointestinal complaints or severe medical illness. The rate of gastric emptying was determined by an anterior gamma camera technique, mouth-to-caecum transit by the hydrogen breath test and whole-gut transit by the first stool passage of indigocarmine. Gastric emptying was significantly prolonged in older subjects: t1/2 = 136 +/- (SEM) 13 versus 81 +/- 4 min; p less than 0.001. Concerning mouth-to-caecum or whole-gut transit time, significant differences between the two study groups were not detected.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

PubMed

Ruston, Teresa; Hunter, Kathleen; Cummings, Greta; Lazarescu, Adriana

2013-01-01

Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

Association between Symptoms of Irritable Bowel Syndrome and Methane and Hydrogen on Lactulose Breath Test

PubMed Central

Lee, Kang Nyeong; Koh, Dong Hee; Sohn, Won; Lee, Sang Pyo; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon; Hahm, Joon Soo

2013-01-01

Whether hydrogen and methane gas produced during lactulose breath test (LBT) are associated with symptoms of irritable bowel syndrome (IBS) is not determined. We aimed to investigate whether hydrogen and methane on LBT are associated with IBS symptoms. Sixty-eight IBS patients meeting the Rome III criteria for IBS, and 55 healthy controls, underwent LBT. The IBS subjects recorded their customary gastrointestinal symptoms on a questionnaire using visual analogue scales. LBT positivity was defined to be above 20 ppm rise of hydrogen or 10 ppm rise of methane within 90 min. Gas amounts produced during LBT were determined by calculating area under the curve of hydrogen and methane excretion. Symptom severity scores were not different between the LBT (+) IBS and LBT (-) IBS subjects and also between methane producers and non-methane producers. Gas amounts produced during LBT were not associated with IBS symptoms, except a weak correlation between total gas amounts and a few IBS symptoms such as bloating (r = 0.324, P = 0.039), flatulence (r = 0.314, P = 0.046) and abdominal pain (r = 0.364, P = 0.018) only in LBT (+) IBS. In conclusion, hydrogen and methane gas on LBT are not useful for predicting the customary symptoms and subtypes of IBS. PMID:23772156

A clinical hepatologist's predictions about non-absorbed carbohydrates for the early twenty-first century.

PubMed

Conn, H O

1997-01-01

To put these predictions into perspective, the primary indication for lactulose therapy in the treatment of HE and SHE is presented and discussed. Six secondary indications for lactulose therapy are also listed and briefly commented upon. A dozen predictions about the status of lactulose are presented and briefly discussed. A. Lactulose will be the treatment of choice for HE.B. TIPS will be the most common cause of HE.C. Lactulose will not be approved in Mexico. D. Lactulose plus anti-diarrheal drugs will be agents for treatment of HE. E. Lactulose will not be the treatment of choice for constipation. F. Lactulose will not be used for Salmonella or Shigella carrier states. G. Lactulose will be routinely administered prophylactically after TIPS. H. Lactulose will be administered prophylactically to cirrhotic patients with portal hypertension. I. Lactulose plus anti-diarrheal drugs will be used for a variety of diverse purposes: (i) Suppression of bacterial growth; (ii) prevention of bacteriuria; (iii) diminution of cholesterol saturation of bile; (iv) adjunct treatment of gallstones with ursodeoxycholic acid; (v) Prevention of colon carcinoma.

Determination of rifaximin treatment period according to lactulose breath test values in nonconstipated irritable bowel syndrome subjects.

PubMed

Bae, Suhyun; Lee, Kwang Jae; Kim, Young-Sang; Kim, Kyu-Nam

2015-06-01

Small intestinal bacterial overgrowth (SIBO) can partly explain irritable bowel syndrome (IBS), and rifaximin has been observed to improve abdominal symptoms in nonconstipated IBS patients. However, there are few reports on the association of the rifaximin treatment periods with the results of a lactulose breath test (LBT). Therefore, we performed a retrospective review of patient charts to investigate the relation between the rifaximin treatment periods with LBT results in nonconstipated IBS patients. We also evaluated the time to achieve a symptomatic improvement in the IBS patients as compared to the changes in the LBT. We reviewed the charts for patients who showed IBS symptoms with documented positive results for LBT during their initial visit and who had a follow-up LBT after treatment with rifaximin. The LBT values were compared to the subjects' symptom scores. A total of 102 subjects had a follow-up LBT to assess LBT normalization. The subjects were divided into groups according to treatment periods of 4 weeks (n = 36), 8 weeks (n = 43), and 12 weeks (n = 23). The groups with a longer treatment exhibited an increase in the hydrogen gas value at 90 min and its sum during 90 min at the initial LBT. There were significant differences in hydrogen gas value at 90 min and in its sum during 90 min at the initial LBT between the groups treated for 4 and 12 weeks. The most significant treatment response was observed during the first 4 weeks for all treatment groups. Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO.

Lactulose

MedlinePlus

... of patients with liver disease. It works by drawing ammonia from the blood into the colon where ... in, tightly closed, and out of reach of children. Store it at room temperature and away from ...

A Randomized Clinical Trial on Treatment of Chronic Constipation by Traditional Persian Medicine Recommendations Compared to Allopathic Medicine: A Pilot Study

PubMed Central

Fattahi, Mohammad Reza; Alorizi, Seyed Morteza Emami; Nimrouzi, Majid; Zarshenas, Mohammad M.; Parvizi, Mohammad Mahdi

2017-01-01

Background: The aim of this study was to compare the efficacy and side effects of lactulose plus traditional Persian medicine with only lactulose on the functional chronic constipation. Methods: Participants included 20 patients (10 in each group) aged 18–80 years, with major inclusion criteria of ROME III. They were assigned into two parallel therapeutic groups, including the intervention group (lactulose plus traditional Persian medicine [TPM] advices) and control group (only lactulose) through a block randomization. Weekly follow-up was done for 1 month for both groups. Results: After the intervention, the frequency of bowel habit increased significantly in patients of both groups (P = 0.001), and the frequency of hard stool defecation, sensation of painful defecation, sensation of incomplete evacuation, sensation of anorectal obstruction, and manual maneuver for evacuation were decreased significantly in patients of both groups (P < 0.001 for all comparisons and 0.025 for manual maneuver). However, the only significant difference between the two groups was more reduction in the sensation of painful defecation in the lactulose group versus lactulose plus TPM advices (P = 0.014). Conclusions: Based on the pilot study, no significant difference was shown between TPM with lactulose and lactulose only in the management of chronic functional constipation. However, the easy recommendations of TPM can be useful in improving chronic constipation. PMID:28757927

Effect of the herbal medicine Dai-kenchu-to for serum ammonia in hepatectomized patients.

PubMed

Kaiho, Takashi; Tanaka, Toshikazu; Tsuchiya, Shunichi; Yanagisawa, Shnji; Takeuchi, Osamu; Miura, Masami; Saigusa, Naoki; Miyazaki, Masaru

2005-01-01

Prolonged paralytic ileus occurring in hepatectomized patients may induce hyperammonemia or bacterial translocation, which injures the remnant liver function and sometimes causes post-resection liver failure. We examined the effectiveness of the herbal medicine, Dai-kenchu-to (DKT), on postoperative serum ammonia levels in patients with liver resection and compared it with lactulose. Patients with liver resection were divided into three groups. Lactulose group (n=31), 16g of lactulose was administered orally three times a day from the first postoperative day. DKT group (n=27), 5g of DKT was administered in the same fashion. Control group (n=26), neither lactulose nor DKT was administered. In all three groups, 16g of lactulose was administered three times a day for three days preoperatively. There was no significant difference among the groups in age, gender and preoperative hepatic functional values, such as ICG-R15 or galactose tolerance test. There was also no difference in parenchymal hepatic resection rate, operative time and amount of intraoperative bleeding volume. Postoperative serum ammonia levels were significantly lower in the DKT group than control and lactulose groups. Instances of delayed flatulence and occurrence of diarrhea were also fewer in the DKT group. DKT may become a more effective and safe agent than lactulose in postoperative management of liver resection.

Effect and safety of deep needling and shallow needling for functional constipation: a multicenter, randomized controlled trial.

PubMed

Wu, Jiani; Liu, Baoyan; Li, Ning; Sun, Jianhua; Wang, Lingling; Wang, Liping; Cai, Yuying; Ye, Yongming; Liu, Jun; Wang, Yang; Liu, Zhishun

2014-12-01

Aupuncture is widely used for functional constipation. Effect of acupuncture might be related to the depth of needling; however, the evidence is limited. This trial aimed to evaluate the effect and safety of deep needling and shallow needling for functional constipation, and to assess if the deep needling and shallow needling are superior to lactulose. We conducted a prospective, superiority-design, 5-center, 3-arm randomized controlled trial. A total of 475 patients with functional constipation were randomized to the deep needling group (237), shallow needling group (119), and lactulose-controlled group (119) in a ratio of 2:1:1. Sessions lasted 30 minutes each time and took place 5 times a week for 4 weeks in 2 acupuncture groups. Participants in the lactulose group took lactulose orally for 16 continuous weeks. The primary outcome was the change from baseline of mean weekly spontaneous bowel movements (SBMs) during week 1 to 4 (changes from the baselines of the weekly SBMs at week 8 and week 16 in follow-up period were also assessed simultaneously). Secondary outcomes were the weekly SBMs of each assessing week, the mean score change from the baseline of constipation-related symptoms over week 1 to 4, and the time to the first SBM. Emergency drug usage and adverse effects were monitored throughout the study.SBMs and constipation-related symptoms were all improved in the 3 groups compared with baseline at each time frame (P<0.01, all). The changes in the mean weekly SBMs over week 1 to 4 were 2 (1.75) in the deep needling group, 2 (1.75) in the shallow needling group, and 2 (2) in the lactulose group (P>0.05, both compared with the lactulose group). The changes of mean weekly SBMs at week 8 and week 16 in the follow-up period were 2 (2), 2 (2.5) in the deep needling group, 2 (3), 1.5 (2.5) in the shallow needling group, and 1 (2), 1 (2) in the lactulose group (P<0.05, all compared with the lactulose group). No significant difference was observed among the 3

Effect and Safety of Deep Needling and Shallow Needling for Functional Constipation

PubMed Central

Wu, Jiani; Liu, Baoyan; Li, Ning; Sun, Jianhua; Wang, Lingling; Wang, Liping; Cai, Yuying; Ye, Yongming; Liu, Jun; Wang, Yang; Liu, Zhishun

2014-01-01

Abstract Aupuncture is widely used for functional constipation. Effect of acupuncture might be related to the depth of needling; however, the evidence is limited. This trial aimed to evaluate the effect and safety of deep needling and shallow needling for functional constipation, and to assess if the deep needling and shallow needling are superior to lactulose. We conducted a prospective, superiority-design, 5-center, 3-arm randomized controlled trial. A total of 475 patients with functional constipation were randomized to the deep needling group (237), shallow needling group (119), and lactulose-controlled group (119) in a ratio of 2:1:1. Sessions lasted 30 minutes each time and took place 5 times a week for 4 weeks in 2 acupuncture groups. Participants in the lactulose group took lactulose orally for 16 continuous weeks. The primary outcome was the change from baseline of mean weekly spontaneous bowel movements (SBMs) during week 1 to 4 (changes from the baselines of the weekly SBMs at week 8 and week 16 in follow-up period were also assessed simultaneously). Secondary outcomes were the weekly SBMs of each assessing week, the mean score change from the baseline of constipation-related symptoms over week 1 to 4, and the time to the first SBM. Emergency drug usage and adverse effects were monitored throughout the study. SBMs and constipation-related symptoms were all improved in the 3 groups compared with baseline at each time frame (P < 0.01, all). The changes in the mean weekly SBMs over week 1 to 4 were 2 (1.75) in the deep needling group, 2 (1.75) in the shallow needling group, and 2 (2) in the lactulose group (P > 0.05, both compared with the lactulose group). The changes of mean weekly SBMs at week 8 and week 16 in the follow-up period were 2 (2), 2 (2.5) in the deep needling group, 2 (3), 1.5 (2.5) in the shallow needling group, and 1 (2), 1 (2) in the lactulose group (P < 0.05, all compared with the lactulose group). No significant difference

NMR-based urinary profiling of lactulose/mannitol ratio used to assess the altered intestinal permeability in acute on chronic liver failure (ACLF) patients.

PubMed

Kumar, Dinesh; Pandey, Gaurav; Bansal, Deepak; Rawat, Atul; Kumar, Umesh; Dubey, Durgesh; Guleria, Anupam; Saraswat, Vivek Anand

2017-04-01

The article presents a simplified NMR-based protocol for urinary profiling of lactulose/mannitol ratio (LMR) and demonstrates here its utility to assess increased intestinal permeability (IP) in patients with acute on chronic liver failure (ACLF). ACLF is a serious clinical complication associated with chronic liver disease (cirrhosis). The major risk factor in its development is increased IP ('leaky gut'), which has been linked to disease progression and to infectious complications. However, IP has seldom been investigated in patients with ACLF, even though patients frequently report gastrointestinal disorders and associated complications. To this end, we first optimized the NMR-based targeted profiling of urinary metabolites (i.e. actulose, mannitol, and creatinine) and subsequently used this resulted protocol (a) first to evaluate the altered IP in ACLF patients and then (b) to explore its utility for monitoring the treatment response in these patients. The normal profiles were obtained for 7 age and sex matched healthy volunteers. The results revealed that the urinary LMR excretion was significantly higher in ACLF patients compared to normal controls (median ~0.7, range (0.12-2.84), vs median ~0.11, range (0.02-0.28), p < 0.001) suggesting that the ACLF patients' exhibit altered IP. However, the LMR excretion in six clinically improved follow-up ACLF patients was comparable to normal controls indicating restored IP after the treatment. The protocol-as demonstrated here with ACLF-is equally applicable for evaluating IP or mucosal barrier function in other intestinal disorders with reasonable sensitivity and specificity, highlighting its general utility. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Intestinal Microbiota Ecological Response to Oral Administrations of Hydrogen-Rich Water and Lactulose in Female Piglets Fed a Fusarium Toxin-Contaminated Diet.

PubMed

Zheng, Weijiang; Ji, Xu; Zhang, Qing; Yao, Wen

2018-06-16

The objective of the current experiment was to explore the intestinal microbiota ecological response to oral administrations of hydrogen-rich water (HRW) and lactulose (LAC) in female piglets fed a Fusarium mycotoxin-contaminated diet. A total of 24 individually-housed female piglets (Landrace × large × white; initial average body weight, 7.25 ± 1.02 kg) were randomly assigned to receive four treatments (six pigs/treatment): uncontaminated basal diet (negative control, NC), mycotoxin-contaminated diet (MC), MC diet + HRW (MC + HRW), and MC diet + LAC (MC + LAC) for 25 days. Hydrogen levels in the mucosa of different intestine segments were measured at the end of the experiment. Fecal scoring and diarrhea rate were recorded every day during the whole period of the experiment. Short-chain fatty acids (SCFAs) profiles in the digesta of the foregut and hindgut samples were assayed. The populations of selected bacteria and denaturing gradient gel electrophoresis (DGGE) profiles of total bacteria and methanogenic Archaea were also evaluated. Results showed that Fusarium mycotoxins not only reduced the hydrogen levels in the caecum but also shifted the SCFAs production, and populations and communities of microbiota. HRW treatment increased the hydrogen levels of the stomach and duodenum. HRW and LAC groups also had higher colon and caecum hydrogen levels than the MC group. Both HRW and LAC protected against the mycotoxin-contaminated diet-induced higher diarrhea rate and lower SCFA production in the digesta of the colon and caecum. In addition, the DGGE profile results indicated that HRW and LAC might shift the pathways of hydrogen-utilization bacteria, and change the diversity of intestine microbiota. Moreover, HRW and LAC administrations reversed the mycotoxin-contaminated diet-induced changing of the populations of Escherichia coli (E. coli) and Bifidobacterium in ileum digesta and hydrogen-utilizing bacteria in colon digesta.

Resolution of common dietary sugars from probe sugars for test of intestinal permeability using capillary column gas chromatography.

PubMed

Farhadi, Ashkan; Keshavarzian, Ali; Fields, Jeremy Z; Sheikh, Maliha; Banan, Ali

2006-05-19

The most widely accepted method for the evaluation of intestinal barrier integrity is the measurement of the permeation of sugar probes following an oral test dose of sugars. The most-widely used sugar probes are sucrose, lactulose, mannitol and sucralose. Measuring these sugars using a sensitive gas chromatographic (GC) method, we noticed interference on the area of the lactulose and mannitol peaks. We tested different sugars to detect the possible makeup of these interferences and finally detected that the lactose interferes with lactulose peak and fructose interferes with mannitol peak. On further developing of our method, we were able to reasonably separate these peaks using different columns and condition for our assay. Sample preparation was rapid and simple and included adding internal standard sugars, derivitization and silylation. We used two chromatographic methods. In the first method we used Megabore column and had a run time of 34 min. This resulted in partial separation of the peaks. In the second method we used thin capillary column and was able to reasonably separate the lactose and lactulose peaks and the mannitol and fructose peaks with run time of 22 min. The sugar probes including mannitol, sucrose, lactulose, sucralose, fructose and lactose were detected precisely, without interference. The assay was linear between lactulose concentrations of 0.5 and 40 g/L (r(2)=1.000, P<0.0001) and mannitol concentrations of 0.01 and 40 g/L (r(2)=1.000). The sensitivity of this method remained high using new column and assay condition. The minimum detectable concentration calculated for both methods was 0.5 mg/L for lactulose and 1 mg/L for mannitol. This is the first report of interference of commonly used sugars with test of intestinal permeability. These sugars are found in most of fruits and dairy products and could easily interfere with the result of permeability tests. Our new GC assay of urine sugar probes permits the simultaneous quantitation of

Improving Properties of a Novel β-Galactosidase from Lactobacillus plantarum by Covalent Immobilization.

PubMed

Benavente, Rocio; Pessela, Benevides C; Curiel, Jose Antonio; de las Rivas, Blanca; Muñoz, Rosario; Guisán, Jose Manuel; Mancheño, Jose M; Cardelle-Cobas, Alejandra; Ruiz-Matute, Ana I; Corzo, Nieves

2015-04-30

A novel β-galactosidase from Lactobacillus plantarum (LPG) was over-expressed in E. coli and purified via a single chromatographic step by using lowly activated IMAC (immobilized metal for affinity chromatography) supports. The pure enzyme exhibited a high hydrolytic activity of 491 IU/mL towards o-nitrophenyl β-D-galactopyranoside. This value was conserved in the presence of different divalent cations and was quite resistant to the inhibition effects of different carbohydrates. The pure multimeric enzyme was stabilized by multipoint and multisubunit covalent attachment on glyoxyl-agarose. The glyoxyl-LPG immobilized preparation was over 20-fold more stable than the soluble enzyme or the one-point CNBr-LPG immobilized preparation at 50 °C. This β-galactosidase was successfully used in the hydrolysis of lactose and lactulose and formation of different oligosaccharides was detected. High production of galacto-oligosaccharides (35%) and oligosaccharides derived from lactulose (30%) was found and, for the first time, a new oligosaccharide derived from lactulose, tentatively identified as 3'-galactosyl lactulose, has been described.

Systematic Review of the Economic Burden of Overt Hepatic Encephalopathy and Pharmacoeconomic Impact of Rifaximin.

PubMed

Neff, Guy; Iii, Woodie Zachry

2018-04-12

Hepatic encephalopathy (HE), a common neurologic complication in cirrhosis, is associated with substantial disease and economic burden. Rifaximin is a non-systemic antibiotic that reduces the risk of overt HE recurrence and overt HE-related hospitalizations. Our objective was to provide an overview of the direct HE-related costs and cost benefits of rifaximin, lactulose, and rifaximin plus lactulose. A systematic review of PubMed and relevant meeting abstracts was conducted to identify publications since 1 January 2007 reporting economic data related to HE and rifaximin and/or lactulose. Further, a public database and published literature were used to estimate current costs of hospitalization for overt HE, and potential cost savings of HE-related hospitalizations with rifaximin. The methodological quality of included studies was evaluated using the Drummond checklist. A total of 16 reports were identified for inclusion in the systematic review. Globally, HE-related direct costs ranged from $US5370 to $US50,120 annually per patient. Rifaximin was associated with shorter hospital stays and reduced healthcare costs. Rifaximin also has the potential to reduce overt HE-related hospitalization risk by 50% compared with lactulose. Rifaximin was shown to have a favourable pharmacoeconomic profile compared with lactulose (based on the incremental cost-effectiveness ratio). In addition to its clinical benefits (e.g. reduction in the risk of recurrence of overt HE, overt HE-related hospitalizations, favourable adverse event profile), economic data are favourable for the use of rifaximin in patients with a history of overt HE.

The LUCK study: Laxative Usage in patients with GP-diagnosed Constipation in the UK, within the general population and in pregnancy. An epidemiological study using the General Practice Research Database (GPRD)

PubMed Central

Shafe, Anna C. E.; Lee, Sally; Dalrymple, Jamie S. O.; Whorwell, Peter J.

2011-01-01

Background: Despite the high prevalence of constipation and its related public health implications, there is relatively little research available on the condition from large epidemiological studies. The aim of this study was to investigate the epidemiology of general practitioner (GP)-diagnosed constipation and the prescribing trends for laxatives in the UK, within the general population and during pregnancy. Methods: A cohort study for the period from 2005 to 2009 was performed using the UK primary care database (General Practice Research Database), which contains information on over 3 million individuals. Results: The prevalence of GP-diagnosed constipation ranged from 12 per 1000 persons in 2005 (0.012 per person year) to 12.8 per 1000 in 2009 (0.013 per person year). The prevalence was almost twice as high in women as in men, and was higher in older patients. In 2005 the most commonly prescribed laxatives were lactulose (37%), senna (26%), macrogol (19%), ispaghula (6%), docusate sodium (5%), bisacodyl (4%) and glycerol suppositories (2%). By 2009, this pattern had changed: macrogol (31%), lactulose (29%), senna (22%), ispaghula (5%), docusate sodium (6%), bisacodyl (3%) and glycerol suppositories (3%). In pregnancy, lactulose accounted for 81% of laxative use in 2005, falling to 64% by 2009. In contrast, macrogol use in pregnancy rose from 13% in 2005 to 32% in 2009. Conclusions: GP-diagnosed constipation is common, accounting for a large number of consultations. Laxative prescribing trends have changed over the 5-year study period, prescriptions for macrogol becoming increasingly common and prescriptions for lactulose and senna less common. Macrogol also appears to have been replacing lactulose for treating constipation in pregnant women. PMID:22043228

Evaluation of differential disaccharide excretion in urine for non-invasive investigation of altered intestinal disaccharidase activity caused by alpha-glucosidase inhibition, primary hypolactasia, and coeliac disease.

PubMed Central

Bjarnason, I; Batt, R; Catt, S; Macpherson, A; Maxton, D; Menzies, I S

1996-01-01

BACKGROUND/AIM: The reliability of a quantitative method for the non-invasive assessment of intestinal disaccharide hydrolysis was assessed. METHODS: Differential excretion of intact disaccharide, expressed as ratios of lactulose to appropriate hydrolysable disaccharides in urine collected following combined ingestion, has been investigated in healthy volunteers with drug induced alpha-glucosidase inhibition, in subjects with primary hypolactasia, and patients with coeliac disease. RESULTS: Oral administration of the alpha-glucosidase inhibitor 'Acarbose' (BAY g 5421, 200 mg) together with sucrose and lactulose increased the urinary sucrose/lactulose excretion ratios (% dose/10 h) fivefold. The effect was quantitatively reproducible, a higher dose of 'Acarbose' (500 mg) increasing the excretion ratio to about 1.0 indicating complete inhibition of intestinal sucrase activity. The suitability of the method for measuring differences in dose/response and duration of action was assessed by comparing three different alpha-glucosidase inhibitors (BAY g 5421, BAY m 1099, and BAY o 1248) and found to be satisfactory. Subjects with primary adult hypolactasia had urine lactose/lactulose excretion ratios raised to values indicating reduced rather than complete absence of lactase activity whereas sucrose/lactulose ratios were not significantly affected. 'Whole' intestinal disaccharidase activity assessed by this method demonstrated impairment of lactase, sucrase, and isomaltase in eight, one, and seven, respectively, of 20 patients with coeliac disease. By contrast in vitro assay of jejunal biopsy tissue indicated pan-disaccharidase deficiency in all but five of these patients. This shows the importance of distinguishing between 'local' and 'whole' intestinal performance. CONCLUSIONS: Differential urinary excretion of ingested disaccharides provides a reliable, quantitative, and non-invasive technique for assessing profiles of intestinal disaccharidase activity. PMID:8949640

Dietary raw versus retrograded resistant starch enhances apparent but not true magnesium absorption in rats.

PubMed

Heijnen, M L; van den Berg, G J; Beynen, A C

1996-09-01

Dietary raw (RS2) vs. retrograded resistant starch (RS3) raises apparent magnesium absorption in rats. The mechanism proposed is that RS2 enhances magnesium avaibility for absorption; it does this by increasing ileal solubility of magnesium due to a reduction in pH as a consequence of RS2 fermentation in the gut. The mechanism implies that dietary RS2 vs. RS3 would raise true magnesium absorption and stimulate reabsorption of endogenous magnesium, leading to a lower fecal excretion of endogenous magnesium. Dietary lactulose vs. glucose raises apparent magnesium absorption, and the mechanism proposed is similar to that for the stimulatory effect of RS2 vs. RS3. Thus, we measured in rats fed RS3, RS2, glucose or lactulose true magnesium absorption on the basis of the retention of the orally and intraperitoneally administered radiotracer 28Mg. Feeding rats RS2 instead of RS3 significantly enhanced apparent but not true magnesium absorption, because RS2 lowered fecal excretion of endogenous magnesium. When compared with dietary glucose, lactulose significantly raised both apparent and true magnesium absorption, but did not affect fecal excretion of endogenous magnesium. It is suggested that the proposed mechanism by which RS2 and lactulose would enhance magnesium absorption is disproved by the present data.

The effect of poorly absorbed solute on intestinal absorption.

PubMed

Menzies, I S; Jenkins, A P; Heduan, E; Catt, S D; Segal, M B; Creamer, B

1990-12-01

To determine the effects of poorly absorbed solute on intestinal absorption, the urinary recovery of ingested lactulose, L-rhamnose, D-xylose, and 3-O-methyl-D-glucose was measured after simultaneous ingestion of various 'loads' of mannitol given in iso-osmolar solution. Mannitol reduced intestinal uptake of the poorly absorbed test sugars, lactulose and L-rhamnose; uptake of D-xylose and 3-O-methyl-D-glucose, which are absorbed by carrier-mediated transport largely from the jejunum, was less affected. The dose-response effect of mannitol on the absorption of L-rhamnose was approximately exponential; doses of 5, 10, and 20 g mannitol reduced the average urinary excretion of L-rhamnose by 34.7%, 51.7%, and 61.2%, respectively. In this respect, an osmotically equivalent load of lactulose, ingested as 'solute', was approximately twice as effective as mannitol in reducing L-rhamnose absorption, probably because lactulose is more poorly absorbed than mannitol (less than 1.0% versus 32-41%). Ingestion of other poorly absorbed solutes such as raffinose, sorbitol, xylitol, magnesium sulphate, and sodium sulphate also significantly depressed the absorption of L-rhamnose; in contrast, more efficiently absorbed solutes, such as sodium chloride, glucose, glycerol, and urea had little effect.

A study of the methodological and clinical validity of the combined lactulose hydrogen breath test with scintigraphic oro-cecal transit test for diagnosing small intestinal bacterial overgrowth in IBS patients.

PubMed

Zhao, J; Zheng, X; Chu, H; Zhao, J; Cong, Y; Fried, M; Fox, M; Dai, N

2014-06-01

Small intestinal bacterial overgrowth (SIBO) may be a cause of irritable bowel syndrome (IBS); however, current investigations have important limitations. We aimed to identify clinically relevant diagnostic criteria for SIBO based on lactulose hydrogen breath test (LHBT) alone and combined with scintigraphic measurement of oro-cecal transit (SOCT). Results of LHBT/SOCT investigation from 89 IBS patients and 13 healthy volunteers were included in a systematic analysis of six published criteria for SIBO diagnosis. Clinical relevance of competing criteria was determined by assessing (i) prevalence of SIBO in IBS patients and healthy volunteers (ii) if SIBO diagnosis predicted improvement in IBS symptoms in a prospective, pilot therapeutic trial of a non-absorbable antibiotic (rifaximin 600 mg b.d.) in IBS patients. Reproducibility of SIBO diagnosis by combined LHBT/SOCT was near perfect. A ≥5 ppm H2 increase prior to appearance of cecal contrast was detected in more IBS patients than healthy volunteers (35/89 vs 1/13; p = 0.026), but not for other diagnostic criteria. IBS patients with SIBO, compared to those without SIBO, reported significantly greater improvement in abdominal symptoms following rifaximin therapy (p < 0.002 overall IBS symptom severity). This improvement was most marked in D-IBS patients in whom all symptoms improved, including stool frequency and consistency (all p < 0.004). Combined LHBT/SOCT testing using a H2 5 ppm cutoff may identify a subgroup of IBS patients with SIBO. Pilot data examining the clinical response to rifaximin suggest that this subset of IBS patients may benefit more than those with a normal test. © 2014 John Wiley & Sons Ltd.

Transgalactosylation and hydrolytic activities of commercial preparations of β-galactosidase for the synthesis of prebiotic carbohydrates.

PubMed

Guerrero, Cecilia; Vera, Carlos; Conejeros, Raúl; Illanes, Andrés

2015-03-01

β-Galactosidases exhibit both hydrolytic and transgalactosylation activities; the former has been used traditionally for the production of delactosed milk and dairies, while the latter is being increasingly used for the synthesis of lactose-derived oligosaccharides: balance between both activities was highly dependent on the enzyme origin: β-galactosidases from Aspegillus oryzae and Bacillus circulans exhibited high transgalactosylation activity, while those from one from Kluyveromyces exhibited high hydrolytic activity but quite low transgalactosylation activity. Also the affinity for the donors (lactose or lactulose) and the acceptors (lactose, lactulose or fructose) of transgalactosylated galactose was dependent on the enzyme origin, as reflected by the Michaelis constants obtained in the synthesis of galacto-oligosaccharides, fructosyl-galacto-oligosaccharides and lactulose. Finally, the balance between transgalactosylation and hydrolytic activities of β-galactosidases could be tuned by changing the concentration of galactose donor. Copyright © 2014 Elsevier Inc. All rights reserved.

Can Lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy.

PubMed

Ziada, Dina H; Soliman, Hanan H; El Yamany, Saher A; Hamisa, Manal F; Hasan, Azza M

2013-09-01

Minimal hepatic encephalopathy (MHE) is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probiotics as alternative therapy in MHE. This is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic (Lactobacillus acidophilus) and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy (MRS) examination to study brain metabolites, mainly choline (Cho), myo-inositol (mI), glutamine+glutamate (Glx) and creatinin (Cre). Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4weeks. The probiotic was better tolerated than lactulose. The relative risk reduction (RRR) of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat (NNT) of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The mI/Cre and (Cho+mI)/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group. Both probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All

Functional cream cheese supplemented with Bifidobacterium animalis subsp. lactis DSM 10140 and Lactobacillus reuteri DSM 20016 and prebiotics.

PubMed

Speranza, Barbara; Campaniello, Daniela; Monacis, Noemi; Bevilacqua, Antonio; Sinigaglia, Milena; Corbo, Maria Rosaria

2018-06-01

The aim of this study was to develop a functional fresh cream cheese with Bifidobacterium animalis subsp. lactis DSM 10140 or Lactobacillus reuteri DSM 20016 and prebiotics (inulin, FOS and lactulose). The research was divided into two steps: in vitro evaluation of the effects of prebiotic compounds; validation at laboratory level with production of functional cream mini-cheeses. Prebiotics showed a protective effect: B. animalis subsp. lactis DSM 10140 cultivability on Petri dishes was positively influenced by lactulose, whereas fructooligosaccharides (FOS) were the prebiotic compounds able to prolong Lb. reuteri DSM 20016 cultivability. At 30 °C, a prolongation of the death time (more than 300 days) was observed, while the controls showed death time values about 100 days. At 45 °C, death time values increased from 32.2 (control) to 33, 35, and 38 days in the samples added with FOS, inulin and lactulose, respectively. Lactulose and FOS were chosen to be added to cream mini-cheeses inoculated with B. animalis subsp. lactis DSM 10140 and Lb. reuteri DSM 20016, respectively; the proposed functional cream cheese resulted in a product with favourable conditions for the viability of both probiotics which maintained cultivable cells above the recommended level during 28 days of storage at 4 °C with good sensory characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rifaximin: a review of its use in reducing recurrence of overt hepatic encephalopathy episodes.

PubMed

Scott, Lesley J

2014-12-01

Oral rifaximin 550 mg (Refero(®); Targaxan(®); Tixteller(®); Xifaxan(®)) twice daily, either alone or more commonly with medicines containing lactulose, is approved in several countries, including the UK, EU and USA, for use in adults with liver disease to reduce the recurrence of episodes of overt hepatic encephalopathy (HE). Rifaximin is a broad-spectrum antibacterial that acts locally in the gut to reduce intestinal flora, including ammonia-producing species, with hyperammonaemia considered to play a central role in the pathogenesis of HE. In a 6-month, multinational trial in patients with liver disease, rifaximin 550 mg twice daily (± lactulose) was an effective and well tolerated treatment for reducing the recurrence of HE episodes. At study end, rifaximin therapy significantly prolonged the time to the first breakthrough HE episode compared with placebo (± lactulose), irrespective of geographical region or baseline patient and disease characteristics. Rifaximin treatment also significantly reduced HE-related hospitalizations and improved health-related quality of life compared with placebo. Furthermore, the efficacy of rifaximin with or without lactulose in reducing the recurrence of overt HE episodes was maintained after up to 2.5 years of treatment, with no new safety signals arising during this period. This article reviews the pharmacology and therapeutic efficacy of rifaximin 550 mg twice daily in reducing the recurrence of overt HE episodes in adults with liver disease.

Assessment of in Vitro Digestibility of Dietary Carbohydrates Using Rat Small Intestinal Extract.

PubMed

Ferreira-Lazarte, Alvaro; Olano, Agustín; Villamiel, Mar; Moreno, F Javier

2017-09-13

There are few studies on the assessment of digestibility of nondigestible carbohydrates, despite their increasingly important role in human health. In vitro digestibility of a range of dietary carbohydrates classified as digestible (maltose, sucrose, and lactose), well-recognized (lactulose, fructooligosaccharides (FOS), and two types of galactooligosaccharides (GOS) differing in the predominant glycosidic linkage), and potential (lactosucrose and GOS from lactulose, OsLu) prebiotics using a rat small intestinal extract (RSIE) under physiological conditions of temperature and pH is described. Recognized and potential prebiotics were highly resistant to RSIE digestion although partial hydrolysis at different extents was observed. FOS and lactulose were the most resistant to digestion, followed closely by OsLu and more distantly by both types of GOS and lactosucrose. In GOS, β(1 → 6) linkages were more resistant to digestion than β(1 → 4) bonds. The reported in vitro digestion model is a useful, simple, and cost-effective tool to evaluate the digestibility of dietary oligosaccharides.

PillCam(TradeMark), a Noninvasive Endoscopic Device for the Measurement of Gastrointestinal Motility Changes

NASA Technical Reports Server (NTRS)

Vaksman, Zahman; Crady, Camille; Raju, G. S.; Putcha, Lakshmi

2007-01-01

Introduction: Bioavailability and effectiveness of drugs given by mouth are governed in part by gastrointestinal (GI) motility and function. Microgravity has been shown to decrease GI motility as indicated by a 3 fold increase in gastrointestinal transit time (GITT). The PillCam(TradeMark), an endoscopic camera embedded in a capsule, is a novel noninvasive and unobtrusive device that is used for the diagnosis of GI pathology. The purpose of this study is to evaluate the usefulness of PillCam(TradeMark) as an alternative to the Lactulose Breath Hydrogen Test (LBHT) for estimating GI motility. The sensitivity and applicability of this device for detection and estimation of the effect of promethazine, a deterrent, and caffeine, a prokinetic, on GI motility were also examined. Method: In this semi-randomized cross-over design study, six male and six female subjects were administered the following 4 treatments: PillCam(TradeMark) alone, PillCam(TradeMark)+Lactulose (10g), PillCam(TradeMark)+caffeine (200mg), and PillCam(TradeMark)+Promethazine (50mg). Results: GITT ranged between 1:24 and 7:52 hr:min. Lactulose did not alter GITT. A significant increase in GITT was noticed after administration of PMZ when compared to values from PillCam(TradeMark) treatment alone or PillCam(TradeMark)+Lactulose treatment. No difference in GITT after caffeine treatment was noticed. While there were no gender related differences in GITT after administration of PillCam(TradeMark) or with lactulose, a significant difference (p<.05) between genders was observed after promethazine administration with mean GITT higher in males (5:50 hr:min) than females (4:15 hr:min). Conclusion: The PillCam(TradeMark) capsule is applicable for the determination of GITT using time stamped GI images. It can be successfully used for the assessment of drug induced changes in GI motility and therefore, may be applicable for microgravity and analog environment studies on GI motility and function.

RiMINI - the influence of rifaximin on minimal hepatic encephalopathy (MHE) and on the intestinal microbiome in patients with liver cirrhosis: study protocol for a randomized controlled trial.

PubMed

Schulz, Christian; Schütte, Kerstin; Kropf, Siegfried; Schmitt, Friedhelm C; Vasapolli, Riccardo; Kliegis, Leon M; Riegger, Antonia; Malfertheiner, Peter

2016-02-29

Hepatic encephalopathy (HE) is a clinically significant complication of liver cirrhosis impacting on the patients' quality of life. Minimal hepatic encephalopathy (MHE) is diagnosed by psychometric tests, found in up to 80 % of patients with liver cirrhosis and carries a high risk of progression to overt HE. Continuous therapy with rifaximin in combination with lactulose significantly reduces the risk of overt HE, recurrence of HE and HE-related hospitalizations in randomized, double-blind, placebo-controlled clinical trials. Rifaximin is approved for the therapy of overt HE in Germany. Treatment with lactulose has been shown to improve cognitive functions in patients with liver cirrhosis. Data from prospective clinical trials comparing the efficacy of rifaximin alone against a combination of rifaximin and lactulose in the treatment of MHE are scarce. Changes in the microbiome of the upper and lower gastrointestinal tract as a result of therapy with rifaximin have not yet been addressed in clinical studies. RiMINI is a monocentric exploratory pilot study on 60 patients with MHE as assessed by critical flicker frequency (CFF). Additionally, visual evoked potentials' (VEP) testing, electroencephalography (EEG) and psychometric testing (NCT-A) will be carried out. Patients will be randomized to treatment either with rifaximin alone (550 mg twice daily (bid) continuously for a period of 3 months) or with rifaximin (550 mg bid continuously) in combination with lactulose (30-60 ml daily) for 3 months. An esophagogastroduodenoscopy (EGD) will be performed at baseline, at the end of treatment and 6 and 12 weeks after the end of treatment to obtain gastric and duodenal biopsies and aspirates. The samples will be analyzed for their content of specific bacterial taxae by applying next generation sequencing (NGS) after rRNA isolation to identify the microbiome of the stomach and duodenum, and of the gut, in patients with liver cirrhosis and MHE before and after therapy

Evaluation of Hepatoprotective Effect of Curcumin on Liver Cirrhosis Using a Combination of Biochemical Analysis and Magnetic Resonance-Based Electrical Conductivity Imaging

PubMed Central

Kyung, Eun Jung; Kim, Hyun Bum; Hwang, Eun Sang; Lee, Seok; Choi, Bup Kyung; Lim, Sang Moo; Kwon, Oh In

2018-01-01

In oriental medicine, curcumin is used to treat inflammatory diseases, and its anti-inflammatory effect has been reported in recent research. In this feasibility study, the hepatoprotective effect of curcumin was investigated using a rat liver cirrhosis model, which was induced with dimethylnitrosamine (DMN). Together with biochemical analysis, we used a magnetic resonance-based electrical conductivity imaging method to evaluate tissue conditions associated with a protective effect. The effects of curcumin treatment and lactulose treatment on liver cirrhosis were compared. Electrical conductivity images indicated that liver tissues damaged by DMN showed decreased conductivity compared with normal liver tissues. In contrast, cirrhotic liver tissues treated with curcumin or lactulose showed increased conductivity than tissues in the DMN-only group. Specifically, conductivity of cirrhotic liver after curcumin treatment was similar to that of normal liver tissues. Histological staining and immunohistochemical examination showed significant levels of attenuated fibrosis and decreased inflammatory response after both curcumin and lactulose treatments compared with damaged liver tissues by DMN. The conductivity imaging and biochemical examination results indicate that curcumin's anti-inflammatory effect can prevent the progression of irreversible liver dysfunction. PMID:29887757

Noninvasive Ph-telemetric Measurement of Gastrointestinal Function

NASA Technical Reports Server (NTRS)

Tietze, Karen J.

1991-01-01

The purpose of this study was to gain experience with and validate the Heidelberg pH-telemetric methodology in order to determine if the pH-telemetric methodology would be a useful noninvasive measure of gastrointestinal transit time for future ground-based and in-flight drug evaluation studies. The Heidelberg pH metering system is a noninvasive, nonradioactive telemetric system that, following oral ingestion, continuously measures intraluminal pH of the stomach, duodenum, small bowel, ileocecal junction, and large bowel. Gastrointestinal motility profiles were obtained in normal volunteers using the lactulose breath-hydrogen and Heidelberg pH metering techniques. All profiles were obtained in the morning after an overnight fast. Heidelberg pH profiles were obtained in the fasting and fed states; lactulose breath-hydrogen profiles were obtained after a standard breakfast. Mouth-to-cecum transit time was measured as the interval from administration of lactulose (30 ml; 20 g) to a sustained increase in breath-hydrogen of 10 ppm or more. Gastric emptying time was measured as the interval from the administration of the Heidelberg capsule to a sustained increase in pH of three units or more.

A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients

PubMed Central

Sigalet, David L; Kravarusic, Dragan; Butzner, Decker; Hartmann, Bolette; Holst, Jens J; Meddings, Jon

2013-01-01

BACKGROUND/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release. METHODS: With ethics board approval, pediatric patients hospitalized with CD were studied; controls were recruited from local schools. Inclusion criteria were endoscopy-confirmed CD (primarily of the small intestine) with a disease activity index >150. Fasting and post-prandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose/mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean [± SD] age 15.3±1.3 years) and 10 controls (10.3±1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose/mannitol recovery; all normalized with disease remission. The change in the lactulose/mannitol ratio was due to both reduced lactulose and increased mannitol absorption. CONCLUSIONS: These findings suggest that pediatric patients with acute ileal CD have decreased postprandial GLP-2 release, reduced glucose absorption and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies as a therapy in CD patients; further studies of the effects of inflammation and the GLP-2 axis are recommended. PMID:24106731

Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.

PubMed

Kang, S H; Lee, Y B; Lee, J-H; Nam, J Y; Chang, Y; Cho, H; Yoo, J-J; Cho, Y Y; Cho, E J; Yu, S J; Kim, M Y; Kim, Y J; Baik, S K; Yoon, J-H

2017-11-01

Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth. To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications. We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding. In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338). In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy. © 2017 John Wiley & Sons Ltd.

Management of Hepatic Encephalopathy in the Hospital

PubMed Central

Leise, Michael D.; Poterucha, John J.; Kamath, Patrick S.; Kim, W. Ray

2014-01-01

Hepatic encephalopathy (HE) develops in about 50% of patients with cirrhosis and is one of the features of decompensated cirrhosis. The inpatient incidence of HE is approximately 23,000/year and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails two phases, induction and maintenance of remission. Most cases of significant hepatic encephalopathy are precipitated by infection, gastrointestinal bleeding, medications or other culprits. All patients should be evaluated for secondary triggers of HE and treatment should be initiated with a non-absorbable disaccharide (i.e. lactulose) in most cases. Rifaximin (off-label) can be added in patients not responding to lactulose. Neomycin is a less preferable alternative to rifaximin, due to its side effect profile. Other therapies including zinc, LOLA, and branch chain amino acids can be considered for patients not responding to a disaccharide and non-absorbable antibiotic. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe hepatic encephalopathy who do not respond to medical therapy. It is critically important that patients hospitalized with significant hepatic encephalopathy continue a maintenance medication(s) at the time of dismissal to prevent further episodes. Patients with a 1st time episode of HE can be placed on lactulose and careful instruction should be provided to patient and caregiver about titration of dose to achieve 3 bowel movements per day. Patients with recurrent HE episodes despite lactulose benefit from the addition of rifaximin which decreases the frequency of recurrent HE episodes and related hospitalizations. Lastly, patients and their families should be counselled about the risk of motor vehicle accidents which

A Randomized, Double-Blind, Placebo-Controlled Trial of Rifaximin, a Nonabsorbable Antibiotic, in the Treatment of Tropical Enteropathy

PubMed Central

Trehan, Indi; Shulman, Robert J.; Ou, Ching-Nan; Maleta, Kenneth; Manary, Mark J.

2009-01-01

OBJECTIVES Tropical enteropathy is characterized by an increased urinary lactulose-to-mannitol (L:M) ratio on a site-specific sugar absorption test and is associated with increased intestinal permeability and decreased nutrient absorptive capacity. The etiology of tropical enteropathy is postulated to be intestinal bacterial overgrowth. This study tested the hypothesis that treatment with a nonabsorbable, broad-spectrum antibiotic, rifaximin, reduces the L:M ratio in rural Malawian children, among whom tropical enteropathy is common. METHODS All children aged 3–5 years from one village were enrolled in a randomized, double-blind, placebo-controlled trial of treatment with rifaximin for 7 days. The L:M ratio was measured before and after treatment, and the change in the L:M ratio was the primary outcome. Secondary outcomes were changes in the urinary sucrose-to-lactulose (SUC:L) and sucralose-to-lactulose (SCL:L) ratios, as well as changes in the fractions of each test sugar recovered in the urine. RESULTS A total of 144 children participated in this study, of whom 76% had an elevated L:M ratio on enrollment (L:M≥0.10). Children who received rifaximin did not show an improvement in their L:M ratio compared with those who received placebo (−0.01±0.12 vs. 0.02±0.16, respectively, P = 0.51, mean±s.d.), nor were there significant differences between the two groups in excretion of lactulose, mannitol, sucralose, or sucrose, or in the SUC:L and SCL:L ratios. CONCLUSIONS Rifaximin had no effect on the tropical enteropathy of 3–5-year-old Malawian children, suggesting that small-bowel bacterial overgrowth is not an important etiological factor in this condition. PMID:19491826

Laxative overdose

MedlinePlus

Below are specific laxative drugs, with some brand names: Bisacodyl (Dulcolax) Cascara sagrada Castor oil Docusate (Colace) Docusate and phenolphthalein (Correctol) Glycerin suppositories Lactulose (Duphalac) Magnesium ...

Additional Common Bean in the Diet of Malawian Children Does Not Affect Linear Growth, but Reduces Intestinal Permeability.

PubMed

Agapova, Sophia E; Stephenson, Kevin B; Divala, Oscar; Kaimila, Yankho; Maleta, Kenneth M; Thakwalakwa, Chrissie; Ordiz, M Isabel; Trehan, Indi; Manary, Mark J

2018-02-01

Chronic malnutrition, as manifested by linear growth faltering, is pervasive among rural African children. Improvements in complementary feeding may decrease the burden of environmental enteric dysfunction (EED) and thus improve growth in children during the critical first 1000 d of development. We tested the hypothesis that systematically including common bean or cowpea into complementary feeding would reduce EED and growth faltering among children in rural Malawi. This was a double-blind clinical trial in which children 12-23 mo of age were randomly assigned to receive complementary feeding with 1 of 3 foods: roasted cowpea or common bean flour, or an isoenergetic amount of corn-soy blend as a control food for 48 wk. Children aged 12-23 mo received 155 kcal/d and thereafter until 35 mo received 200 kcal/d. The primary outcomes were change in length-for-age z score (LAZ) and improvements in a biomarker of EED, the percentage of lactulose (%L) excreted as part of the lactulose:mannitol dual-sugar absorption test. Anthropometric measurements and urinary %L excretion were compared between the 2 intervention groups and the control group separately with the use of linear mixed model analyses for repeated measures. A total of 331 children completed the clinical trial. Compliance with the study interventions was excellent, with >90% of the intervention flour consumed as intended. No significant effects on LAZ, change in LAZ, or weight-for-length z score were observed due to either intervention legume, compared to the control. %L was reduced with common bean consumption (effect estimate was -0.07 percentage points of lactulose, P = 0.0007). The lactulose:mannitol test was not affected by the legume intervention. The addition of common bean to complementary feeding of rural Malawian children during the second year of life led to an improvement in a biomarker of gut health, although this did not directly translate into improved linear growth. This trial was registered at

Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials.

PubMed

Saab, Sammy; Suraweera, Duminda; Au, Jennifer; Saab, Elena G; Alper, Tori S; Tong, Myron J

2016-07-01

Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization. The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose. The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I(2) statistic. Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47-2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42-1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25-6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33-0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26-0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52-1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52-1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73-2.10, P = 0.42). Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abdominal bloating

MedlinePlus

... Some other medicines or foods containing lactulose or sorbitol, may cause bloating. More serious disorders that may ... from foods with high levels of fructose or sorbitol. Avoid foods that can produce gas, such as ...

Medial and Lateral Plantar Nerve Entrapment

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... Metformin Warfarin Tramadol Lactulose Ranitidine News & Commentary Recent News After Concussion, Are Legs at Risk, Too? AHA: ... Fingers may become bluish. Am I Correct? Latest News News HealthDay Steroid Injections for Arthritic Hips: More ...

Gastrointestinal helminthiasis presenting with acute diarrhoea and constipation: report of two cases with a second pathology.

PubMed

Sobani, Z A; Shakoor, S; Malik, F N; Malik, E Z; Beg, M A

2010-08-01

Gastrointestinal helminthiasis in developing countries contributes to malnutrition and anemia. Diagnosis and treatment of helminthiasis, especially with low worm load is an unmet public health need in such settings. The infection may sometimes become manifest when a second pathology leads to purgation of the gastrointestinal tract. Two cases of helminthiasis are presented in which the infections only became amenable to diagnosis due to acute diarrhoea caused by giardiasis and lactulose administration. In the first case, acute giardiasis revealed Ascaris lumbricoides infestation, and in the second case primary helminthiasis (strongyloidiasis) was revealed by lactulose, and also led to Vibrio cholera bacteremia. These cases highlight the need to diagnose helminth infestations especially with low worm burdens by means of public health surveillance programmes. These cases highlight the need to diagnose helminth infestations especially with low worm burdens by means of public health surveillance programmes.

Osmotic and stimulant laxatives for the management of childhood constipation.

PubMed

Gordon, Morris; MacDonald, John K; Parker, Claire E; Akobeng, Anthony K; Thomas, Adrian G

2016-08-17

studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent (27/154) of PEG patients required additional therapies compared to 31% (47/150) of lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of magnesia over lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring

Multiple micronutrient supplementation transiently ameliorates environmental enteropathy in Malawian children aged 12-35 months in a randomized controlled clinical trial

USDA-ARS?s Scientific Manuscript database

Environmental enteropathy (EE) is subclinical, diffuse villous atrophy characterized by T cell infiltration of the small intestinal mucosa associated with nutrient malabsorption and stunting. EE is assessed by the lactulose:mannitol (L:M) test, whereby nonmetabolized sugars are ingested and quantifi...

Thermostability enhancement of cellobiose 2-epimerase from Caldicellulosiruptor saccharolyticus by site-directed mutagenesis

USDA-ARS?s Scientific Manuscript database

Cellobiose 2-epimerase from the thermophile Caldicellulosiruptor saccharolyticus (CsCE) catalyzes the isomerization of lactose into lactulose, a non-digestible disaccharide widely used in food and pharmaceutical industries. Semi-rational approaches were applied to enhance the thermostability of CsCE...

Management of hepatic encephalopathy in the hospital.

PubMed

Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray

2014-02-01

Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes

Overview of Optic Nerve Disorders

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Canaliculitis

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Levator Syndrome

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Peridontitis

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Overview of Tooth Disorders

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Cancers Affecting the Retina

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Overview of the Cranial Nerves

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Endophthalmitis

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Heavy Chain Diseases

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Overview of Functional Peripheral Arterial Disease

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Eyelid Growths

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Necrotizing Skin Infections

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Portal Hypertension

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Avoidant/Restrictive Food Intake Disorder

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Bullous Keratopathy

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Anal and Rectal Disorders

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About Body Water

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Ear Tumors

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Bacterial Nasal Infections

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Eyes, Bulging (Proptosis)

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Tonsillar Cellulitis and Abscess

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Bacterial Skin Infections

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Inflammation of the Orbit

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Overview of Rehabilitation

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Laryngoceles

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Eosinophilic Disorders

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Intestinal Obstruction

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Peripheral Ulcerative Keratitis

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Multiple Endocrine Neoplasia Syndromes

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White Blood Cell Disorders

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Overview of the Esophagus

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Perichondritis

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Lymphatic Disorders

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Overview of the Spleen

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Postprandial Hypotension

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Acute Mesenteric Ischemia

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Inflammation of the Penis

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Conjugate Gaze Palsies

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Trichiasis

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Dacryocystitis

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A randomized, double-blind, placebo-controlled trial of Rifaximin, a nonabsorbable antibiotic, in the treatment of tropical enteropathy

USDA-ARS?s Scientific Manuscript database

Tropical enteropathy is characterized by an increased urinary lactulose-to-mannitol (L:M) ratio on a site-specific sugar absorption test and is associated with increased intestinal permeability and decreased nutrient absorptive capacity. The etiology of tropical enteropathy is postulated to be intes...

Perturbed zinc homeostasis in rural 3-5-y-old Malawian children is associated with abnormalities in intestinal permeability attributed to tropical enteropathy

USDA-ARS?s Scientific Manuscript database

Tropical enteropathy and zinc deficiency are major public health problems worldwide. Tropical enteropathy is characterized by reduced mannitol absorption with normal or increased lactulose absorption when a dual sugar absorption test is administered, the results of which are reported as the lactulos...

Noncirrhotic Extrahepatic Portosystemic Shunt Causing Adult-Onset Encephalopathy Treated with Endovascular Closure

PubMed Central

Elnekave, Eldad; Belenky, Eugenia; Van der Veer, Lindsley

2015-01-01

A 54-year-old woman presented with a six-month history of episodic confusion and progressive ataxia. A comprehensive metabolic panel was notable for elevated values of alkaline phosphatase (161 U/L), total bilirubin (1.5 mg/dL), and serum ammonia of 300 umol/L (normal range 9–47). Hepatitis panel, relevant serological tests, tumor markers (CA-19-9, CEA), and urea cycle enzyme studies were unrevealing. Lactulose and rifaximin therapy failed to normalize serum ammonia levels. Imaging revealed a structural vascular abnormality communicating between an enlarged inferior mesenteric vein and the left renal vein, measuring 16 mm in greatest diameter. The diagnosis of congenital extrahepatic portosystemic shunt was made and endovascular shunt closure was performed using a 22 mm Amplatzer II vascular plug. Within a day, serum ammonia levels normalized. Lactulose and rifaximin were discontinued, and confusion and ataxia resolved. PMID:26199783

Mutagenicity of heated sugar-casein systems: effect of the Maillard reaction.

PubMed

Brands, C M; Alink, G M; van Boekel, M A; Jongen, W M

2000-06-01

The formation of mutagens after the heating of sugar-casein model systems at 120 degrees C was examined by the Ames test, using Salmonella typhimurium strain TA100. Several sugars (glucose, fructose, galactose, tagatose, lactose, and lactulose) were compared in their mutagenicities. Mutagenicity could be fully ascribed to Maillard reaction products and strongly varied with the kind of sugar. The differences in mutagenicity among the sugar-casein systems were caused by a difference in reaction rate and a difference in reaction mechanism. Sugars with a comparable reaction mechanism (glucose and galactose) showed a higher mutagenic activity corresponding with a higher Maillard reactivity. Disaccharides showed no mutagenic activity (lactose) or a lower mutagenic activity (lactulose) than their corresponding monosaccharides. Ketose sugars (fructose and tagatose) showed a remarkably higher mutagenicity compared with their aldose isomers (glucose and galactose), which was due to a difference in reaction mechanism.

Application of fluorescent tracer agent technology to point-of-care gastrointestinal permeability measurement

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Shieh, Jeng-Jong; Rogers, Thomas E.; Hall-Moore, Carla; Shaikh, Nurmohammad; Talcott, Michael; Tarr, Phillip I.

2016-03-01

Gut dysfunction, often accompanied by increased mucosal permeability to gut contents, frequently accompanies a variety of human intestinal inflammatory conditions. These disorders include inflammatory bowel diseases (e.g., Crohn's Disease) and environmental enteropathy and enteric dysfunction, a condition strongly associated with childhood malnutrition and stunting in resource poor areas of the world. The most widely used diagnostic assay for gastrointestinal permeability is the lactulose to mannitol ratio (L:M) measurement. These sugars are administered orally, differentially absorbed by the gut, and then cleared from the body by glomerular filtration in the kidney. The amount of each sugar excreted in the urine is measured. The larger sugar, lactulose, is minimally absorbed through a healthy gut. The smaller sugar, mannitol, in contrast, is readily absorbed through both a healthy and injured gut. Thus a higher ratio of lactulose to mannitol reflects increased intestinal permeability. However, several issues prevent widespread use of the L:M ratio in clinical practice. Urine needs to be collected over time intervals of several hours, the specimen then needs to be transported to an analytical laboratory, and sophisticated equipment is required to measure the concentration of each sugar in the urine. In this presentation we show that fluorescent tracer agents with molecular weights similar to those of the sugars, selected from our portfolio of biocompatible renally cleared fluorophores, mimic the L:M ratio test for gut permeability. This fluorescent tracer agent detection technology can be used to overcome the limitations of the L:M assay, and is amenable to point-of-care clinical use.

Environmental enteric dysfunction is associated with poor linear growth and can be identified by host fecal mRNAs

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) can be assessed by the lactulose:mannitol (L:M) test. Our objective was to determine if selected host fecal transcripts were correlated with EED, and whether transcripts and clinical characteristics could be used to predict EED in rural African children. Demog...

Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus

PubMed Central

Rezaie, Ali; Buresi, Michelle; Lembo, Anthony; Lin, Henry; McCallum, Richard; Rao, Satish; Schmulson, Max; Valdovinos, Miguel; Zakko, Salam; Pimentel, Mark

2017-01-01

Objectives: Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Methods: Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Results: Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. Conclusions: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research. PMID:28323273

Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus.

PubMed

Rezaie, Ali; Buresi, Michelle; Lembo, Anthony; Lin, Henry; McCallum, Richard; Rao, Satish; Schmulson, Max; Valdovinos, Miguel; Zakko, Salam; Pimentel, Mark

2017-05-01

Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.

Outcome of breath tests in adult patients with suspected small intestinal bacterial overgrowth

PubMed Central

Mattsson, Johanna; Minaya, Maria Teresa; Monegro, Milka; Lebwohl, Benjamin; Lewis, Suzanne K.; Green, Peter HR; Stenberg, Reidun

2017-01-01

Aim: The aim was to investigate breath test outcomes in patients with suspected SIBO and indicative symptoms of SIBO, diagnosed by breath testing. Background: Breath testing is used to detect small intestinal bacterial overgrowth (SIBO) by measuring hydrogen and methane produced by intestinal bacteria. Methods: This retrospective cross sectional study included 311 patients with gastrointestinal symptoms who underwent the breath test for evaluation of SIBO at Celiac Disease Center at Columbia University, New York, in 2014-2015. The patients were divided into two groups based on the physician’s choice: lactulose breath test group (72%) and glucose breath test group (28%). Among them, 38% had a history of celiac disease or non-celiac gluten sensitivity. Results: In total, 46% had a positive breath test: 18% were positive for methane, 24 % positive for hydrogen and 4% positive for both gases (p=0.014). Also, 50% had a positive lactulose breath result and 37% had a positive glucose breath result (p=0.036). The most common symptom for performing the breath test was bloating and the only clinical symptom that significantly showed a positive glucose breath test was increased gas (p=0.028). Conclusion: Lactulose breath test was more often positive than glucose breath test. Positivity for hydrogen was more common than methane. Bloating was the most frequently perceived symptom of the patients undergoing the breath test but the only statistically significant clinical symptom for a positive glucose breath test was increased gas. Furthermore, the results showed that there was no significant association between positive breath test result and gender, age, non-celiac gluten sensitivity or celiac disease. PMID:29118931

Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France.

PubMed

Kabeshova, Anastasiia; Ben Hariz, Soumaia; Tsakeu, Elyonore; Benamouzig, Robert; Launois, Robert

2016-07-01

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-α is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost-effectiveness of rifaximin-α used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events. A Markov model was used to estimate rifaximin-α cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-α pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY). The results indicate that rifaximin-α is a cost-effective treatment option with an incremental cost per QALY gained of €19,187 and €18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis. For the societal willingness to pay threshold of €27,000 per QALY gained, rifaximin-α in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes.

Poor predictive value of breath hydrogen response for probiotic effects in IBS.

PubMed

Yao, Chu K; Barrett, Jacqueline S; Philpott, Hamish; Chung, Alvin R T; van Langenberg, Daniel; Garg, Mayur; Gibson, Peter R

2015-12-01

Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics. In a randomized, double-blind, placebo-controlled trial, patients with IBS (Rome III) were randomized to either 65 mL/day fermented milk product containing probiotic (FMPP) or placebo for 6 weeks, followed by 6 weeks' open-label treatment and 6 weeks' withdrawal. Breath hydrogen responses to lactulose (15 g) and liquid-gastric emptying time were evaluated before and at the end of each treatment period. Symptoms were measured using a 100-mm visual analog scale. Loss of ERBHAL occurred in 36% of 23 patients receiving FMPP and 41% of 22 receiving placebo (P = 1.00). Amongst 40 patients who completed open-label FMPP treatment, ERBHAL was lost in a further 38%, continued in 25%, and regained in 10%. Similar variability occurred in the withdrawal phase. Variability was unrelated to changes in gastric emptying. No differences in symptom response were seen between treatment groups nor in relation to the loss or retention of ERBHAL. Breath hydrogen patterns after lactulose are poorly reproducible. No FMPP-specific effects on fermentation patterns or symptoms were observed. The presence of ERBHAL is not useful to predict symptomatic response to probiotic therapy in patients with IBS. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Intestinal Permeability and Glucagon-Like Peptide-2 in Children with Autism: A Controlled Pilot Study

ERIC Educational Resources Information Center

Robertson, Marli A.; Sigalet, David L.; Holst, Jens J.; Meddings, Jon B.; Wood, Julie; Sharkey, Keith A.

2008-01-01

We measured small intestinal permeability using a lactulose:mannitol sugar permeability test in a group of children with autism, with current or previous gastrointestinal complaints. Secondly, we examined whether children with autism had an abnormal glucagon-like peptide-2 (GLP-2) response to feeding. Results were compared with sibling controls…

Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation

PubMed Central

Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung; Lee, Ran

2016-01-01

Purpose To evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose. Methods Of 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis. Results The overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (<8 years), 0.53±0.12 g/kg/d (8 to <12 years), and 0.36±0.05 g/kg/d (12 to 15 years). The dose of lactulose was 1.99±0.43 mL/kg/d (<8 years) or 1.26±0.25 mL/kg/d (8 to <12 years). There was no significant correlation between CTT test value and initial dose of laxative, irrespective of the subgroup (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p=0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p=0.022). Conclusion CTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation. PMID:27738600

Replacement of digestible by resistant starch lowers diet-induced thermogenesis in healthy men.

PubMed

Heijnen, M L; Deurenberg, P; van Amelsvoort, J M; Beynen, A C

1995-03-01

The present study describes the effect of replacement of digestible starch by resistant starch (RS) on diet-induced thermogenesis (DIT), postprandial glucose and insulin responses, and colonic fermentation. Ten healthy males consumed three test meals, consisting of diluted, artificially-sweetened fruit syrup and either 50 g raw potato starch (550 g RS/kg), or 50 g pregelatinized potato starch (0 g RS/kg) or 30 g pregelatinized potato starch plus 20 g lactulose (670 g indigestible disaccharide/kg). The meals were served in the morning after an overnight fast. Each volunteer consumed each meal twice on six separate days in random order. Metabolic rate was measured by indirect calorimetry in the fasting state for 15 min and postprandially for 5 h. Shortly before and hourly up to 7 h after consumption of the test meal, end-expiratory breath samples were obtained for H2 and CH4 analysis. Shortly before the meal and 30, 60, 180, and 300 min postprandially, blood samples were taken for glucose and insulin analyses. Postprandial increases in glucose and insulin levels were proportional to the amount of digestible carbohydrate in the meal. Breath H2 and CH4 concentrations indicated that the pregelatinized starch was not fermented and that lactulose was fermented rapidly. Fermentation of the raw starch started only 6 to 7 h after consumption, resulting in a rise in breath H2 but not in CH4. The replacement of 27 g digestible starch by RS in a single meal lowered DIT by on average 90 kJ/5 h, as could also be calculated by assuming that RS does not contribute to DIT. The ingestion of lactulose resulted in a substantial rise in DIT which was most probably caused by its fermentation.

Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation.

PubMed

Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung; Lee, Ran; Bae, Sun Hwan

2016-09-01

To evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose. Of 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis. The overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (<8 years), 0.53±0.12 g/kg/d (8 to <12 years), and 0.36±0.05 g/kg/d (12 to 15 years). The dose of lactulose was 1.99±0.43 mL/kg/d (<8 years) or 1.26±0.25 mL/kg/d (8 to <12 years). There was no significant correlation between CTT test value and initial dose of laxative, irrespective of the subgroup (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p =0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p =0.022). CTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation.

Polyethylene glycol versus dual sugar assay for gastrointestinal permeability analysis: is it time to choose?

PubMed

van Wijck, Kim; Bessems, Babs Afm; van Eijk, Hans Mh; Buurman, Wim A; Dejong, Cornelis Hc; Lenaerts, Kaatje

2012-01-01

Increased intestinal permeability is an important measure of disease activity and prognosis. Currently, many permeability tests are available and no consensus has been reached as to which test is most suitable. The aim of this study was to compare urinary probe excretion and accuracy of a polyethylene glycol (PEG) assay and dual sugar assay in a double-blinded crossover study to evaluate probe excretion and the accuracy of both tests. Gastrointestinal permeability was measured in nine volunteers using PEG 400, PEG 1500, and PEG 3350 or lactulose-rhamnose. On 4 separate days, permeability was analyzed after oral intake of placebo or indomethacin, a drug known to increase intestinal permeability. Plasma intestinal fatty acid binding protein and calprotectin levels were determined to verify compromised intestinal integrity after indomethacin consumption. Urinary samples were collected at baseline, hourly up to 5 hours after probe intake, and between 5 and 24 hours. Urinary excretion of PEG and sugars was determined using high-pressure liquid chromatography-evaporative light scattering detection and liquid chromatography-mass spectrometry, respectively. Intake of indomethacin increased plasma intestinal fatty acid-binding protein and calprotectin levels, reflecting loss of intestinal integrity and inflammation. In this state of indomethacin-induced gastrointestinal compromise, urinary excretion of the three PEG probes and lactulose increased compared with placebo. Urinary PEG 400 excretion, the PEG 3350/PEG 400 ratio, and the lactulose/rhamnose ratio could accurately detect indomethacin-induced increases in gastrointestinal permeability, especially within 2 hours of probe intake. Hourly urinary excretion and diagnostic accuracy of PEG and sugar probes show high concordance for detection of indomethacin-induced increases in gastrointestinal permeability. This comparative study improves our knowledge of permeability analysis in man by providing a clear overview of both

Polyethylene glycol versus dual sugar assay for gastrointestinal permeability analysis: is it time to choose?

PubMed Central

van Wijck, Kim; Bessems, Babs AFM; van Eijk, Hans MH; Buurman, Wim A; Dejong, Cornelis HC; Lenaerts, Kaatje

2012-01-01

Background Increased intestinal permeability is an important measure of disease activity and prognosis. Currently, many permeability tests are available and no consensus has been reached as to which test is most suitable. The aim of this study was to compare urinary probe excretion and accuracy of a polyethylene glycol (PEG) assay and dual sugar assay in a double-blinded crossover study to evaluate probe excretion and the accuracy of both tests. Methods Gastrointestinal permeability was measured in nine volunteers using PEG 400, PEG 1500, and PEG 3350 or lactulose-rhamnose. On 4 separate days, permeability was analyzed after oral intake of placebo or indomethacin, a drug known to increase intestinal permeability. Plasma intestinal fatty acid binding protein and calprotectin levels were determined to verify compromised intestinal integrity after indomethacin consumption. Urinary samples were collected at baseline, hourly up to 5 hours after probe intake, and between 5 and 24 hours. Urinary excretion of PEG and sugars was determined using high-pressure liquid chromatography-evaporative light scattering detection and liquid chromatography-mass spectrometry, respectively. Results Intake of indomethacin increased plasma intestinal fatty acid-binding protein and calprotectin levels, reflecting loss of intestinal integrity and inflammation. In this state of indomethacin-induced gastrointestinal compromise, urinary excretion of the three PEG probes and lactulose increased compared with placebo. Urinary PEG 400 excretion, the PEG 3350/PEG 400 ratio, and the lactulose/rhamnose ratio could accurately detect indomethacin-induced increases in gastrointestinal permeability, especially within 2 hours of probe intake. Conclusion Hourly urinary excretion and diagnostic accuracy of PEG and sugar probes show high concordance for detection of indomethacin-induced increases in gastrointestinal permeability. This comparative study improves our knowledge of permeability analysis in man

Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children.

PubMed

Lima, Aldo A M; Anstead, Gregory M; Zhang, Qiong; Figueiredo, Ítalo L; Soares, Alberto M; Mota, Rosa M S; Lima, Noélia L; Guerrant, Richard L; Oriá, Reinaldo B

2014-01-01

To determine the impact of supplemental zinc, vitamin A, and glutamine alone or in combination on growth, intestinal barrier function, stress and satiety-related hormones among Brazilian shantytown children with low median height-for-age z-scores. A randomized, double-blind, placebo-controlled trial was conducted in children aged two months to nine years from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for testing (a total of 120 children) were as follows: (1) glutamine alone, n = 38; (2) glutamine plus vitamin A plus zinc, n = 37; and a placebo (zinc plus vitamin A vehicle) plus glycine (isonitrogenous to glutamine) control treatment, n = 38. Leptin, adiponectin, insulin-like growth factor (IGF-1), and plasma levels of cortisol were measured with immune-enzymatic assays; urinary lactulose/mannitol and serum amino acids were measured with high-performance liquid chromatography. ClinicalTrials.gov: NCT00133406. Glutamine treatment significantly improved weight-for-height z-scores compared to the placebo-glycine control treatment. Either glutamine alone or all nutrients combined prevented disruption of the intestinal barrier function, as measured by the percentage of lactulose urinary excretion and the lactulose:mannitol absorption ratio. Plasma leptin was negatively correlated with plasma glutamine (p = 0.002) and arginine (p = 0.001) levels at baseline. After glutamine treatment, leptin was correlated with weight-for-age (WAZ) and weight-for-height z-scores (WHZ) (p≤0.002) at a 4-month follow-up. In addition, glutamine and all combined nutrients (glutamine, vitamin A, and zinc) improved the intestinal barrier function in these children. Taken together, these findings reveal the benefits of glutamine alone or in combination with other gut-trophic nutrients in growing children via interactions with leptin.

Effect of a simethicone-containing tablet on colonic gas elimination in breath.

PubMed

Lifschitz, C H; Irving, C S; Smith, E O

1985-05-01

The effect of a tablet containing the antiflatulent, simethicone, on intestinal hydrogen (H2) elimination in breath was studied. In three trials, normal subjects (age 12-52 years) received, on subsequent days, lactulose or lactulose with two tablets of either simethicone or placebo in randomized order. Breath samples were collected over 210 min and analyzed by gas chromatography for H2. The time course of H2 expiration above baseline levels was calculated and compared for the three tests. No significant differences in transit time were found. Cumulative H2 expiration was significantly lower after simethicone compared to placebo. H2 production from stool incubated with simethicone or placebo indicated that the drug had no effect in reducing the fermentative production of H2 in vitro. Interestingly, the vehicle present in the tablets could be fermented by intestinal bacteria. Simethicone reduced the amount of H2 eliminated in breath, but this effect was offset partially by H2 production from the fermentation of unabsorbable substances used in the formulation of the tablets.

Effect of Daikenchuto (TJ-100) on abdominal bloating in hepatectomized patients.

PubMed

Hanazaki, Kazuhiro; Ichikawa, Kengo; Munekage, Masaya; Kitagawa, Hiroyuki; Dabanaka, Ken; Namikawa, Tsutomu

2013-04-27

To evaluate the clinical usefulness of Daikenchuto (DKT) in hepatecomized patients. Twenty patients were enrolled with informed consent. Two patients were excluded because of cancelled operations. The remaining 18 patients were randomly chosen for treatment with DKT alone or combination therapy of DKT and lactulose (n = 9, each group). Data were prospectively collected. Primary end points were Visual Analogue Scale (VAS) score for abdominal bloating, total Gastrointestinal Symptoms Rating Scale (GSRS) score for abdominal symptoms, and GSRS score for abdominal bloating. The VAS score for abdominal bloating and total GSRS score for abdominal symptoms recovered to levels that were not significantly different to preoperative levels by 10 d postoperation. Combination therapy of DKT and lactulose was associated with a significantly poorer outcome in terms of VAS and GSRS scores for abdominal bloating, total GSRS score, and total daily calorie intake, when compared with DKT alone therapy. DKT is a potentially effective drug for postoperative management of hepatectomized patients, not only to ameliorate abdominal bloating, but also to promote nutritional support by increasing postoperative dietary intake.

Effect of Daikenchuto (TJ-100) on abdominal bloating in hepatectomized patients

PubMed Central

Hanazaki, Kazuhiro; Ichikawa, Kengo; Munekage, Masaya; Kitagawa, Hiroyuki; Dabanaka, Ken; Namikawa, Tsutomu

2013-01-01

AIM: To evaluate the clinical usefulness of Daikenchuto (DKT) in hepatecomized patients. METHODS: Twenty patients were enrolled with informed consent. Two patients were excluded because of cancelled operations. The remaining 18 patients were randomly chosen for treatment with DKT alone or combination therapy of DKT and lactulose (n = 9, each group). Data were prospectively collected. Primary end points were Visual Analogue Scale (VAS) score for abdominal bloating, total Gastrointestinal Symptoms Rating Scale (GSRS) score for abdominal symptoms, and GSRS score for abdominal bloating. RESULTS: The VAS score for abdominal bloating and total GSRS score for abdominal symptoms recovered to levels that were not significantly different to preoperative levels by 10 d postoperation. Combination therapy of DKT and lactulose was associated with a significantly poorer outcome in terms of VAS and GSRS scores for abdominal bloating, total GSRS score, and total daily calorie intake, when compared with DKT alone therapy. CONCLUSION: DKT is a potentially effective drug for postoperative management of hepatectomized patients, not only to ameliorate abdominal bloating, but also to promote nutritional support by increasing postoperative dietary intake. PMID:23671738

The effect of red and black pepper on orocecal transit time.

PubMed

Vazquez-Olivencia, W; Shah, P; Pitchumoni, C S

1992-04-01

The effects of spices on intestinal peristalsis have not been studied in humans. In this pilot study we evaluated the effects of red pepper and black pepper on small intestinal peristalsis measuring orocecal transit time (OCTT) utilizing a lactulose hydrogen breath test. Subjects included 16 healthy volunteers. The lactulose hydrogen breath test was done on different days with or without the powdered red pepper (2 g) or black pepper (1.5 g) given in gelatin capsules. The baseline orocecal transit time was increased significantly after red pepper consumption (88 +/- 37.2 to 128 +/- 63.2 min, p less than 0.01). Although the change in OCTT was not statistically significant, a similar trend was observed after black pepper consumption (90 +/- 51 min to 122 +/- 88 min., p = 0.09). The pathogenesis of increased OCTT after red pepper may be attributed to the known effects of capsaicin, a constituent noted to be a potent stimulator of many biologically active peptides. Although the effect of spices on OCTT is likely to vary depending upon the dose and nature of the product, it is of clinical importance in the management of various gastrointestinal tract disorders.

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil.

PubMed

Mitter, Sumeet S; Oriá, Reinaldo B; Kvalsund, Michelle P; Pamplona, Paula; Joventino, Emanuella Silva; Mota, Rosa M S; Gonçalves, Davi C; Patrick, Peter D; Guerrant, Richard L; Lima, Aldo A M

2012-01-01

Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice weekly), or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-for-height z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6) later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. Thirty-seven children were apolipoprotein E4(+), with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+) children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+) children and improved delta lactulose/mannitol. Apolipoprotein E4(-) children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. During development, apolipoprotein E4 may function concomitantly with gut-tropic nutrients to

Plasma endotoxin core antibody concentration and linear growth are unrelated in rural Malawian children aged 2-5 years.

PubMed

Benzoni, Nicole; Korpe, Poonum; Thakwalakwa, Chrissie; Maleta, Ken; Stephenson, Kevin; Manary, Micah; Manary, Mark

2015-06-24

Environmental enteropathy is subclinical inflammation of the upper gastrointestinal tract associated with reduced linear growth in developing countries. Usually investigators have used biopsy or a dual sugar absorption test to assess environmental enteropathy. Such tests are time and resource intensive, restricting their utility as screening methods. Serum endotoxin core antibody (EndoCab) concentration is a potential indicator of intestinal inflammation and integrity, and thus may be useful to predict environmental enteropathy. We analyzed the association of serum EndoCab levels versus linear growth and lactulose-mannitol assay results in 2-5 year old rural Malawian children. This was an observational study of 388 rural, asymptomatic Malawian children who had anthropometric measurements taken at least every 3 months since birth. In June and July 2011, dual sugar permeability tests were performed and serum samples were drawn for EndoCab assays. Pearson correlation, Student's t test and multivariable linear regression were used to compare ln EndoCab concentrations with height-for-age z scores (HAZ) at time of sampling and 3 months later. Identical analysis was also performed for ln EndoCab versus measurements from dual sugar permeability testing performed in conjunction with serum sampling. In a subgroup of children with anthropometric data in the months prior to serum sampling, Pearson correlation was used to estimate the relationship between ln EndoCab and recent linear growth. Ln EndoCab concentrations were not correlated with HAZ at time of measurement (B = -0.078, P = 0.14) nor change in HAZ over the subsequent 3 months HAZ (B = -0.018, P = 0.27). EndoCab concentration was not associated with %lactulose excretion (B < 0.001, P = 0.98) nor the lactulose:mannitol ratio (B = 0.021, P = 0.62). Subgroup analysis also did not reveal any significant association between EndoCab and recent growth. EndoCab titers were not correlated with measurements of growth or

Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison.

PubMed

Bianchi, G P; Marchesini, G; Fabbri, A; Rondelli, A; Bugianesi, E; Zoli, M; Pisi, E

1993-05-01

In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+0.2 (SD 1.4) g vs. -1.7 (2.4); P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.

13C Mannitol as a Novel Biomarker for Measurement of Intestinal Permeability

PubMed Central

Grover, Madhusudan; Camilleri, Michael; Hines, Jolaine; Burton, Duane; Ryks, Michael; Wadhwa, Akhilesh; Sundt, Wendy; Dyer, Roy; Singh, Ravinder J.

2016-01-01

Background Gastrointestinal (GI) and non-GI disorders are associated with altered intestinal permeability, which can be measured in vivo by urinary excretion after oral lactulose and mannitol ingestion. Inadvertent dietary consumption of 12Carbon (12C, regular) mannitol in food or from other sources may interfere with the test’s interpretation. 13Carbon (13C) constitutes 1% of carbon in nature and 13C mannitol is a stable isotope. Our aim was to determine performance of 13C mannitol for measurement of intestinal permeability. Methods Ten healthy volunteers underwent intestinal permeability assay using co-administered 12C mannitol, 13C mannitol and lactulose, followed by timed urine collections. Urinary sugar concentrations were measured using tandem high performance liquid chromatography-mass spectrometry. Key Results We found that 13C mannitol can be distinguishable from 12C mannitol on tandem mass spectrometry. Additionally, 13C mannitol had ~20-fold lower baseline contamination compared to 12C mannitol. We describe here the 13C mannitol assay method for measurement of intestinal permeability. Conclusions & Inferences In conclusion, 13C mannitol is superior to 12C mannitol for measurement of intestinal permeability. It avoids issues with baseline contamination and erratic excretions during the testing period. PMID:26914765

(13) C mannitol as a novel biomarker for measurement of intestinal permeability.

PubMed

Grover, M; Camilleri, M; Hines, J; Burton, D; Ryks, M; Wadhwa, A; Sundt, W; Dyer, R; Singh, R J

2016-07-01

Gastrointestinal (GI) and non-GI disorders are associated with altered intestinal permeability, which can be measured in vivo by urinary excretion after oral lactulose and mannitol ingestion. Inadvertent dietary consumption of (12) Carbon ((12) C, regular) mannitol in food or from other sources may interfere with the test's interpretation. (13) Carbon ((13) C) constitutes 1% of carbon in nature and (13) C mannitol is a stable isotope. Our aim was to determine the performance of (13) C mannitol for measurement of intestinal permeability. Ten healthy volunteers underwent intestinal permeability assay using coadministered (12) C mannitol, (13) C mannitol and lactulose, followed by timed urine collections. Urinary sugar concentrations were measured using tandem high performance liquid chromatography-mass spectrometry. We found that (13) C mannitol can be distinguishable from (12) C mannitol on tandem mass spectrometry. In addition, (13) C mannitol had ~20-fold lower baseline contamination compared to (12) C mannitol. We describe here the (13) C mannitol assay method for the measurement of intestinal permeability. In conclusion, (13) C mannitol is superior to (12) C mannitol for measurement of intestinal permeability. It avoids issues with baseline contamination and erratic excretions during the testing period. © 2016 John Wiley & Sons Ltd.

[Influence of proton pump inhibitors on intestinal fermentative profile: a case-control study].

PubMed

Senderovky, Melisa; Lasa, Juan; Dima, Guillermo; Peralta, Daniel; Argüello, Mariano; Soifer, Luis

2014-01-01

Proton pump inhibitors could have an impact on the results of breath tests performed in patients with irritable bowel syndrome. This impact could be due to the development of small intestine bacterial overgrowth. To compare the prevalence of fermentative profile alterations of irritable bowel syndrome patients exposed and not-exposed to proton pump inhibitor therapy. Subjects with irritable bowel syndrome were enrolled. A validated questionnaire assessing symptom severity as well as proton pump inhibitor treatment was delivered. A lactulose breath test was undertaken by each enrolled subject. Fermentative profile (area under the curve of hydrogen excretion/time) was compared between proton pump inhibitors consumers and non-consumers. Furthermore, small intestine bacterial overgrowth prevalence was compared. Two hundred and twenty five patients were enrolled. No significant differences were found on the fermentative profile between groups [AUC mediana 3,776 (rango 2,124-5,571) vs 4,347 (rango 2,038-5,481), P = 0.3]. Small intestine bacterial overgrowth prevalence was similar as well [33% vs 27.5%]. These differences remained non-significant after adjusting for proton pump inhibitor dose and treatment time. Surprisingly, symptom score was significantly higher in those patients under proton pump inhibitor therapy [28.5 (23-26) vs 23 (15-29), P = 0.01]. Proton pump inhibitors have no significant influence on lactulose breath tests, regardless of the dosage and time of administration.

Adaptation of exercise-induced stress in well-trained healthy young men.

PubMed

JanssenDuijghuijsen, Lonneke M; Keijer, Jaap; Mensink, Marco; Lenaerts, Kaatje; Ridder, Lars; Nierkens, Stefan; Kartaram, Shirley W; Verschuren, Martie C M; Pieters, Raymond H H; Bas, Richard; Witkamp, Renger F; Wichers, Harry J; van Norren, Klaske

2017-01-01

What is the central question of this study? Exercise is known to induce stress-related physiological responses, such as changes in intestinal barrier function. Our aim was to determine the test-retest repeatability of these responses in well-trained individuals. What is the main finding and its importance? Responses to strenuous exercise, as indicated by stress-related markers such as intestinal integrity markers and myokines, showed high test-retest variation. Even in well-trained young men an adapted response is seen after a single repetition after 1 week. This finding has implications for the design of studies aimed at evaluating physiological responses to exercise. Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com), we determined the test-retest repeatability in responses to exercise in well-trained individuals. Eleven well-trained men (27 ± 4 years old) completed an exercise protocol that consisted of intensive cycling intervals, followed by an overnight fast and an additional 90 min cycling phase at 50% of maximal workload the next morning. The day before (rest), and immediately after the exercise protocol (exercise) a lactulose and rhamnose solution was ingested. Markers of energy metabolism, lactulose-to-rhamnose ratio, several cytokines and potential stress-related markers were measured at rest and during exercise. In addition, untargeted urine metabolite profiles were obtained. The complete procedure (Test) was repeated 1 week later (Retest) to assess repeatability. Metabolic effect parameters with regard to energy metabolism and urine metabolomics were similar for both the Test and Retest period, underlining comparable exercise load. Following exercise, intestinal permeability (1 h plasma lactulose-to-rhamnose ratio) and the serum interleukin-6, interleukin-10, fibroblast growth factor-21 and muscle creatine

Effect of Daily Supine LBNP Exercise on Gastrointestinal Motility During Antiorthostatic Bedrest in Normal Subjects

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi; DeKerlegand, D.; Hargens, Alan R. (Technical Monitor)

1997-01-01

Space flight alters gastrointestinal (GI) function in general, and GI motility, in particular. This can decrease appetite, affect the body's ability to absorb nutrients, fluids and electrolytes, and contribute to a negative energy balance. Antiorthostatic bed rest (ABR) has been used to simulate microgravity-induced physiological changes in human subjects. The objective of this investigation is to determine if daily supine lower body negative pressure (LBNP) exercise will maintain GI motility at near normal levels during ABR. Eight subjects participated in the study protocol consisting of an ambulatory phase scheduled before bedrest periods and two 14 day bed rest (6 deg head-down tilt) periods, once with and another time without exercise. Supine treadmill running in an LBNP chamber was used for exercise. Mouth-to-cecum transit time (MCTT) of lactulose was measured indirectly using the rise in breath hydrogen level after oral administration of lactulose (20 g) following a standard low-fiber breakfast. GI motility during ambulatory and ABR periods was assessed using MCTT data. Results of this Study indicate that GI motility during ABR without exercise decreased by 45% [MCTT +/- S.E.M. 56.2 +/- 6.0 (Ambulatory); 87.3 +/- 8.3 (ABR)]. Supine LBNP exercise did not significantly alter this reduction in GI motility during ABR [MCTT +/- S.E.M. 81.3 +/- 4.2 (Exercise); 87.3 +/- 8.3 (No Exercise)]. These results suggest that supine LBNP exercise may not be an effective countermeasure for microgravity-induced decrements in GI motility and function.

The effect of Saccharomyces boulardii in patients eligible for liver transplantation.

PubMed

Liboredo, Juliana Costa; Ferrari, Maria de Lourdes Abreu; Vilela, Eduardo Garcia; Lima, Agnaldo Soares; Correia, Maria Isabel Toulson Davisson

2014-09-12

The aim of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability, laboratory parameters and MELD and Child-Pugh severity scores in cirrhotic patients eligible for liver transplantation. Eighteen patients followed in a Transplant Outpatient Clinic were evaluated immediately before the beginning of treatment, after a 30-day period of treatment period with probiotics and at the end of the second study month (after a thirty-day period without probiotics). Fifteen healthy controls also underwent the intestinal permeability test (lactulose/mannitol). Before the probiotic, the median lactulose/ mannitol ratio was greater in the cirrhotic patients (0.0209, range 0.0012-0.1984) compared to the healthy controls (0.0030, range 0.0020-0.0013) (p < 0.05). Eight of fifteen patients, half of whom had ascites, showed increased intestinal permeability above the higher value observed in the controls. No significant association was found between the severity scores for liver disease, age, presence of ascites and intestinal permeability immediately before the beginning of study. After treatment with S. boulardii, there was no improvement in intestinal permeability or significant differences in the laboratory parameters for the three evaluations. Patients eligible for liver transplants presented with increased intestinal permeability compared to healthy controls. A thirty-day treatment with S. boulardii did not improve this intestinal permeability or the severity scores, nor did it impact the laboratory parameters. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Balance of Autonomic Nervous System Predicts Who Benefits from a Self-management Intervention Program for Irritable Bowel Syndrome.

PubMed

Jarrett, Monica E; Cain, Kevin C; Barney, Pamela G; Burr, Robert L; Naliboff, Bruce D; Shulman, Robert; Zia, Jasmine; Heitkemper, Margaret M

2016-01-31

To determine if potential biomarkers can be used to identify subgroups of people with irritable bowel syndrome (IBS) who will benefit the most or the least from a comprehensive self-management (CSM) intervention. In a two-armed randomized controlled trial a CSM (n = 46) was compared to a usual care (n = 46) group with follow-up at 3 and 6 months post randomization. Biomarkers obtained at baseline included heart rate variability, salivary cortisol, interleukin-10 produced by unstimulated peripheral blood mononuclear cells, and lactulose/mannitol ratio. Linear mixed models were used to test whether these biomarkers predicted improvements in the primary outcomes including daily abdominal pain, Gastrointestinal Symptom score and IBS-specific quality of life. The nurse-delivered 8-session CSM intervention is more effective than usual care in reducing abdominal pain, reducing Gastrointestinal Symptom score, and enhancing quality of life. Participants with lower nighttime high frequency heart rate variability (vagal modulation) and increased low frequency/high frequency ratio (sympathovagal balance) had less benefit from CSM on abdominal pain. Salivary cortisol, IL-10, and lactulose/mannitol ratio were not statistically significant in predicting CSM benefit. Baseline symptom severity interacts with treatment, namely the benefit of CSM is greater in those with higher baseline symptoms. Cognitively-focused therapies may be less effective in reducing abdominal pain in IBS patients with higher sympathetic tone. Whether this a centrally-mediated patient characteristic or related to heightened arousal remains to be determined.

Sodium benzoate for treatment of hepatic encephalopathy.

PubMed

Misel, Michael L; Gish, Robert G; Patton, Heather; Mendler, Michel

2013-04-01

Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction.

Sodium Benzoate for Treatment of Hepatic Encephalopathy

PubMed Central

Misel, Michael L.; Patton, Heather; Mendler, Michel

2013-01-01

Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction. PMID:24711766

Rifaximin for small intestinal bacterial overgrowth in patients without irritable bowel syndrome.

PubMed

Boltin, Doron; Perets, Tsachi Tsadok; Shporn, Einav; Aizic, Shoshana; Levy, Sigal; Niv, Yaron; Dickman, Ram

2014-10-17

Rifaximin is a minimally absorbed antibiotic with high luminal activity, used to treat various gastrointestinal diseases. Although rifaximin has been proposed as first line treatment for small intestinal bacterial overgrowth (SIBO), few data are available regarding its efficacy in non-IBS subjects. We aimed to assess the ability of rifaximin to normalize lactulose-H2 breath tests in non-IBS subjects with symptoms suggestive of SIBO. Consecutive non-IBS patients presenting with bloating and flatulence were prospectively recruited and submitted to lactulose-H2 breath testing (LBT). Patients who had a positive result were offered rifaximin 1200 mg daily for 10 days. Breath testing was repeated two weeks after treatment completion in all patients in order to assess for response. A total of 19 patients with a positive result received rifaximin and repeated the breath test (7 (36.8%) males, age 56.5 ± 17.6 years). The mean peak hydrogen excretion was 13.7 ± 2.8 and 10.3 ± 7.3 ppm at baseline and following rifaximin treatment, respectively (t = 1.98, p = 0.06). LBT normalized in 8/19 (42.1%) subjects. No patients reported symptom resolution. No adverse events were reported. Strengths include the study's prospective design. Limitations include the small sample size and open label design. Rifaximin was not effective in normalizing LBT in our cohort of non-IBS subjects with symptoms suggestive of SIBO.

Intestinal permeability and Ménière's disease.

PubMed

Di Berardino, F; Zanetti, D; Ciusani, E; Caccia, C; Leoni, V; De Grazia, U; Filipponi, E; Elli, L

Ménière disease (MD) is a multifactorial chronic disabling condition characterized by episodic vertigo, ear fullness, and hearing loss. MD patients often complain of aspecific gastrointestinal symptoms associated with autonomic dysregulation, frequently outweighed by the otological manifestations. Dietary modifications have been reported to improve the typical MD symptoms in some cases. Our purpose was to test the urinary levels of lactulose and mannitol (double sugar test) and the fecal calprotectin, both markers of altered intestinal permeability, in subjects with definite MD in an active and inactive stage. Twenty-six with definite unilateral MD were studied: 14 patients were symptomatic for at least 3months with moderate to severe vertigo spells and a functional level ≥4; 12 patients had been asymptomatic (no vertigo spells) for at least 3months and had a functional level=1 at the time of testing. Twenty healthy volunteers were recruited as "control group". Lactulose and mannitol absorption was significantly increased in the symptomatic M patients compared to the asymptomatic group (p<0.02 and p<0.004, respectively) and to the controls. FC were also higher than normal only in the symptomatic group. (p<0.01). An altered intestinal permeability, according to the two assays, was found only in symptomatic MD patients. The rationale for a possible relationship between MD and intestinal permeability is forwarded. The double-sugar test and FC quantification might be implemented in the MD diagnostic workup. Copyright © 2017 Elsevier Inc. All rights reserved.

Gastric emptying of hexose sugars: role of osmolality, molecular structure and the CCK₁ receptor.

PubMed

Little, T J; Gopinath, A; Patel, E; McGlone, A; Lassman, D J; D'Amato, M; McLaughlin, J T; Thompson, D G

2010-11-01

It is widely reported that hexose sugars slow gastric emptying (GE) via osmoreceptor stimulation but this remains uncertain. We evaluated the effects of a panel of hexoses of differing molecular structure, assessing the effects of osmolality, intra-individual reproducibility and the role of the CCK(1) receptor, in the regulation of GE by hexoses. Thirty one healthy non-obese male and female subjects were studied in a series of protocols, using a (13) C-acetate breath test to evaluate GE of varying concentrations of glucose, galactose, fructose and tagatose, with water, NaCl and lactulose as controls. GE was further evaluated following the administration of a CCK(1) receptor antagonist. Three subjects underwent repeated studies to evaluate intra-individual reproducibility. At 250 mOsmol, a hexose-specific effect was apparent: tagatose slowed GE more potently than water, glucose and fructose (P < 0.05). Fructose (P < 0.05) also slowed GE, but with substantial inter-, but not intra-, individual differences. As osmolality increased further the hexose-specific differences were lost. At 500 mOsmol, all hexoses slowed GE compared with water (P < 0.05), whereas lactulose and saline did not. The slowing of GE by hexose sugars appeared to be CCK(1) receptor-dependent. The effects of hexose sugars on GE appear related to their molecular structure rather than osmolality per se, and are, at least in part, CCK(1) receptor-dependent. © 2010 Blackwell Publishing Ltd.

A method for assessing real time rates of dissolution and absorption of carbohydrate and other food matrices in human subjects.

PubMed

Lentle, R G; Sequeira, I R; Hardacre, A K; Reynolds, G

2016-06-15

We prepared pasta of differing physical dimensions but identical chemical composition that contained two monosaccharide probes (lactulose and mannitol) that are absorbed passively and promptly excreted in urine. We showed that the rates of their liberation from the pasta under simulated gastric and small intestinal conditions largely depended upon the rate of digestion of the starchy matrix. We showed, in 20 female subjects, that excretion of mannitol was slower from the pasta with the larger particle size. Hence, after consumption of either the powdered pasta or the simple solution of probe sugars, the mass of mannitol excreted between 1 and 2½ hours was greater than that excreted between 2½ and 4 hours. However these masses did not differ significantly after consumption of the pasta pellets. These differences were not reflected in the concurrent patterns of variation in either serum glucose or insulin taken over 120 minutes, their levels being similar for pasta pellets and powder with their peak values occurring synchronously during the first hour. Hence feeding test foods impregnated with lactulose and mannitol probes provided a reproducible and practical means of assessing the timing of digestion of the carbohydrate matrix and showed that this was more protracted than suggested by post prandial glucose levels. Further, the transit times calculated on a basis of the ratios of the two marker sugars could identify that the prolongation of digestion of larger particles was not accompanied by retention of digesta in particular segments of the gut.

Acute effects of carprofen and meloxicam on canine gastrointestinal permeability and mucosal absorptive capacity.

PubMed

Craven, Melanie; Chandler, Marge L; Steiner, Jörg M; Farhadi, Ashkan; Welsh, Elizabeth; Pratschke, Kathryn; Shaw, Darren J; Williams, David A

2007-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to dogs for their analgesic, antipyretic, and anti-inflammatory properties. Their beneficial actions can be offset by gastrointestinal (GI) toxicosis. Endoscopy has traditionally been employed to detect GI lesions, but alterations in GI permeability precede the development of mucosal damage. Carprofen and meloxicam alter GI permeability and mucosal absorptive capacity of dogs. Twenty adult dogs treated with an NSAID for >7 days were evaluated by permeability tests while receiving either carprofen (10 dogs) or meloxicam (10 dogs). Prospective, longitudinal observational study. A 6-sugar permeability test (sucrose, lactulose, rhamnose, 3-O-methyl-D-glucose, D-xylose, and sucralose) was performed on the day before NSAID treatment, and after 3 and 8 days of treatment. There were no significant differences in the urinary recovery ratios of lactulose: rhamnose, D-xylose: 3-O-methyl-D-glucose, or sucralose recovery within either group at any time during the study. Sucrose permeability in the meloxicam group did not alter significantly over time. However, sucrose permeability in the carprofen group decreased significantly by day 3 (P = .049) and increased again by day 8 (P = .049), to a level that was not significantly different to permeability before treatment (P = .695). The absence of increased GI permeability and diminished mucosal absorptive capacity in this group of dogs does not support the development of acute GI toxicosis during treatment with either meloxicam or carprofen.

Congenital absence of the portal vein in a cat.

PubMed

Holloway, Andrew; Groot, Louise; van der Schaaf, Klaartje

2018-01-01

A 9-month-old female neutered domestic shorthair cat presented with a history of episodic ptyalism, lethargy and abnormal behaviour. The clinical signs together with elevated pre- and post-prandial bile acid concentrations were consistent with hepatic encephalopathy (HE). In the absence of a portosystemic shunt (PSS) on abdominal ultrasound, medical management of HE was established with a protein-restricted diet and lactulose and the neurological signs resolved. Following an episode of acute vomiting and haemorrhagic diarrhoea at 19 months of age abdominal ultrasonography was repeated. The portal vein could not be demonstrated ultrasonographically; instead, portal vein tributaries were tortuous and communicated with the caudal vena cava (CdVC) at the level of the left kidney. CT angiography (CTA) confirmed the absence of the portal vein. CTA demonstrated the tortuous terminations of the portal tributaries, and several systemic veins, draining into the CdVC via a large-diameter paracaval vessel at the level of the left kidney. Gastrointestinal signs were stabilised and medical management for HE of a protein-restricted diet and lactulose was re-established. Congenital absence of the portal vein has not been described previously in the cat and should be considered in cats presenting with signs suggestive of a PSS and HE. The portal vein in the cat can be demonstrated using ultrasound, but complex congenital vascular malformations of the portal or systemic abdominal veins should be characterised using CTA and further distinguished from other vascular anomalies that may present with similar ultrasonographic features.

Efficacy and safety of laxatives for chronic constipation in long-term care settings: A systematic review.

PubMed

Alsalimy, N; Madi, L; Awaisu, A

2018-06-09

Constipation is a common disorder among long-term care (LTC) patients due to several factors. However, there are no systematic reviews investigating the use of laxatives for chronic constipation in LTC settings. This study aims to explore the safety and efficacy of laxatives in LTC patients. A systematic review of randomized controlled trials (RCTs) describing the efficacy and safety of laxatives for chronic constipation in LTC patients was conducted using the following databases and search engines: MEDLINE, Cochrane Database of Systematic Reviews, ScienceDirect, ProQuest and Google Scholar. Two of the investigators independently performed the searches, and the data were extracted using a standardized data abstraction tool. Seven RCTs involving 444 patients were included in the review. These studies included senna (with or without fibre, ie Plantago ovata), lactulose, sodium picosulphate, docusate sodium, docusate calcium, isotonic and hypotonic polyethylene glycol and Chinese herbal medicine. Senna and lactulose were the most studied laxatives in LTC patients, and senna was found to be superior to or as effective as other laxatives. Generally, the frequency and severity of adverse drug reactions (ADRs) were similar between the arms of the studies, and no serious ADRs were reported. Considering the short duration of the trials, the lack of trials including newer laxatives and the low quality of some of the included trials, the long-term efficacy and safety of these laxatives are not conclusive. There is a need to conduct more robust RCTs that include newer agents to evaluate long-term outcomes. © 2018 John Wiley & Sons Ltd.

Effects of Timing, Sex, and Age on Site-Specific Gastrointestinal Permeability Testing in Children and Adults

PubMed Central

McOmber, Mark E.; Ou, Ching-Nan; Shulman, Robert J.

2010-01-01

Summary Objectives Measurement of gastrointestinal (GI) permeability is used commonly in research and often clinically. Despite its utility, little is known about sugar excretion timeframes or the potential effects of age and gender in GI permeability testing. We sought to determine the timeframes of sugar excretion and the potential effects of age and gender on urinary recovery of the sugars. Methods Healthy adults (n=17) and children (n=15) fasted four hours after the evening meal and then ingested a solution of sucrose, lactulose, mannitol, and sucralose. Urine was collected at 30, 60, and 90 minutes after ingestion and then each time the subjects voided over the next 24 hr. Each urine void was collected separately. Results Median age for the adults was 47.5 yr. (range 21-57 yr.) and for children 10 yr. (5-17). There were no differences between children and adults in mean percent dose of sugar recovered. The time of peak urinary recovery of the sugars was generally similar between children and adults. Sucrose urinary recovery declined with age (P = 0.008; r2 = 0.19) unrelated to gender. Lactulose and sucralose urinary recovery declined with age in females (P = 0.05, r2 = 0.24 and P = 0.011, r2 = 0.41, respectively) but not in males. Conclusions Overall, sugar urinary recovery is comparable in children and adults. Specific sugar urinary recovery may change as a function of age and/or gender. These results need to be taken into account when planning and interpreting GI permeability studies. PMID:20081547

[The high fermentative capacity of colonic bacteria in the origin of flatulence and its sensibility to bismuth subsalicylate].

PubMed

León-Barúa, Raúl; Alvarez De Roig, Maritza; Roig-Arosemena, Javier; Berendson-Seminario, Roberto; Torres-Zevallos, Hernando

2007-01-01

Using a previously described technique, "in vitro" determinations were carried out for faecal fermentation (FF): basal faecal fermentation (BFF), i.e, only with faeces, with faeces and lactulose (LFF) and with faeces, lactulose and bismuth subsalicylate (BiLFF) in 34 patients with flatulence. The media+d.s. of the difference between the LFFand BFF levels (LFF-BFF) in patients with flatulence was significant and markedly higher than the respective media +d.s. in 30 normal control patients previously studied (9.1+4.7 vs. 3.9+3.2 ml gas/24 hrs; p<0.000001 respectively). And, although FF was reduced by adding bismuth salicylate in only 24% (70.6%) of the patients with flatulence but not in the remaining 10 (29.4%), in total the media+d.s. of the differences between the levels BiLFF and BFF (BiLFFBFF) was significantly lower that the media+d.s. of the differences between the LFF and BFF levels (LFF-BFF) (6.0+4.2 vs 9.1+4.7 ml gas/24 hrs; p<0.01 respectively). These results confirm that: 1) The fermentative capacity of the colonic bacteriae is most likely to be abnormally intense in peoples with flatulence and 2) Bismuth subsalicylate can be useful in the control of excessive colonic fermentation and flatulence; they raise, furthermore, the interesting possibility that we may have found the way to predict when the use of bismuth subsalicylate could be effective in the treatment of a patient with flatulence.

Intestinal Membrane Permeability and Hypersensitivity In the Irritable Bowel Syndrome

PubMed Central

Zhou, QiQi; Zhang, Buyi; Verne, G. Nicholas

2009-01-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate diarrhea-predominant IBS patients (D-IBS) that display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose / mannitol method. All subjects ingested 5 g laclulose and 2 g mannitol in 100 ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue (MVAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients have increased intestinal membrane permeability as measured by the lactulose / mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8±5.4) compared to IBS patients with normal membrane permeability and sensitivity (51.6±12.7) and controls (6.1 ± 5.6) (p<0.001). A subset of D-IBS patients have increased intestinal membrane permeability that is associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli. PMID:19595511

Effect of oligosaccharides on the adhesion of gut bacteria to human HT-29 cells.

PubMed

Altamimi, M; Abdelhay, O; Rastall, R A

2016-06-01

The influence of five oligosaccharides (cellobiose, stachyose, raffinose, lactulose and chito-oligosaccharides) on the adhesion of eight gut bacteria (Bifidobacterium bifidum ATCC 29521, Bacteroides thetaiotaomicron ATCC 29148D-5, Clostridium leptum ATCC 29065, Blautia coccoides ATCC 29236, Faecalibacterium prausnitzii ATCC 27766, Bacteroides fragilis ATCC 23745, Clostridium difficile ATCC 43255 and Lactobacillus casei ATCC 393) to mucous secreting and non-mucous secreting HT-29 human epithelial cells, was investigated. In pure culture, the bacteria showed variations in their ability to adhere to epithelial cells. The effect of oligosaccharides diminished adhesion and the presence of mucus played a major factor in adhesion, likely due to high adhesiveness to mucins present in the native human mucus layer covering the whole cell surface. However, clostridia displayed almost the same level of adhesion either with or without mucus being present. Bl. coccoides adhesion was decreased by stachyose and cellobiose in non-mucus-secreting cells in pure culture, while in mixed faecal culture cellobiose displayed the highest antiadhesive activity with an overall average of 65% inhibition amongst tested oligomers and lactulose displayed the lowest with an average of 47.4%. Bifidobacteria, Bacteroides, lactobacilli and clostridia were inhibited within the following ranges 47-78%, 32-65%, 11.7-58% and 64-85% respectively. This means that clostridia were the most strongly influenced members of the microflora amongst the bacterial groups tested in mixed culture. In conclusion, introducing oligosaccharides which are candidate prebiotics into pure or mixed cultures has affected bacterial adhesion. Copyright © 2016 Elsevier Ltd. All rights reserved.

Congenital absence of the portal vein in a cat

PubMed Central

Holloway, Andrew; Groot, Louise; van der Schaaf, Klaartje

2018-01-01

Case summary A 9-month-old female neutered domestic shorthair cat presented with a history of episodic ptyalism, lethargy and abnormal behaviour. The clinical signs together with elevated pre- and post-prandial bile acid concentrations were consistent with hepatic encephalopathy (HE). In the absence of a portosystemic shunt (PSS) on abdominal ultrasound, medical management of HE was established with a protein-restricted diet and lactulose and the neurological signs resolved. Following an episode of acute vomiting and haemorrhagic diarrhoea at 19 months of age abdominal ultrasonography was repeated. The portal vein could not be demonstrated ultrasonographically; instead, portal vein tributaries were tortuous and communicated with the caudal vena cava (CdVC) at the level of the left kidney. CT angiography (CTA) confirmed the absence of the portal vein. CTA demonstrated the tortuous terminations of the portal tributaries, and several systemic veins, draining into the CdVC via a large-diameter paracaval vessel at the level of the left kidney. Gastrointestinal signs were stabilised and medical management for HE of a protein-restricted diet and lactulose was re-established. Relevance and novel information Congenital absence of the portal vein has not been described previously in the cat and should be considered in cats presenting with signs suggestive of a PSS and HE. The portal vein in the cat can be demonstrated using ultrasound, but complex congenital vascular malformations of the portal or systemic abdominal veins should be characterised using CTA and further distinguished from other vascular anomalies that may present with similar ultrasonographic features. PMID:29372068

MLCK-mediated intestinal permeability promotes immune activation and visceral hypersensitivity in PI-IBS mice.

PubMed

Long, Y; Du, L; Kim, J J; Chen, B; Zhu, Y; Zhang, Y; Yao, S; He, H; Zheng, X; Huang, Z; Dai, N

2018-04-11

Alterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI-IBS) mouse model. Trichinella spiralis-infected PI-IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens-1) and MLCK-associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension. Eight weeks after inoculation with T. spiralis, PI-IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens-1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI-IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1-dominant immune profile in PI-IBS mice. MLCK is a pivotal step in inducing increased intestinal permeability promoting low-grade intestinal immune activation and visceral hypersensitivity in PI-IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS. © 2018 John Wiley & Sons Ltd.

Further Concerns About Glutamine: A Case Report on Hyperammonemic Encephalopathy.

PubMed

Cioccari, Luca; Gautschi, Matthias; Etter, Reto; Weck, Anja; Takala, Jukka

2015-10-01

We report a case of a woman with hyperammonemic encephalopathy following glutamine supplementation. Case report. Plasma amino acid analysis suggestive of a urea cycle defect and initiation of a treatment with lactulose and the two ammonia scavenger drugs sodium benzoate and phenylacetate. Together with a restricted protein intake ammonia and glutamine plasma levels decreased with subsequent improvement of the neurological status. Massive catabolism and exogenous glutamine administration may have contributed to hyperammonemia and hyperglutaminemia in this patient. This case adds further concerns regarding glutamine administration to critically ill patients and implies the importance of monitoring ammonia and glutamine serum levels in such patients.

CoMiniGut—a small volume in vitro colon model for the screening of gut microbial fermentation processes

PubMed Central

Khakimov, Bekzod; Nielsen, Sebastian; Sørensen, Helena; van den Berg, Frans; Nielsen, Dennis Sandris

2018-01-01

Driven by the growing recognition of the influence of the gut microbiota (GM) on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v). We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs) were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative abundance of

CoMiniGut-a small volume in vitro colon model for the screening of gut microbial fermentation processes.

PubMed

Wiese, Maria; Khakimov, Bekzod; Nielsen, Sebastian; Sørensen, Helena; van den Berg, Frans; Nielsen, Dennis Sandris

2018-01-01

Driven by the growing recognition of the influence of the gut microbiota (GM) on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v). We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs) were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative abundance of

Acute Effects of a Glucagon-Like Peptide 2 Analogue, Teduglutide, on Gastrointestinal Motor Function and Permeability in Adult Patients With Short Bowel Syndrome on Home Parenteral Nutrition.

PubMed

Iturrino, Johanna; Camilleri, Michael; Acosta, Andres; O'Neill, Jessica; Burton, Duane; Edakkanambeth Varayil, Jithinraj; Carlson, Paula J; Zinsmeister, Alan R; Hurt, Ryan

2016-11-01

Glucagon-like peptide 2 (GLP-2) agonists decrease the need for parenteral nutrition (PN) in short bowel syndrome (SBS); mechanisms evaluated to date have focused on the intestinotrophic effect of GLP-2 agonists such as increased absorptive capacity of the remnant intestine and increased citrulline levels. Other mechanisms may also play a role in effects of GLP-2 agonists. To measure effects of a GLP-2 agonist, teduglutide (TED), compared with placebo (PLA) on gastric emptying (GE), overall gut transit, fluid balance, intestinal monosaccharide absorption, and permeability in patients with SBS on home PN (HPN). In 8 adults with SBS on HPN, we compared daily subcutaneous TED (0.05 mg/kg) and PLA (crossover design, each treatment 7 days with a 14-day washout) on gut transit, intestinal absorption, and permeability after oral mannitol (200 mg) and lactulose (1 g), as well as stool weight and urine volume over 8 hours. Analysis used the paired t test. Of 8 patients, 4 were men, with a mean ± SD age of 54 ± 1 years, body mass index of 25 ± 4 kg/m 2 , residual small intestine of 63 ± 12 cm, and 25% ± 15% of residual colon. The overall gut transit (% emptied at 6 hours) was 53.4% ± 15% for TED vs 62.4% ± 15.2% for PLA (P = .075), with no effect on GE (P = .74). TED increased urine mannitol excretion at 0-2 hours (16.2 ± 3.6 mg TED vs 11.3 ± 2.2 mg PLA, P = .20) and 0-8 hours (32.7 ± 5.9 mg PLA vs 48.8 ± 8.9 mg TED, P = .17). There were no differences in urine lactulose excretion or lactulose/mannitol ratio (0.024 ± 0.005 TED vs 0.021 ± 0.005 PLA). Over 8 hours, TED (vs PLA) numerically reduced stool weight (mean ± SEM, 77 ± 18 g TED vs 106 ± 43 g PLA, P = .42) and increased urine volume (408.9 ± 52.2 mL TED vs 365.7 ± 57.3 mL PLA, P = .34). Seven-day TED treatment in 8 participants suggests beneficial effects on fluid balance and monosaccharide absorption, and it retarded overall gut transit with no effects on GE or mucosal permeability. Larger, longer

Influence of thermally oxidized vegetable oils and animal fats on intestinal barrier function and immune variables in young pigs.

PubMed

Liu, P; Kerr, B J; Weber, T E; Chen, C; Johnston, L J; Shurson, G C

2014-07-01

To evaluate the effect of feeding thermally oxidized lipids on metabolic oxidative status, gut barrier function, and immune response of young pigs, 108 barrows (6.67 ± 0.03 kg BW) were assigned to 12 dietary treatments in a 4 × 3 factorial arrangement in addition to a corn-soybean meal control diet. Main effects were 4 lipid sources (corn oil [CN], canola oil [CA], poultry fat [PF], and tallow [TL]) and 3 oxidation levels (original lipids [OL], slow oxidation [SO] of lipids heated for 72 h at 95°C, or rapid oxidation [RO] of lipids heated for 7 h at 185°C). Pigs were provided ad libitum access to diets for 28 d followed by controlled feed intake for 10 d. After a 24-h fast on d 38, serum was collected and analyzed for α-tocopherol (α-T), thiobarbituric acid reactive substances (TBARS), endotoxin, haptoglobin, IgA, and IgG. On the same day following serum collection, lactulose and mannitol were fed and subsequently measured in the urine to evaluate gut permeability. There was a source × peroxidation interaction for serum α-T concentration where pigs fed SO or RO had decreased (P < 0.05) serum α-T concentration compared with pigs fed OL in CA and CN diets but not in pigs fed PF and TL diets. There was no source × peroxidation interaction for serum TBARS, but among all lipid sources, pigs fed SO or RO lipids had increased (P < 0.05) serum TBARS compared with pigs fed OL. In addition, pigs fed CN or CA had greater (P < 0.05) serum TBARS compared with pigs fed PF or TL diets. There were no lipid source × peroxidation level interaction or lipid source or peroxidation level effects on serum endotoxin, haptoglobin, IgA, or IgG. Pigs fed lipid supplemented diets tended to have increased serum endotoxin (P = 0.06), IgA (P = 0.10), and IgG (P = 0.09) compared with pigs fed the control diet. There were no lipid source × peroxidation level interaction or lipid source or peroxidation level effects on urinary TBARS and lactulose to mannitol ratio. Compared with pigs

Digestibility of carbohydrates from rice-, oat- and wheat-based ready-to-eat breakfast cereals in children.

PubMed

Brighenti, F; Casiraghi, M C; Ciappellano, S; Crovetti, R; Testolin, G

1994-09-01

To study the effect of the presence and quality of dietary fibre in ready-to-eat (RTE) breakfast cereals on completeness of carbohydrate digestion in children and on starch susceptibility to alpha-amylase in vitro. A controlled intervention study. Eight 3-8-year-old healthy children. Completeness of digestion was evaluated by assessing the amount of carbohydrates apparently fermented into the colon using the breath-H2 technique after consumption in random order, of five breakfast tests containing boiled rice (either alone or supplemented with 3 g of lactulose) as reference food, or RTE cereals based on rice (low-fibre), wheat (high insoluble fibre) and oats (high-soluble fibre). The potential glycaemic impact of the products was estimated in vitro by assessing starch susceptibility to alpha-amylolysis using an enzymatic-dialysis method. Compared to boiled rice and to rice-based RTE cereal, wheat- and oat-based RTE cereals both significantly (P < 0.05) increased the amount of apparently fermented carbohydrates (+1.1 +/- 1.7% of total breakfast carbohydrate fermented for rice, +5.6 +/- 0.9% for wheat and +9.4 +/- 3.7% for oats; mean +/- SEM), calculated using the excess H2 in breath after lactulose as standard. All products showed similar in vitro digestibility, resulting in estimated glycaemic indexes of 117.5 (24.0) for rice, and 105.7 (14.1) for oats-based, 128.4 (17.6) for wheat-based, and 129.8 (16.6) [mean 95% CI)] for rice-based RTE cereals. Results suggest that the presence of fibre in RTE breakfast cereals, in particular soluble fibre, increases colonic fermentation in children whereas it seems not to affect glucose availability.

Effect of dual-type oligosaccharides on constipation in loperamide-treated rats

PubMed Central

Han, Sung Hee; Hong, Ki Bae; Kim, Eun Young; Ahn, So Hyun

2016-01-01

BACKGROUND/OBJECTIVES Constipation is a condition that can result from intestinal deformation. Because humans have an upright posture, the effects of gravity can cause this shape deformation. Oligosaccharides are common prebiotics and their effects on bowel health are well known. However, studies of the physiological functionality of a product that contains both lactulose and galactooligosaccharides are insufficient. We investigated the constipation reduction effect of a dual-type oligosaccharide, Dual-Oligo, in loperamide-treated rats. MATERIALS/METHODS Dual-Oligo consists of galactooligosaccharides (15.80%) and lactulose (51.67%). Animals were randomly divided into four groups, the normal group (normal), control group (control), low concentration of Dual-Oligo (LDO) group, and high concentration of Dual-Oligo (HDO) group. After 7 days of oral administration, fecal pellet amount, fecal weight, water content of fecal were measured. Blood chemistry, short-chain fatty acid (SCFA), gastrointestinal transit ratio and length and intestinal mucosa were analyzed. RESULTS Dual-Oligo increased the fecal weight, and water content of feces in rats with loperamide-induced constipation. Gastrointestinal transit ratio and length and area of intestinal mucosa significantly increased after treatment with Dual-Oligo in loperamide-induced rats. A high concentration of Dual-Oligo tended to produce more acetic acid than that observed for the control group, and Dual-Oligo affected the production of total SCFA. Bifidobacteria concentration of cecal contents in the high-concentration oligosaccharide (HDO) and low-concentration oligosaccharide (LDO) groups was similar to the result of the normal group. CONCLUSIONS These results showed that Dual-Oligo is a functional material that is derived from a natural food product and is effective in ameliorating constipation. PMID:27909555

Double-blind randomized controlled trial of rifaximin for persistent symptoms in patients with celiac disease.

PubMed

Chang, Matthew S; Minaya, Maria T; Cheng, Jianfeng; Connor, Bradley A; Lewis, Suzanne K; Green, Peter H R

2011-10-01

Small intestinal bacterial overgrowth (SIBO) is one cause of a poor response to a gluten-free diet (GFD) and persistent symptoms in celiac disease. Rifaximin has been reported to improve symptoms in non-controlled trials. To determine the effect of rifaximin on gastrointestinal symptoms and lactulose-hydrogen breath tests in patients with poorly responsive celiac disease. A single-center, double-blind, randomized, controlled trial of patients with biopsy-proven celiac disease and persistent gastrointestinal symptoms despite a GFD was conducted. Patients were randomized to placebo (n = 25) or rifaximin (n = 25) 1,200 mg daily for 10 days. They completed the Gastrointestinal Symptom Rating Scale (GSRS) and underwent lactulose-hydrogen breath tests at weeks 0, 2, and 12. An abnormal breath test was defined as: (1) a rise in hydrogen of ≥20 parts per million (ppm) within 100 min, or (2) two peaks ≥20 ppm over baseline. GSRS scores were unaffected by treatment with rifaximin, regardless of baseline breath tests. In a multivariable regression model, the duration of patients' gastrointestinal symptoms significantly predicted their overall GSRS scores (estimate 0.029, p < 0.006). According to criteria 1 and 2, respectively, SIBO was present in 55 and 8% of patients at baseline, intermittently present in 28 and 20% given placebo, and 28 and 12% given rifaximin. There was no difference in the prevalence of SIBO between placebo and treatment groups at weeks 2 and 12. Rifaximin does not improve patients' reporting of gastrointestinal symptoms and hydrogen breath tests do not reliably identify who will respond to antibiotic therapy.

Dietary management of acute diarrhoea in children: effect of fermented and amylase-digested weaning foods on intestinal permeability.

PubMed

Willumsen, J F; Darling, J C; Kitundu, J A; Kingamkono, R R; Msengi, A E; Mduma, B; Sullivan, K R; Tomkins, A M

1997-03-01

There is a strong relationship between diarrhoea, malnutrition, and intestinal integrity. To investigate the effect of different dietary-treatment on intestinal permeability during acute diarrhoea, 87 Tanzanian children aged 6-25 months were recruited to this study when admitted to hospital. Children with acute diarrhoea were rehydrated and then randomly assigned to one of three dietary treatment groups: a conventional low-energy density porridge, a high-energy density amylase digested porridge (AMD), or a high-energy density amylase digested and then fermented porridge (FAD). Lactulose/mannitol permeability tests were performed on admission, at 3 days, and at follow-up 2 and 4 weeks after discharge. The lactulose/mannitol (L/M) ratios were compared between dietary treatment groups and to a group of age-matched, healthy control subjects. Children with diarrhoea had higher L/M ratios (geometric mean 0.85, 95% CI 0.68-1.05) compared with control subjects (0.14, 0.12-0.17) on admission. There was a significant difference in the change in L/M ratio between admission and 3 days between dietary treatment groups in favour of the FAD group (p < 0.05). Dietary treatment and intestinal damage at admission explain 13.5% of the variation in L/M ratio, but when age at admission and age at weaning are included as covariants, 21.9% is explained. FAD porridge seems to be more effective in the treatment of intestinal permeability than AMD or conventional porridge. Urinary lactose concentrations in spot urine samples taken prior to the permeability test were also measured. There was a significant correlation with the L/M ratio (correlation coefficient = 0.62, p < 0.001).

Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

PubMed Central

Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

2015-01-01

Background/Aims This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Methods Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. Results The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. Conclusions There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability. PMID:25717051

Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis.

PubMed

Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

2015-11-23

This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.

[No inhibition of intestinal motility following ketamine-midazolam anesthesia. A comparison of anesthesia with enflurane and fentanyl/midazolam].

PubMed

Freye, E; Knüfermann, V

1994-02-01

Postoperative intestinal atonia is a complication which is likely to occur in patients predisposed for constipation and in patients after intra-abdominal operations. The postoperative delay of bowel movement, however, is often also related to the type of anaesthesia being used. In order to evaluate the magnitude of an anaesthetic-induced postoperative delay of bowel movement, two types of intravenous-based anaesthesia using fentanyl/midazolam (1 mg/25 mg; dosage 0.1 ml/kg/h), and ketamine/midazolam (250 mg/25 mg; dosage 0.1 ml/kg/h) respectively were compared with a volatile anaesthetic technique (enflurane; mean concentration 1.5 vol%). METHODS. In three groups of patients (each n = 15) undergoing elective surgery of the lower extremities, induction of anaesthesia was accomplished with methohexital (1-1.5 mg/kg) to facilitate intubation. For the maintenance of muscle relaxation vecuronium bromide was used. All patients were given droperidol to prevent postoperative emesis, and they were artificially ventilated with N2O/O2 (60:40) to normal end-expiratory CO2 concentrations. No anticholinergic agents were used at the end of operation since they are known to interfere with bowel motility. In order to determine gastro-intestinal motility, the H2 exhalation test was used. For this purpose 40 g lactulose in 100 ml of water was given to all patients via a gastral tube shortly before extubation. Lactulose is broken down by bacteria once it enters the colon, and H2 is released, taken up by the vascular system and exhaled. Postoperatively, patients were asked to exhale into a 20-ml syringe every 10 min. The content was analysed for hydrogen (ppm), using an electrochemical sensor (GMI exhaled hydrogen monitor). From the time of lactulose instillation to a threefold increase in end-expiratory hydrogen concentration (compared to the preoperative value), gastro-coecal transit time was computed. RESULTS. All three groups of patients were comparable in age, height and body

Novel analytical approach to a multi-sugar whole gut permeability assay.

PubMed

van Wijck, Kim; van Eijk, Hans M H; Buurman, Wim A; Dejong, Cornelis H C; Lenaerts, Kaatje

2011-09-15

Many pathophysiological conditions are associated with increased gastrointestinal permeability, reflecting an elevated risk of endotoxaemia, inflammation, and sepsis. Permeability tests are increasingly used in clinical practice to obtain information on gastrointestinal functioning, but tests are often restricted to the small intestine, and require large oral sugar doses. Therefore, a novel multi-sugar assay was developed, allowing assessment of whole gut permeability changes in urinary and plasma samples collected at regular intervals from 10 healthy volunteers at baseline and after intake of monosaccharides (rhamnose and erythritol) and disaccharides (sucrose, lactulose, and sucralose). Samples were analyzed by isocratic cation-exchange LC-MS. Sample preparation and detection conditions were optimized. After centrifugation, chromatographic separation was achieved on an IOA-1000 column set at 30°C. Column effluent was mixed with ammonia for sugar-ammonium adduct formation. The lower limit of detection was 0.05 μmol/L for disaccharides and 0.1 μmol/L for monosaccharides. Linearity for each probe was between 1 and 1000 μmol/L (R(2): 0.9987-0.9999). Coefficients of variation were <5% in urine, and <9% in plasma. Recovery data were within the 90% to 110% range at all spiked concentrations. This highly sensitive novel LC-MS approach resulted in a significant decrease of the detection limit for all sugar probes, allowing a 5-fold reduction of the commonly used lactulose dose and the addition of sugar probes to also assess the gastroduodenal and colon permeability. In combination with its extended application in plasma, these features make the novel assay a promising tool in the assessment of site-specific changes in gastrointestinal permeability in clinical practice. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of different monosaccharides and disaccharides on boar sperm quality after cryopreservation.

PubMed

Gómez-Fernández, José; Gómez-Izquierdo, Emilio; Tomás, Cristina; Mocé, Eva; de Mercado, Eduardo

2012-07-01

The aim of the present study was to evaluate the cryoprotectant effect of different non-permeating sugars for boar sperm. Pooled semen from three boars was used for the experiments. In the first experiment, the sperm quality of boar sperm cryopreserved with an egg-yolk based extender supplemented with different monosaccharides (glucose, galactose or fructose) was compared to a control cryopreserved in lactose-egg yolk extender. In the second experiment, the effect of five disaccharides (lactose, sucrose, lactulose, trehalose or melibiose) on boar sperm cryosurvival was studied. Several sperm quality parameters were assessed by flow cytometry in samples incubated for 30 and 150 min at 37°C after thawing: percentages of sperm with intact plasma membrane (SIPM), sperm presenting high plasma membrane fluidity (HPMF), sperm with intracellular reactive oxygen substances production (IROSP) and apoptotic sperm (AS). In addition, the percentages of total motile (TMS) and progressively motile sperm (PMS) were assessed at the same incubation times with a computer-assisted sperm analysis system. Freezing extenders supplemented with each of the monosaccharide presented smaller cryoprotective effect than the control extender supplemented with lactose (P<0.05). However, from the three monosaccharides tested, glucose provided the best sperm quality after freezing-thawing. With respect to the disaccharides studied, samples frozen with the extender supplemented with lactulose exhibited in general the lowest sperm quality, except for the percentage of capacitated sperm, which was highest (P<0.05) in the samples cryopreserved with the trehalose extender. Our results suggest that disaccharides have higher cryoprotective effect than monosaccharides, although the monosaccharide composition of the disaccharides is also important, since the best results were obtained with those disaccharides presenting glucose in their composition. Copyright © 2012 Elsevier B.V. All rights reserved.

Small intestinal permeability in patients with eosinophilic oesophagitis during active phase and remission.

PubMed

Katzka, David A; Geno, Debra M; Blair, Hilary E; Lamsam, Jesse L; Alexander, Jeffrey A; Camilleri, Michael

2015-04-01

Eosinophilic oesophagitis (EoE) is presumed to be an isolated oesophageal disease; yet other allergic diseases associated with eosinophilic infiltration of target tissues, such as asthma and eczema, show perturbed functions of other sites that may be involved in the diathesis of allergy modulation. To analyse small intestinal permeability in patients with active EoE and in a separate group of patients in remission. Small bowel permeability was determined using a dual sugar method by calculating lactulose:mannitol (L:M) ratio in 17 patients who met consensus criteria for active EoE (>15 eos/HPF) and 8 patients in remission (<5 eos/HPF). Data from 28 healthy controls was used for comparison. Patients with active EoE had significantly higher L:M ratios when compared to controls (0.045 vs. 0.033, p<0.001) and to EoE in remission (0.041 vs. 0.027, p<.001). There was no significant difference in L:M between the group with EoEin remission and healthy controls. The current data show that L:M ratio of 0.033 also provides a reasonable cut-off that defined the active EoE group compared to patients in remission. The main component explaining the change in L:M ratio was increased absorption (and excretion) of lactulose ((1601 ± 106 ug) when compared to the EoE remission (969 ± 91 ug) and control (1043 ± 92 ug, p<.001) groups. Small bowel permeability is overall increased in patients with active EoE, and is normal in patients with EoE in remission when compared to healthy controls. The role of the small bowel in active EoE deserves further investigation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

β-galactosidase from Aspergillus lacticoffeatus: A promising biocatalyst for the synthesis of novel prebiotics.

PubMed

Cardoso, Beatriz B; Silvério, Sara C; Abrunhosa, Luís; Teixeira, José A; Rodrigues, Lígia R

2017-09-18

β-galactosidase (EC 3.2.1.23) are interesting enzymes able to catalyze lactose hydrolysis and transfer reactions to produce lactose-based prebiotics with potential application in the pharmaceutical and food industry. In this work, Aspergillus lacticoffeatus is described, for the first time, as an effective β-galactosidase producer. The extracellular enzyme production was evaluated in synthetic and alternative media containing cheese whey and corn steep liquor. Although β-galactosidase production occurred in all media (expect for the one composed solely by cheese whey), the highest enzymatic activity values (460U/mL) were obtained for the synthetic medium. Ochratoxin A production in synthetic medium was also evaluated and 9days of fermentation was identified as a suitable fermentation time to obtain a crude extract enzyme with mycotoxin concentration below the legal comparable value established for wine and grape juices (2ng/mL). The optimal pH and temperature for the crude extract enzyme was found in the range of 3.5-4.5 and 50-60°C, respectively. The β-galactosidase activity was reduced in the presence of Ba 2+ , Fe 2+ , Li + , K + and galactose, while additives (except for ascorbic acid) and detergents exhibited a positive effect on enzymatic activity. This enzyme was able to catalyze the synthesis of prebiotics, namely lactulose (2.5g/L) and a galacto-oligosaccharide (trisaccharide, 6.3g/L), either when whole cells or crude enzyme was used as biocatalyst. The lactulose production using fungal whole cells is herein reported for the first time. Additionally, A. lacticoffeatus was also found to produce an enzyme with fructosyltransferase activity and other prebiotics, namely fructo-oligosaccharide 1-kestose (2.4g/L). Copyright © 2017 Elsevier B.V. All rights reserved.

A double-blind, placebo-controlled, glutamine-supplementation trial in growth-faltering Gambian infants.

PubMed

Williams, Elizabeth A; Elia, Marinos; Lunn, Peter G

2007-08-01

Growth faltering during infancy is a characteristic of life in developing countries. Previous studies have shown that small-intestine mucosal enteropathy, accompanied by endotoxemia and a persistent systemic inflammatory response, accounts for up to 64% of the growth faltering in Gambian infants. The objective was to test whether glutamine, with its putative trophic effects on enterocytes, immune cells, and intestinal integrity, can accelerate the repair of the intestine, lower immunostimulation, and reduce growth faltering. Ninety-three infants aged 4-10 mo from the West Kiang region of The Gambia were studied in a double-blind, double-placebo, controlled trial. Glutamine (0.25 mg/kg body wt) or a placebo that contained an isonitrogenous, isoenergetic mix of nonessential amino acids was orally administered twice daily throughout the 5-mo rainy season. Anthropometric measurements were made monthly during the supplementation period and for 6 mo after supplementation. Intestinal permeability was measured monthly (by determining the ratio of lactulose to mannitol), and finger-prick blood samples were collected for the analysis of plasma proteins on 3 occasions. Gambian infants showed a seasonal deterioration in growth and persistently elevated acute phase protein concentrations and intestinal permeability. Oral supplementation with glutamine did not improve growth (x +/- SE: weight gain, 60 +/- 19 and 69 +/- 20 g/mo; length gain, 1.01 +/- 0.05 and 0.95 +/- 0.03 cm/mo) or intestinal permeability [lactulose:mannitol ratio: 0.29 (95% CI: 0.23, 0.35) and 0.26 (95% CI: 0.21, 0.32)] in the glutamine and placebo groups, respectively. It also had no effect on infant morbidity or on plasma concentrations of immunoglobulins or acute phase proteins. Glutamine supplementation failed to improve growth or intestinal status in malnourished Gambian infants.

Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis.

PubMed

Kim, Dae Bum; Paik, Chang-Nyol; Sung, Hea Jung; Chung, Woo Chul; Lee, Kang-Moon; Yang, Jin-Mo; Choi, Myung-Gyu

2015-01-01

The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis. 36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H2)-methane (CH4) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H2 (≥20 ppm) or CH4 (≥10 ppm) over the baseline or (2) a baseline H2 (≥20 ppm) or CH4 (≥10 ppm) within 90 min after lactulose load. LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H2 levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H2)+, (CH4)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT- group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT- group The laboratory and radiologic features were not significantly different between LBT+ and LBT- groups. SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H2 and CH4 appear to be related with deterioration of intestinal symptoms. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh.

PubMed

Campbell, Rebecca K; Schulze, Kerry J; Shaikh, Saijuddin; Mehra, Sucheta; Ali, Hasmot; Wu, Lee; Raqib, Rubhana; Baker, Sarah; Labrique, Alain; West, Keith P; Christian, Parul

2017-07-01

Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. EED prevalence (L:M > 0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or α-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and α-1 antitrypsin (r = 0.33, P < 0.01), and biomarker values did not differ by supplementation history. A 1-factor partial least squares model with L:M as the dependent variable explained only 8.6% of L:M variability. In adjusted models, L:M was associated with child sex and socioeconomic status index, whereas systemic inflammation was predicted mainly by recent illness, not EED. Impaired intestinal health is widespread in this setting of prevalent stunting, but a panel of serum and stool biomarkers demonstrated poor agreement with L:M. Etiologies of intestinal and systemic inflammation are likely numerous and complex in resource-poor settings, underscoring the need for a better case definition with corresponding diagnostic methods to further the study of EED.

Management of chronic constipation in patients with diabetes mellitus.

PubMed

Prasad, V G M; Abraham, Philip

2017-01-01

The aim of this review is to provide an overview of the clinical assessment and evidence-based treatment options for managing diabetes-associated chronic constipation. A literature search of published medical reports in English language was performed using the OVID Portal, from PUBMED and the Cochrane Database of Systematic Reviews, from inception to October 2015. A total of 145 abstracts were identified; duplicate publications were removed and 95 relevant full-text articles were retrieved for potential inclusion. Chronic constipation is one of the most common gastrointestinal symptoms in patients with diabetes, and occurs more frequently than in healthy individuals. Treatment goals include improving symptoms and restoring bowel function by accelerating colonic transit and facilitating defecation. Based on guidelines and data from published literature, food and dietary change with exercise and lifestyle change should be the first step in management. For patients recalcitrant to these changes, laxatives should be the next step of treatment. Treatment should begin with bulking agents such as psyllium, bran or methylcellulose followed by osmotic laxatives if response is poor. Lactulose, polyethylene glycol and lactitol are the most frequently prescribed osmotic agents. Lactulose has a prebiotic effect and a carry-over effect (continued laxative effect for at least 6 to 7 days, post cessation of treatment). Stimulants such as bisacodyl, sodium picosulphate and senna are indicated if osmotic laxatives are not effective. Newer agents such as chloride-channel activators and 5-HT4 agonist can be considered for severe or resistant cases. The primary aim of intervention in diabetic patients with chronic constipation is to better manage the diabetes along with management of constipation. The physician should explain the rationale for prescribing laxatives and educate patients about the potential drawbacks of long-term use of laxatives. They should contact their physician if

Sieving characteristics of cytokine- and peroxide-induced epithelial barrier leak: Inhibition by berberine

PubMed Central

DiGuilio, Katherine M; Mercogliano, Christina M; Born, Jillian; Ferraro, Brendan; To, Julie; Mixson, Brittany; Smith, Allison; Valenzano, Mary Carmen; Mullin, James M

2016-01-01

AIM: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak. METHODS: We examined the effects of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1-β (IL1β) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of CACO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of 14C-D-mannitol, 3H-Lactulose and 14C-Polyethylene glycol as radiolabeled probe molecules. The isoquinoline alkaloid, berberine, was then examined for its ability to reduce specific types of transepithelial leak. RESULTS: Exposure to TNF-α alone (200 ng/mL; 48 h) induced a 50% decrease in TER, i.e., increased leak of Na+ and Cl- - with only a marginal but statistically significant increase in transepithelial leak of 14C-mannitol (Jm). Exposure to TNF-α + IFN-γ (200 ng/mL; 48 h) + IL1β (50 ng/mL; 48 h) did not increase the TER change (from TNF-α alone), but there was now a 100% increase in Jm. There however was no increase in transepithelial leak of two larger probe molecules, 3H-lactulose and 14C-polyethylene glycol (PEG). However, exposure to TNF-α + IFN-γ + IL1β followed by a 5 h exposure to 2 mmol/L H2O2 resulted in a 500% increase in 14C-PEG leak as well as leak to the luminal mitogen, epidermal growth factor. CONCLUSION: This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances. PMID:27190695

Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms.

PubMed

Pugh, Jamie N; Impey, Samuel G; Doran, Dominic A; Fleming, Simon C; Morton, James P; Close, Graeme L

2017-09-01

The purpose of this study was to investigate the effects of high-intensity interval running on markers of gastrointestinal (GI) damage and permeability alongside subjective symptoms of GI discomfort. Eleven male runners completed an acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at 120% maximal oxygen uptake) where markers of GI permeability, intestinal damage, and GI discomfort symptoms were assessed and compared with resting conditions. Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio (0.051 ± 0.016 vs. 0.031 ± 0.021, p = 0.0047; 95% confidence interval (CI) = 0.006 to 0.036) and sucrose concentrations (0.388 ± 0.217 vs. 0.137 ± 0.148 mg·L -1 ; p < 0.001; 95% CI = 0.152 to 0.350). In contrast, urinary lactulose/rhamnose (0.032 ± 0.005 vs. 0.030 ± 0.005; p = 0.3; 95% CI = -0.012 to 0.009) or sucrose concentrations (0.169% ± 0.168% vs. 0.123% ± 0.120%; p = 0.54; 95% CI = -0.199 to 0.108) did not differ between HIIT and resting conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was significantly increased (p < 0.001) during and in the recovery period from HIIT whereas no changes were observed during rest. Mild symptoms of GI discomfort were reported immediately and at 24 h post-HIIT, although these symptoms did not correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI permeability and intestinal I-FABP release, although these do not correlate with symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data showing that it is possible to detect changes in intestinal permeability that is not observed using urinary sampling over a shorter time-period.

The Effects of Probiotics and Symbiotics on Risk Factors for Hepatic Encephalopathy: A Systematic Review.

PubMed

Viramontes Hörner, Daniela; Avery, Amanda; Stow, Ruth

2017-04-01

Alterations in the levels of intestinal microbiota, endotoxemia, and inflammation are novel areas of interest in the pathogenesis of hepatic encephalopathy (HE). Probiotics and symbiotics are a promising treatment option for HE due to possible beneficial effects in modulating gut microflora and might be better tolerated and more cost-effective than the traditional treatment with lactulose, rifaximin or L-ornithine-L-aspartate. A systematic search of the electronic databases PubMed, ISI Web of Science, EMBASE, and Cochrane Library was conducted for randomized controlled clinical trials in adult patients with cirrhosis, evaluating the effect of probiotics and symbiotics in changes on intestinal microflora, reduction of endotoxemia, inflammation, and ammonia, reversal of minimal hepatic encephalopathy (MHE), prevention of overt hepatic encephalopathy (OHE), and improvement of quality of life. Nineteen trials met the inclusion criteria. Probiotics and symbiotics increased beneficial microflora and decreased pathogenic bacteria and endotoxemia compared with placebo/no treatment, but no effect was observed on inflammation. Probiotics significantly reversed MHE [risk ratio, 1.53; 95% confidence interval (CI): 1.14, 2.05; P=0.005] and reduced OHE development (risk ratio, 0.62; 95% CI: 0.48, 0.80; P=0.0002) compared with placebo/no treatment. Symbiotics significantly decreased ammonia levels compared with placebo (15.24; 95% CI: -26.01, -4.47; P=0.006). Probiotics did not show any additional benefit on reversal of MHE and prevention of OHE development when compared with lactulose, rifaximin, and L-ornithine-L-aspartate. Only 5 trials considered tolerance with minimal side effects reported. Although further research is warranted, probiotics and symbiotics should be considered as an alternative therapy for the treatment and management of HE given the results reported in this systematic review.

Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation1

PubMed Central

Wessells, K. Ryan; Hess, Sonja Y.; Rouamba, Noel; Ouédraogo, Zinewendé P.; Kellogg, Mark; Goto, Rie; Duggan, Christopher; Ouédraogo, Jean-Bosco; Brown, Kenneth H.

2015-01-01

Objectives Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12 and folate; however, little information is available on mineral absorption. We therefore investigated the relationship between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc absorption, as estimated by the change in plasma zinc concentration (PZC) following short-term zinc or placebo supplementation. Methods We conducted a randomized, partially-masked, placebo-controlled trial among 282 apparently healthy children 6–23 mo of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg zinc, as zinc sulfate, or placebo, daily for 21 d. Results At baseline, mean ± SD PZC was 62.9 ± 11.9 µg/dL; median (IQR) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentration were 0.04 (0.03 – 0.07) and 11.4 (9.0 – 15.6) µmol/L, respectively. Change in PZC was significantly greater in the zinc supplemented versus placebo group (15.6 ± 13.3 µg/dL vs. 0.02 ± 10.9 µg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (−1.1 µg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relationship did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC. Conclusions Although altered intestinal permeability may reduce dietary zinc absorption, it likely does not undermine the efficacy of zinc supplementation, given the large increases in PZC following short-term zinc supplementation observed in this study, even among those with increased urinary L:M recovery ratios. PMID:23689263

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

PubMed

Mujagic, Z; Ludidi, S; Keszthelyi, D; Hesselink, M A M; Kruimel, J W; Lenaerts, K; Hanssen, N M J; Conchillo, J M; Jonkers, D M A E; Masclee, A A M

2014-08-01

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS. © 2014 John Wiley & Sons Ltd.

Pharmacotherapy for hepatic encephalopathy.

PubMed

Phongsamran, Paula V; Kim, Jiwon W; Cupo Abbott, Jennifer; Rosenblatt, Angela

2010-06-18

Hepatic encephalopathy (HE) is a challenging clinical complication of liver dysfunction with a wide spectrum of neuropsychiatric abnormalities that range from mild disturbances in cognitive function and consciousness to coma and death. The pathogenesis of HE in cirrhosis is complex and multifactorial, but a key role is thought to be played by circulating gut-derived toxins of the nitrogenous compounds, most notably ammonia. Therapeutic treatment options for HE are currently limited and have appreciable risks and benefits associated with their use. Management of HE primarily involves avoidance of precipitating factors, limitation of dietary protein intake, and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and select antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. However, multiple adverse events have been associated with their use. In addition, recent literature has questioned the true efficacy of the disaccharides for this indication. Neomycin, metronidazole and vancomycin may be used as alternative treatments for patients intolerant or unresponsive to non-absorbable disaccharides. Antimicrobials reduce bacterial production of ammonia and other bacteria-derived toxins through suppression of intestinal flora. Neomycin has been reported to be as effective as lactulose, and similar efficacy has been reported with vancomycin and metronidazole for the management of HE. However, the adverse effects frequently associated with these antimicrobials limit their use as first-line pharmacological agents. Neomycin is the most commonly used antimicrobial for HE and, although poorly absorbed, systemic exposure to the drug in sufficient amounts causes hearing loss and renal toxicity. Long-term neomycin therapy requires annual auditory testing and continuous monitoring of renal function. Long-term use of metronidazole has been

Synthesis of novel bioactive lactose-derived oligosaccharides by microbial glycoside hydrolases

PubMed Central

Díez-Municio, Marina; Herrero, Miguel; Olano, Agustín; Moreno, F Javier

2014-01-01

Prebiotic oligosaccharides are increasingly demanded within the Food Science domain because of the interesting healthy properties that these compounds may induce to the organism, thanks to their beneficial intestinal microbiota growth promotion ability. In this regard, the development of new efficient, convenient and affordable methods to obtain this class of compounds might expand even further their use as functional ingredients. This review presents an overview on the most recent interesting approaches to synthesize lactose-derived oligosaccharides with potential prebiotic activity paying special focus on the microbial glycoside hydrolases that can be effectively employed to obtain these prebiotic compounds. The most notable advantages of using lactose-derived carbohydrates such as lactosucrose, galactooligosaccharides from lactulose, lactulosucrose and 2-α-glucosyl-lactose are also described and commented. PMID:24690139

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org; Deodhar, Ajita; Thornton, Raymond H.

Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rathermore » than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.« less

Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

PubMed

Jiang, D-L; Yang, J; Jiang, S-Y; Yuan, F-L; Gu, Y-L; Li, J-P; Pei, Z-J

2016-06-24

We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: A prospective study.

PubMed

Vogt, Anika; Reuken, Philipp A; Stengel, Sven; Stallmach, Andreas; Bruns, Tony

2016-03-21

To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis. IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test. Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio > 0.07) compared to 4 (25%) healthy controls (P < 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival. Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study.

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

PubMed

El Oufir, L; Flourié, B; Bruley des Varannes, S; Barry, J L; Cloarec, D; Bornet, F; Galmiche, J P

1996-06-01

To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

PubMed Central

El Oufir, L; Flourié, B; Bruley des Varannes, S; Barry, J L; Cloarec, D; Bornet, F; Galmiche, J P

1996-01-01

BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2

Fish odor syndrome.

PubMed

Rehman, H U

1999-08-01

Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odorless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora.

Intestinal permeability and nutritional status in developmental disorders.

PubMed

Souza, Nilian Carla Silva; Mendonca, Jacqueline Nakau; Portari, Guilherme Vannucchi; Jordao Junior, Alceu Afonso; Marchini, Julio Sergio; Chiarello, Paula Garcia

2012-01-01

Autism is a developmental disorder with a possible connection between dietary components and triggering or worsening of symptoms. An altered intestinal permeability might allow absorption of incompletely digested peptides (gluten and casein) that could produce opioid-like activity on the brain, causing significant changes in behavior. To assess the intestinal permeability and nutritional status of participants with developmental disorders to determine if changes in the intestinal mucosal barrier and/or injury to the intercellular junctions have occurred that might justify application of further dietary modifications. To assess intestinal permeability, the research team analyzed participants urine under fasting conditions, using gas chromatography to determine chromatographic peaks. To assess nutritional status, the team determined participants heights and weights and performed a bioelectric bioimpedance examination at least 4 hours after their most recent meal. In addition, the team determined food intake using three diet diaries. They asked participants and caregivers to register each food consumed during 2 nonconsecutive weekdays and 1 weekend day. The study occurred at the Ribeirao Preto School of Medicine, Sao Paulo University. Seven participants aged 9 to 23 years with developmental disorders (the developmental group, DG) completed the study. The research team recruited them through the Association of Friends of the Autistic Persons of Ribeirao Preto in Ribeirao Preto, Brazil. The control group (CG) consisted of nonsmoking healthy volunteers in the general population who were similar in age to the experimental group and did not suffer from diseases that potentially could influence nutritional status and intestinal function. To assess intestinal permeability, participants ingested 150 mL of an isosmolar solution of the sugars mannitol (2 g) and lactulose (7.5 g) under fasting conditions and the researchers collected all voided urine over a period of 5 hours

A model of blood-ammonia homeostasis based on a quantitative analysis of nitrogen metabolism in the multiple organs involved in the production, catabolism, and excretion of ammonia in humans.

PubMed

Levitt, David G; Levitt, Michael D

2018-01-01

from damaged hepatocytes. Although muscle-NH 3 uptake is normally negligible, it can become important in severe hyperammonemia. The NH 3 -lowering actions of intestinal antibiotics (rifaximin) and lactulose are discussed in detail, with particular emphasis on the seeming lack of importance of the frequently emphasized acidifying action of lactulose in the colon.

Lactulose breath test gas production in childhood IBS is associated with intestinal transit and bowel movement frequency

USDA-ARS?s Scientific Manuscript database

In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. Children (ages 7-1...

Metronidazole-induced encephalopathy in a patient with liver cirrhosis.

PubMed

Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul; Cho, Eun-Young

2011-06-01

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

[Recommendations on therapy for chronic constipation--working group for functional diagnosis and psychosomatics of the austrian society of gastroenterology and hepatology].

PubMed

Vogelsang, H; Pfeiffer, J; Moser, G

2011-02-01

Constipation is one of the most frequent gastroenterological problems, especially among elderly people. Chronic constipation is now defined by the new Rome III criteria. Life style counselling is usually only effective in early stages of disease and for mild types. In patients with constipation one should actively screen for possible causative, medically adverse events. Recently new effective opioid antagonists were introduced to act against constipation in patients on long-term opioid therapy. If these actions fail, medical therapy with polyethylene glycol or lactulose should be favoured in the long-term treatment. Psychodiagnostic queries concerning fear should be included in the diagnostic procedures. Biofeedback is an effective therapy in these cases and especially with pelvic floor dyssynergia. Surgical interventions are rarely indicated or successful with the exception of chronic outlet obstruction with severe anatomic changes. © Georg Thieme Verlag KG Stuttgart · New York.

Unexpected side effect in mCRC: A care-compliant case report of regorafenib-induced hyperammonemic encephalopathy.

PubMed

Quirino, Michela; Rossi, Sabrina; Schinzari, Giovanni; Basso, Michele; Strippoli, Antonia; Cassano, Alessandra; Barone, Carlo

2017-04-01

Regorafenib represents a treatment option in heavily pretreated patients affected by metastatic colorectal cancer (mCRC). Its safety profile is typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse events are manageable. A 56 years-old Caucasian man affected by mCRC with normal hepatic reserve was treated with regorafenib as second-line treatment. After only 2 days of therapy, the patient presented to the emergency department due to impairment of both spatial and temporal orientation and motor function with bradylalia. Serum ammonia level was 191 mmol/L, liver function tests and complete blood count were normal. Regorafenib was withheld and branched chain amino acids and lactulose were administered. Serum ammonia level returned within the normal range, but when regorafenib was restarted at a lower dose level, a new episode of acute confusion arised. Discontinuation of regorafenib after confirmation of hyperammonemia is strongly recommended; reintroduction of the therapy at lower doses after resolution of symptoms related to hyperammonemic encephalopathy has to be discouraged.

Mechanisms of Prebiotic Impact on Health

NASA Astrophysics Data System (ADS)

Steed, H.; Macfarlane, S.

Prebiotics were originally defined as non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activities of one or a limited number of bacteria in the colon, thereby improving host health (Gibson and Roberfroid, 1995). However, a more recent definition is that “A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microbiota that confers benefits upon host wellbeing and health” (Gibson et al., 2004). The principal concept associated with both of these definitions is that the prebiotic has a selective effect on the microbiota that results in an improvement in the health of the host. Common prebiotics in use include inulins, fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), soya-oligosaccharides, xylo-oligosaccharides, pyrodextrins, isomalto-oligosaccharides and lactulose. The majority of studies carried out to date have focused on inulin, FOS and GOS (Macfarlane et al., 2008).

Dielectric properties of glassy disaccharides for electromagnetic interference shielding application

NASA Astrophysics Data System (ADS)

Wlodarczyk, P.; Hawelek, L.; Paluch, M.; Wlodarczyk, A.; Wojnarowska, Z.; Kolano-Burian, A.

2015-11-01

Three amorphous disaccharides (sucrose, trehalose, and lactulose) and their mixtures were studied in order to evaluate their ability to absorb a high frequency (>1 MHz) electromagnetic wave. The materials were characterized by a dielectric loss tangent. It was found out that the highest tan(δ) value is observed in pure amorphous sucrose (tan(δ) = 0.17 at f = 1 MHz at T = 293 K). Moreover, the best Tg/tan(δ) ratio is observed in binary mixtures of sucrose and trehalose. A high glass transition temperature is advantageous as it increases operational temperatures of the material. The high tangent delta in microwave frequencies of sugars is connected with the mobility of sugar groups (possibly -CH2OH). The energy of the electromagnetic wave is converted into rotational movements of side groups and in consequence it is dissipated in the form of heat. It was proven that the polar low molecular glasses such as sugars may form dielectric components of composite microwave absorbers.

Laxative use and clinical correlates in hospitalized patients with obsessive-compulsive disorder: a retrospective descriptive study.

PubMed

Lai, Jianbo; Zhou, Weihua; Lu, Qiaoqiao; Huang, Tingting; Xu, Yi; Hu, Shaohua

2018-01-01

Constipation is a common clinical problem with insufficient attention. Medication-emergent constipation is a rarely studied adverse reaction in patients with obsessive-compulsive disorder (OCD). In this descriptive study, we retrospectively investigated the prevalence of laxative use and its relationship with clinical characteristics in hospitalized OCD patients. A total of 51 OCD patients were included in the final analysis. The proportion of patients using laxatives was 31.4%, and the commonly used laxatives were phenolphthalein tablet, lactulose and congrongtongbian oral liquid (a patent herbal medicine). In the laxative group, hospital stays were longer when compared to the nonlaxative group. Moreover, the dose of paroxetine was higher in patients treated with laxatives than in those without laxative use. Correlation analysis indicated that laxative use was positively associated with hospital stays, as well as the dose of paroxetine. The current study provided a preliminary picture of constipation and laxative use in hospitalized OCD patients. Close monitoring and treatment of constipation are recommended in OCD patients with pharmacotherapy.

Hepatic encephalopathy

PubMed Central

2017-01-01

Abstract Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function occurring in patients with advanced liver diseases. The precise pathophysiology of HE is still under discussion; the leading hypothesis focus on the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. HE produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Minimal HE is diagnosed by abnormal psychometric tests. Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis. HE is classified according to the underlying disease, the severity of manifestations, its time course and the existence of precipitating factors. Treatment of overt HE includes supportive therapies, treatment of precipitating factors, lactulose and/or rifaximin. Routine treatment for minimal HE is only recommended for selected patients. PMID:28533911

Fructans of Jerusalem artichokes: intestinal transport, absorption, fermentation, and influence on blood glucose, insulin, and C-peptide responses in healthy subjects.

PubMed

Rumessen, J J; Bodé, S; Hamberg, O; Gudmand-Høyer, E

1990-10-01

Fructans are naturally occurring plant oligosaccharides with sweetening properties. Fructans (FAs) isolated from Jerusalem artichokes (Helianthus tuberosus) were studied with respect to intestinal handling and influence on blood glucose (BG), insulin, and C-peptide responses in eight healthy subjects. The responses were compared with those for fructose ingestion. The effect of FAs added to a wheat-starch meal was also studied. Standardized breath-hydrogen excretion indicated that FAs were completely malabsorbed and, after a 20-g dose, traces of FA were detected in 24-h urine collections in one subject only. Orocecal transit times were longer for FAs than for lactulose and fructose. The BG and insulin increments were very low after FA ingestion, lower than after fructose ingestion, whereas hydrogen production was much higher. Areas under BG curves tended to be smaller when 10 g FA was added to a 50-g wheat-starch meal, but there was no apparent interference with starch absorption.

Galacto-oligosaccharides and Colorectal Cancer: Feeding our Intestinal Probiome

PubMed Central

Bruno-Barcena, Jose M.; Azcarate-Peril, M. Andrea

2014-01-01

Prebiotics are ingredients selectively fermented by the intestinal microbiota that promote changes in the microbial community structure and/or their metabolism, conferring health benefits to the host. Studies show that β (1–4) galacto-oligosaccharides [β (1–4) GOS], lactulose and fructo-oligosaccharides increase intestinal concentration of lactate and short chain fatty acids, and stool frequency and weight, and they decrease fecal concentration of secondary bile acids, fecal pH, and nitroreductase and β-glucuronidase activities suggesting a clear role in colorectal cancer (CRC) prevention. This review summarizes research on prebiotics bioassimilation, specifically β (1–4) GOS, and their potential role in CRC. We also evaluate research that show that the impact of prebiotics on host physiology can be direct or through modulation of the gut intestinal microbiome, specifically the probiome (autochtonous beneficial bacteria), we present studies on a potential role in CRC progression to finally describe the current state of β (1–4) GOS generation for industrial production. PMID:25584074

Hydrogen breath test in schoolchildren.

PubMed Central

Douwes, A C; Schaap, C; van der Klei-van Moorsel, J M

1985-01-01

The frequency of negative hydrogen breath tests due to colonic bacterial flora which are unable to produce hydrogen was determined after oral lactulose challenge in 98 healthy Dutch schoolchildren. There was a negative result in 9.2%. The probability of a false normal lactose breath test (1:77) was calculated from these results together with those from a separate group of children with lactose malabsorption (also determined by hydrogen breath test). A study of siblings and mothers of subjects with a negative breath test did not show familial clustering of this condition. Faecal incubation tests with various sugars showed an increase in breath hydrogen greater than 100 parts per million in those with a positive breath test while subjects with a negative breath test also had a negative faecal incubation test. The frequency of a false negative hydrogen breath test was higher than previously reported, but this does not affect the superiority of this method of testing over the conventional blood glucose determination. PMID:4004310

Short communication: Promotion of glucagon-like peptide-2 secretion in dairy calves with a bioactive extract from Olea europaea.

PubMed

Morrison, S Y; Pastor, J J; Quintela, J C; Holst, J J; Hartmann, B; Drackley, J K; Ipharraguerre, I R

2017-03-01

Diarrhea episodes in dairy calves involve profound alterations in the mechanism controlling gut barrier function that ultimately compromise intestinal permeability to macromolecules, including pathogenic bacteria. Intestinal dysfunction models suggest that a key element of intestinal adaptation during the neonatal phase is the nutrient-induced secretion of glucagon-like peptide (GLP)-2 and associated effects on mucosal cell proliferation, barrier function, and inflammatory response. Bioactive molecules found in Olea europaea have been shown to induce the release of regulatory peptides from model enteroendocrine cells. The ability to enhance GLP-2 secretion via the feeding of putative GLP-2 secretagogues is untested in newborn calves. The objectives of this study were to determine whether feeding a bioactive extract from Olea europaea (OBE) mixed in the milk replacer (1) can stimulate GLP-2 secretion beyond the response elicited by enteral nutrients and, thereby, (2) improve intestinal permeability and animal growth as well as (3) reduce the incidence of diarrhea in preweaning dairy calves. Holstein heifer calves (n = 60) were purchased, transported to the research facility, and blocked by body weight and total serum protein and assigned to 1 of 3 treatments. Treatments were control (CON), standard milk replacer (MR) and ad libitum starter; CON plus OBE added into MR at 30 mg/kg of body weight (OBE30); and CON plus OBE added into MR at 60 mg/kg of body weight (OBE60). The concentration of GLP-2 was measured at the end of wk 2. Intestinal permeability was measured at the onset of the study and the end of wk 2 and 6, with lactulose and d-mannitol as markers. Treatments did not affect calf growth and starter intake. Compared with CON, administration of OBE60 increased the nutrient-induced response in GLP-2 by about 1 fold and reduced MR intake during the second week of study. Throughout the study, however, all calves had compromised intestinal permeability and a high

Clostridial constipation's broad pathology.

PubMed

Johnson, S

2001-04-01

Clostridia are normally found in the healthy colon, where their numbers are kept in check by other bacteria. However, when they establish themselves in the ileum they become formidable foes. They produce medium-length fatty acids that increase water absorption, causing hypertension and drying up the feces, causing constipation.Furthermore, they can deconjugate bile (impaired fat absorption), metabolyze tryptophan (the most scarce of the essential amino acids), digest fiber (so that the more fiber the patient takes, the more the constipation is exacerbated), digest lecithin, produce carcinogenic metabolites and copious amounts of extremely foul smelling gas, etc. They can also prevent vitamin B12 absorption in the ileum, causing anemia. The synthetic sugar lactulose, which can only be digested by lactobacilli, can help displace the clostridia and resolve the constipation by causing the lactobacilli to produce short fatty acids that have the opposite effect to that of the medium fatty acids produced by clostridia and their accomplices: they cause water retention in the intestines. Copyright 2001 Harcourt Publishers Ltd.

Oatmeal porridge: impact on microflora-associated characteristics in healthy subjects.

PubMed

Valeur, Jørgen; Puaschitz, Nathalie G; Midtvedt, Tore; Berstad, Arnold

2016-01-14

Oatmeal porridge has been consumed for centuries and has several health benefits. We aimed to investigate the effect of oatmeal porridge on gut microflora functions. A total of ten healthy subjects ingested 60 g oatmeal porridge daily for 1 week. The following microflora-associated characteristics were assessed before and after the intervention: intestinal gas production following lactulose ingestion, faecal excretion of SCFA and faecal levels of urease and β-galactosidase. In addition, rectal levels of PGE2 were measured. Microbial fermentation as evaluated by intestinal gas production and excretion of SCFA did not change significantly following the dietary intervention. However, faecal levels of β-galactosidase and urease decreased after eating oatmeal porridge (P=0·049 and 0·031, respectively). Host inflammatory state, as measured by rectal levels of PGE2, also decreased, but the change was not significant (P=0·168). The results suggest that oatmeal porridge has an effect on gut microbial functions and may possess potential prebiotic properties that deserve to be investigated further.

Bacterial overgrowth and methane production in children with encopresis.

PubMed

Leiby, Alycia; Mehta, Devendra; Gopalareddy, Vani; Jackson-Walker, Susan; Horvath, Karoly

2010-05-01

To assess the prevalence of small intestinal bacterial overgrowth (SIBO) and methane production in children with encopresis. Radiographic fecal impaction (FI) scores were assessed in children with secondary, retentive encopresis and compared with the breath test results. Breath tests with hypoosmotic lactulose solution were performed in both the study patients (n = 50) and gastrointestinal control subjects (n = 39) groups. The FI scores were significantly higher in the patients with encopresis who were methane producers (P < .01). SIBO was diagnosed in 21 of 50 (42%) patients with encopresis and 9 of 39 (23%) of control subjects (P = .06). Methane was produced in 56% of the patients with encopresis versus 23.1% of the control subjects in the gastrointestinal group (P < .01). Fasting methane level was elevated in 48% versus 10.3 %, respectively (P < .01). Children with FI and encopresis had a higher prevalence of SIBO, elevated basal methane levels, and higher methane production. Methane production was associated with more severe colonic impaction. Further study is needed to determine whether methane production is a primary or secondary factor in the pathogenesis of SIBO and encopresis.

Hepatic encephalopathy: cause and possible management with botanicals.

PubMed

Tripathi, Suyash; Tripathi, Yamini B

2014-01-01

Hepatic encephalopathy is a brain functional disorder, characterized by neuropsychiatric abnormalities with liver failure. High blood ammonia, causing glutamate neurotoxicity is the basic cause, finally leading to low-grade cerebral edema. Its manifestation is more likely in patients of sepsis, oxidative stress, generalized inflammation, gut mal-functioning, amoebiaesis, viral hepatitis, nervous imbalance, etc. Thus, the therapeutic goals primarily include the maintenance of proper blood supply and prevention of hypoxic condition in liver, along with management of factors responsible for high blood ammonia, oxidative stress, inflammation, and high GI- serotonin. The drugs in clinical practice include lactulose, sodium benzoate, flumazenil and rifaximin, supplementation of zinc, branched chain amino acids (BCAA), l-ornithine-l aspartate, antioxidants and iNOS inhibitors. However, herbal formulations would be of great importance as it shows multi-targeted action because it possesses a natural cocktail of secondary metabolites. It can collectively act as an antioxidant, anti-inflammatory, prebiotic, hepatoprotective and neuron-protective agents. We have briefly outlined some of these plants and also recent patents useful in the management of hepatic encephalopathy.

Household Environmental Conditions Are Associated with Enteropathy and Impaired Growth in Rural Bangladesh

PubMed Central

Lin, Audrie; Arnold, Benjamin F.; Afreen, Sadia; Goto, Rie; Huda, Tarique Mohammad Nurul; Haque, Rashidul; Raqib, Rubhana; Unicomb, Leanne; Ahmed, Tahmeed; Colford, John M.; Luby, Stephen P.

2013-01-01

We assessed the relationship of fecal environmental contamination and environmental enteropathy. We compared markers of environmental enteropathy, parasite burden, and growth in 119 Bangladeshi children (≤ 48 months of age) across rural Bangladesh living in different levels of household environmental cleanliness defined by objective indicators of water quality and sanitary and hand-washing infrastructure. Adjusted for potential confounding characteristics, children from clean households had 0.54 SDs (95% confidence interval [CI] = 0.06, 1.01) higher height-for-age z scores (HAZs), 0.32 SDs (95% CI = −0.72, 0.08) lower lactulose:mannitol (L:M) ratios in urine, and 0.24 SDs (95% CI = −0.63, 0.16) lower immunoglobulin G endotoxin core antibody (IgG EndoCAb) titers than children from contaminated households. After adjusting for age and sex, a 1-unit increase in the ln L:M was associated with a 0.33 SDs decrease in HAZ (95% CI = −0.62, −0.05). These results are consistent with the hypothesis that environmental contamination causes growth faltering mediated through environmental enteropathy. PMID:23629931

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-02-25

trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. Based on the combined Cochrane Hepato-Biliary Group score, we classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2017-05-18

BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-09-17

), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on

[Analysis of breath hydrogen (H2) in diagnosis of gastrointestinal function: validation of a pocket breath H2 test analyzer].

PubMed

Braden, B; Braden, C P; Klutz, M; Lembcke, B

1993-04-01

Breath hydrogen (H2) analysis, as used in gastroenterologic function tests, requires a stationary analysis system equipped with a gaschromatograph or an electrochemical sensor cell. Now a portable breath H2-analyzer has been miniaturized to pocket size (104 mm x 62 mm x 29 mm). The application of this device in clinical practice has been assessed in comparison to the standard GMI-exhaled monitor. The pocket analyzer showed a linear response to standards with H2-concentrations ranging from 0-100 ppm (n = 7), which was not different from the GMI-apparatus. The correlation of both methods during clinical application (lactose tolerance tests, mouth-to-coecum transit time determined with lactulose) was excellent (Y = 1.08 X + 0.96; r = 0.959). Using the new device, both, analysis (3 s vs. 90 s) and the reset-time (43 s vs. 140 s) were shorter whereas calibration was more feasible with the GMI-apparatus. It is concluded, that the considerably cheaper pocket-sized breath H2-analyzer is as precise and sensitive as the GMI-exhaled monitor, and thus presents a valid alternative for H2-breath tests.

Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis.

PubMed

Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

2015-11-07

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

Isolation, biochemical characterization and antibiofilm effect of a lectin from the marine sponge Aplysina lactuca.

PubMed

Carneiro, Rômulo Farias; Lima, Paulo Henrique Pinheiro de; Chaves, Renata Pinheiro; Pereira, Rafael; Pereira, Anna Luísa; de Vasconcelos, Mayron Alves; Pinheiro, Ulisses; Teixeira, Edson Holanda; Nagano, Celso Shiniti; Sampaio, Alexandre Holanda

2017-06-01

A new lectin was isolated from the marine sponge Aplysina lactuca (ALL) by combining ammonium sulfate precipitation and affinity chromatography on guar gum matrix. ALL showed affinity for the disaccharides α-lactose, β-lactose and lactulose (Ka=12.5, 31.9 and 145.5M -1 , respectively), as well as the glycoprotein porcine stomach mucin. Its hemagglutinating activity was stable in neutral acid pH values and temperatures below 60°C. ALL is a dimeric protein formed by two covalently linked polypeptide chains. The average molecular mass, as determined by Electrospray Ionization Mass Spectrometry (ESI-MS), was 31,810±2Da. ESI-MS data also indicated the presence of three cysteines involved in one intrachain and one interchain disulfide bond. The partial amino acid sequence of ALL was determined by tandem mass spectrometry. Eight tryptic peptides presented similarity with lectin I isolated from Axinella polypoides. Its secondary structure is predominantly β-sheet, as indicated by circular dichroism (CD) spectroscopy. ALL agglutinated gram-positive and gram-negative bacterial cells, and it were able to significantly reduce the biomass of the bacterial biofilm tested at dose- dependent effect. Copyright © 2017 Elsevier B.V. All rights reserved.

New Trends for the Evaluation of Heat Treatments of Milk

PubMed Central

Di Costanzo, Maria Gabriella; Mattera, Maria

2017-01-01

Milk is generally very rich in nutrients and this may lead it to be an ideal growth environment for many microorganisms, including pathogens, so effective measurements aiming to ensure total microbiological safety of milk and minimize the risk to human health are needed. Milk heat treatments are the most common practices carried out to inhibit the microbial growth; therefore it is necessary to have analytical procedures that are more and more up-to-date and capable of detecting the effectiveness of the heat treatments. Most of the reference and official methods to assess heat treatment in milk are based on the evaluation of the modifications of some milk components following the thermal process, such as the determination of enzyme activities (alkaline phosphatase and lactoperoxidase), whey proteins, Maillard reaction compounds (generally furosine), and lactulose. Besides the most common techniques (liquid and gas chromatography, capillary electrophoresis, or spectroscopy) used for the detection of single thermal indicators, new approaches, such as chemometric studies or more recent techniques, including size-exclusion chromatography with online electrospray mass spectrometry or stable isotope ratio mass spectrometry, are discussed in this review in order to evaluate heat treatment in milk. PMID:29230345

A prospective randomised trial of probiotics in critically ill patients.

PubMed

McNaught, Clare E; Woodcock, Nicholas P; Anderson, Alexander D G; MacFie, John

2005-04-01

Probiotics exert a beneficial effect on the host through modulation of gastrointestinal microflora. The aim of this study was to investigate the effect of the probiotic Lactobacillus plantarum 299v on gut barrier function and the systemic inflammatory response in critically ill patients. One hundred and three critically ill patients were randomised to receive an oral preparation containing L. plantarum 299v (ProViva) in addition to conventional therapy (treatment group, n = 52) or conventional therapy alone (control group, n = 51). Serial outcome measures included gastric colonisation, intestinal permeability (lactulose/rhamnose dual-sugar probe technique), endotoxin exposure (IgM EndoCAb), C-reactive protein and Interleukin 6 levels. L. plantarum had no identifiable effect on gastric colonisation, intestinal permeability, endotoxin exposure or serum CRP levels. There were no differences between the groups in terms of septic morbidity or mortality. On day 15 serum IL-6 levels were significantly lower in the treatment group compared to controls. The enteral administration of L. plantarum 299v to critically ill patients was associated with a late attenuation of the systemic inflammatory response. This was not accompanied by any significant changes in the intestinal microflora, intestinal permeability, endotoxin exposure, septic morbidity or mortality.

The Pharmabiotic Approach to Treat Hyperammonemia

PubMed Central

Liu, Jing; Lkhagva, Enkhchimeg; Chung, Hea-Jong; Kim, Hyeon-Jin; Hong, Seong-Tshool

2018-01-01

Ammonia is constantly produced as a metabolic waste from amino acid catabolism in mammals. Ammonia, the toxic waste metabolite, is resolved in the liver where the urea cycle converts free ammonia to urea. Liver malfunctions cause hyperammonemia that leads to central nervous system (CNS) dysfunctions, such as brain edema, convulsions, and coma. The current treatments for hyperammonemia, such as antibiotics or lactulose, are designed to decrease the intestinal production of ammonia and/or its absorption into the body and are not effective, besides being often accompanied by side effects. In recent years, increasing evidence has shown that modifications of the gut microbiota could be used to treat hyperammonemia. Considering the role of the gut microbiota and the physiological characteristics of the intestine, the removal of ammonia from the intestine by modulating the gut microbiota would be an ideal approach to treat hyperammonemia. In this review, we discuss the significance of hyperammonemia and its related diseases and the efficacy of the current management methods for hyperammonemia to understand the mechanism of ammonia transport in the human body. The possibility to use the gut microbiota as pharmabiotics to treat hyperammonemia and its related diseases is also explored. PMID:29382084

Multi-antioxidant supplementation does not prevent an increase in gut permeability after lower torso ischemia and reperfusion in humans.

PubMed

Wijnen, M H W A; Vader, H L; Roumen, R M H

2002-01-01

An increase in gut permeability can have serious consequences leading to sepsis and multiple organ failure. After lower torso ischemia an increase in gut permeability is seen in both animals and humans. There is proof that this can be modified by antioxidant supplementation. In this prospective, randomized study we have looked at the influence of a multiantioxidant supplementation regime, using allopurinol, vitamins E and C, mannitol and N-acetylcysteine, perioperatively. Twenty-two patients received standard treatment and 20 patients received supplementation. Gut permeability was determined using a double sugar test with lactulose and rhamnose. A significant increase in gut permeability was found neither in the non-treatment group (p = 0.012) nor in the treatment group (p = 0.006) after 6 and 24 h. No difference was found between the group receiving antioxidants and the standard treatment group. p = 0.93 6 h post clamp; p = 0.97 24 h post clamp. In this study we have not found an influence of multiantioxidant supplementation on gut permeability after lower torso ischemia. Possible explanations for this negative result are being discussed. Copyright 2002 S. Karger AG, Basel

Pharmacotherapy of hepatic encephalopathy in cirrhosis.

PubMed

Romero-Gómez, Manuel

2010-06-01

Hepatic encephalopathy (HE) is a major complication encountered in nearly half of the patients with liver cirrhosis. A review of the safety and efficacy of current therapies for HE that seek to pre-empt ammonia production and/or to increase its elimination, reducing inflammation, blocking benzodiazepine-like compound production, and supporting systemic hemodynamics. Insight into some recent advances in the management of HE that could modify our therapeutic approach to end-stage liver disease. Cirrhotic individuals during an overt HE episode require careful management, focusing on precipitant factors as well as metabolic and hemodynamic derangements. Intestinal ammoniagenesis requires flora modification by antibiotics, prebiotics and probiotics; glutaminase inhibition as well as antibiotics to pre-empt systemic inflammation. Hemodynamic/fluid support is essential. Nutritional support is crucial and hypoproteinemic diets should be avoided. Blocking benzodiazepine-like compounds by the use of flumazenil could be useful in patients with severe, benzodiazepine-induced HE. Long-term rifaximin is well tolerated, does not promote resistance and could decrease overt HE bouts in patients with previous episodes of overt HE. Lactulose is better than no treatment in improving quality of life in patients with minimal HE; it also acts as secondary prophylaxis following overt HE.

Rhubarb Monomers Protect Intestinal Mucosal Barrier in Sepsis via Junction Proteins

PubMed Central

Wang, Lyu; Cui, Yun-Liang; Zhang, Zhe; Lin, Zhao-Fen; Chen, De-Chang

2017-01-01

Background: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. Methods: Healthy male Sprague-Dawley rats (weighing 230–250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured. Results: Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001), and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P < 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P < 0.001), D (0.029 ± 0.003, P < 0.001), E (0.026 ± 0.003, P < 0.001), F (0.027 ± 0.003, P < 0.001), G (0.030 ± 0.005, P < 0.001), and H (0.026 ± 0

The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial.

PubMed

Zhou, Ye-Ping; Jiang, Zhu-Ming; Sun, Yong-Hua; Wang, Xiu-Rong; Ma, En-Ling; Wilmore, Douglas

2003-01-01

This research was conducted to evaluate the effect of enterally administered glutamine (gln) dipeptide on metabolic, gastrointestinal, and outcome parameters after severe burn injury. Forty thermally injured patients with total body surface burns ranging between 50% and 80%, and third-degree burns ranging between 20% and 40% and without respiratory injuries, were randomized into a prospective, double-blind, controlled clinical trial. One group received gln-enriched enteral nutrition and the other group received the standard enteral formulation. Tube feedings were initiated on postburn day 1 (PBD +1), and isocaloric and isonitrogenous feedings were administered to both groups until PBD +12. The gln was given as the dipeptide of alanyl-gln (Ajinomoto, Tokyo, Japan), which provided 0.35 g gln/kg body weight/d. Plasma amino acid profiles, serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (which reflects gut permeability) were measured at specific times throughout the clinical course. Wound healing at day 30 was assessed, and length of hospital stay and total costs were determined at discharge. The 2 groups were similar in terms of age and extent of injury. Plasma gln concentrations were approximately 300 umol/L in both groups on PBD +1 and remained low in the control group (399 +/- 40 umol/L, mean +/- SD) but increased toward normal in the supplemented group to 591 +/- 74 (p = .048). Lactulose/mannitol ratios were increased above normal on POD +1 (control, 0.221 +/- 0.169; gln, 0.268 +/- 0.202; not significant), reflecting increased intestinal permeability after burn injury. On POD +3, the ratio in the gln group was lower than control (0.025 +/- 0.008 versus 0.049 +/- 0.016; p = .0001), and both groups returned toward normal ratios with time. Endotoxin levels on PBD +1 were elevated in both groups (control, 0.089 +/- 0.023 EU/mL; gln, 0.103 +/- 0.037 EU/mL; NS) but decreased significantly on PBD +3 in the patients receiving gln. Hospital stay

Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice.

PubMed

Justino, Priscilla F C; Melo, Luis F M; Nogueira, Andre F; Costa, Jose V G; Silva, Luara M N; Santos, Cecila M; Mendes, Walber O; Costa, Marina R; Franco, Alvaro X; Lima, Aldo A; Ribeiro, Ronaldo A; Souza, Marcellus H L P; Soares, Pedro M G

2014-05-01

Intestinal mucositis is an important toxic side effect of 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii is known to protect from intestinal injury via an effect on the gastrointestinal microbiota. The objective of the present study was to evaluate the effect of S. boulardii on intestinal mucositis induced by 5-FU in a murine model. Mice were divided into saline, saline (control)+5-FU or 5-FU+S. boulardii (16 × 10⁹ colony-forming units/kg) treatment groups, and the jejunum and ileum were removed after killing of mice for the evaluation of histopathology, myeloperoxidase (MPO) activity, and non-protein sulfhydryl group (mainly reduced glutathione; GSH), nitrite and cytokine concentrations. To determine gastric emptying, phenol red was administered orally, mice were killed 20 min after administration, and the absorbance of samples collected from the mice was measured by spectrophotometry. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following oral administration. S. boulardii significantly reversed the histopathological changes in intestinal mucositis induced by 5-FU and reduced the inflammatory parameters: neutrophil infiltration (control 1·73 (SEM 0·37) ultrastructural MPO (UMPO)/mg, 5-FU 7·37 (SEM 1·77) UMPO/mg and 5-FU+S. boulardii 4·15 (SEM 0·73) UMPO/mg); nitrite concentration (control 37·00 (SEM 2·39) μm, 5-FU 59·04 (SEM 11·41) μm and 5-FU+S. boulardii 37·90 (SEM 5·78) μm); GSH concentration (control 477·60 (SEM 25·25) μg/mg, 5-FU 270·90 (SEM 38·50) μg/mg and 5-FU+S. boulardii 514·00 (SEM 38·64) μg/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF-α and IL-1β by 48·92 and 32·21 % in the jejunum and 38·92 and 61·79 % in the ileum. In addition, S. boulardii decreased the concentrations of chemokine (C-X-C motif) ligand 1 by 5-fold in the jejunum and 3-fold in the ileum. Interestingly, S. boulardii reduced the delay in gastric emptying

What tests should you use to assess small intestinal bacterial overgrowth in systemic sclerosis?

PubMed

Braun-Moscovici, Yolanda; Braun, Marius; Khanna, Dinesh; Balbir-Gurman, Alexandra; Furst, Daniel E

2015-01-01

Small intestinal bacterial overgrowth (SIBO) plays a major role in the pathogenesis of malabsorption in SSc patients and is a source of great morbidity and even mortality, in those patients. This manuscript reviews which tests are valid and should be used in SSc when evaluating SIBO. We performed systematic literature searches in PubMed, Embase and the Cochrane library from 1966 up to November 2014 for English language, published articles examining bacterial overgrowth in SSc (e.g. malabsorption tests, breath tests, xylose test, etc). Articles obtained from these searches were reviewed for additional references. The validity of the tests was evaluated according to the OMERACT principles of truth, discrimination and feasibility. From a total of 65 titles, 22 articles were reviewed and 20 were ultimately extracted to examine the validity of tests for GI morphology, bacterial overgrowth and malabsorption in SSc. Only 1 test (hydrogen and methane breath tests) is fully validated. Four tests are partially validated, including jejunal cultures, xylose, lactulose tests, and 72 hours fecal fat test. Only 1 of a total of 5 GI tests of bacterial overgrowth (see above) is fully validated in SSc. For clinical trials, fully validated tests are preferred, although some investigators use partially validated tests (4 tests). Further validation of GI tests in SSc is needed.

Prevalence of Small Intestinal Bacterial Overgrowth among Chronic Pancreatitis Patients: A Case-Control Study

PubMed Central

Bouchard, Simon; Sidani, Sacha

2016-01-01

Background. Patients with chronic pancreatitis (CP) exhibit numerous risk factors for the development of small intestinal bacterial overgrowth (SIBO). Objective. To determine the prevalence of SIBO in patients with CP. Methods. Prospective, single-centre case-control study conducted between January and September 2013. Inclusion criteria were age 18 to 75 years and clinical and radiological diagnosis of CP. Exclusion criteria included history of gastric, pancreatic, or intestinal surgery or significant clinical gastroparesis. SIBO was detected using a standard lactulose breath test (LBT). A healthy control group also underwent LBT. Results. Thirty-one patients and 40 controls were included. The patient group was significantly older (53.8 versus 38.7 years; P < 0.01). The proportion of positive LBTs was significantly higher in CP patients (38.7 versus 2.5%: P < 0.01). A trend toward a higher proportion of positive LBTs in women compared with men was observed (66.6 versus 27.3%; P = 0.056). The subgroups with positive and negative LBTs were comparable in demographic and clinical characteristics, use of opiates, pancreatic enzymes replacement therapy (PERT), and severity of symptoms. Conclusion. The prevalence of SIBO detected using LBT was high among patients with CP. There was no association between clinical features and the risk for SIBO. PMID:27446865

Prevalence of Small Intestinal Bacterial Overgrowth among Chronic Pancreatitis Patients: A Case-Control Study.

PubMed

Therrien, Amelie; Bouchard, Simon; Sidani, Sacha; Bouin, Mickael

2016-01-01

Background. Patients with chronic pancreatitis (CP) exhibit numerous risk factors for the development of small intestinal bacterial overgrowth (SIBO). Objective. To determine the prevalence of SIBO in patients with CP. Methods. Prospective, single-centre case-control study conducted between January and September 2013. Inclusion criteria were age 18 to 75 years and clinical and radiological diagnosis of CP. Exclusion criteria included history of gastric, pancreatic, or intestinal surgery or significant clinical gastroparesis. SIBO was detected using a standard lactulose breath test (LBT). A healthy control group also underwent LBT. Results. Thirty-one patients and 40 controls were included. The patient group was significantly older (53.8 versus 38.7 years; P < 0.01). The proportion of positive LBTs was significantly higher in CP patients (38.7 versus 2.5%: P < 0.01). A trend toward a higher proportion of positive LBTs in women compared with men was observed (66.6 versus 27.3%; P = 0.056). The subgroups with positive and negative LBTs were comparable in demographic and clinical characteristics, use of opiates, pancreatic enzymes replacement therapy (PERT), and severity of symptoms. Conclusion. The prevalence of SIBO detected using LBT was high among patients with CP. There was no association between clinical features and the risk for SIBO.

Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting.

PubMed

Tytgat, G N; Heading, R C; Müller-Lissner, S; Kamm, M A; Schölmerich, J; Berstad, A; Fried, M; Chaussade, S; Jewell, D; Briggs, A

2003-08-01

Gastro-oesophageal reflux disease (GERD) and constipation have a major impact on public health; however, the wide variety of treatment options presents difficulties for recommending therapy. Lack of definitive guidelines in pharmacy and general practice medicine further exacerbates the decision dilemma. To address these issues, a panel of experts discussed the principles and practice of treating GERD and constipation in the general population and in pregnancy, with the aim of developing respective treatment guidelines. The panel recommended antacids 'on-demand' as the first-line over-the-counter treatment in reflux, and as rescue medication for immediate relief when reflux breaks through with proton pump inhibitors. Calcium/magnesium-based antacids were recommended as the treatment of choice for pregnant women because of their good safety profile. In constipation, current data do not distinguish a hierarchy between polyethylene glycol (PEG)-based laxatives and other first-line treatments, although limitations are associated with stimulant- and bulk-forming laxatives. Where data are available, PEG is superior to lactulose in terms of efficacy. In pregnancy, PEG-based laxatives meet the criteria for the ideal treatment. The experts developed algorithms that present healthcare professionals with clear treatment options and management strategies for GERD and constipation in pharmacy and general practice medicine.

A Single-Batch Fermentation System to Simulate Human Colonic Microbiota for High-Throughput Evaluation of Prebiotics

PubMed Central

Sasaki, Daisuke; Fukuda, Itsuko; Tanaka, Kosei; Yoshida, Ken-ichi; Kondo, Akihiko; Osawa, Ro

2016-01-01

We devised a single-batch fermentation system to simulate human colonic microbiota from fecal samples, enabling the complex mixture of microorganisms to achieve densities of up to 1011 cells/mL in 24 h. 16S rRNA gene sequence analysis of bacteria grown in the system revealed that representatives of the major phyla, including Bacteroidetes, Firmicutes, and Actinobacteria, as well as overall species diversity, were consistent with those of the original feces. On the earlier stages of fermentation (up to 9 h), trace mixtures of acetate, lactate, and succinate were detectable; on the later stages (after 24 h), larger amounts of acetate accumulated along with some of propionate and butyrate. These patterns were similar to those observed in the original feces. Thus, this system could serve as a simple model to simulate the diversity as well as the metabolism of human colonic microbiota. Supplementation of the system with several prebiotic oligosaccharides (including fructo-, galacto-, isomalto-, and xylo-oligosaccharides; lactulose; and lactosucrose) resulted in an increased population in genus Bifidobacterium, concomitant with significant increases in acetate production. The results suggested that this fermentation system may be useful for in vitro, pre-clinical evaluation of the effects of prebiotics prior to testing in humans. PMID:27483470

Effects of mesocaval shunt on the pharmacokinetics of metronidazole in young rats.

PubMed

Guillé, Beatriz E Perez; Alvarez, Fernando Villegas; Toledo López, Alejandra R; Bravo-Luna, Miguel A Jiménez; Soriano-Rosales, Rosa E; Lares-Asseff, Ismael; Arrellin, Gerardo; Guillé, Maria G Pérez

2005-01-01

Prophylactic and therapeutic management of portosystemic encephalopathies is based on protein restriction in the diet, and the use of lactulose and antibiotics such as metronidazole. These actions intend to reduce the main source of intestinal ammonia production and release into the systemic circulation. The aim of this study was to evaluate the medium-term effects of mesocaval shunt on the pharmacokinetics of metronidazole in rats with healthy livers. Male Lewis rats were divided into two groups. The first group was subjected to mesocaval shunt (MCS) and the other employed as a control. The following tests were carried out in both groups: metronidazole pharmacokinetics, determination of ALT, AST, albumin, urea and ammonium, liver weight and histomorphology. A loss in body and liver weight was registered in rats subjected to MCS. AST levels also increased compared to controls. Significant differences in almost all pharmacokinetic parameters were detected between MCS and control rats, especially in Kel, AUC and Cmax. Modifications in metronidazole pharmacokinetics and liver weight changes without microstructural modification secondary to MCS were found. We suggest that individual drug-monitoring and pharmacokinetic analysis must be carried out in metronidazole medicated patients with modifications in portal circulation with or with out macro or micro liver structural alterations.

Use of macrogol 4000 in chronic constipation.

PubMed

De Giorgio, R; Cestari, R; Corinaldesi, R; Stanghellini, V; Barbara, G; Felicani, C; Di Nardo, G; Cucchiara, S

2011-08-01

Chronic constipation is a common functional disorder of the gastrointestinal tract, affecting up to 35% of the general population, and especially the elderly. However, its definition as perceived by the patient can vary, making it difficult to understand the problem and find appropriate therapeutic measures. The approach to chronic constipation, thus, needs a thorough understanding of the patient's complaint and the main pathophysiological mechanism requiring treatment. Lifestyle changes do not usually meet with complete patient satisfaction. Other treatments include different types of laxatives. Of these, osmotic laxatives appear one of the most effective and are, therefore, frequently prescribed. This review will cover the topic of osmotic laxatives, specifically focusing on polyethylene glycol (PEG/macrogol 4000) in chronic constipation and as a key agent for bowel cleansing prior to colonoscopy. PEG formulations, including macrogol 4000, are safe, effective treatments for constipation, even in children and elderly patients. Macrogol 4000 may well be more palatable than combined formulations (macrogol 3350 with electrolytes), which could help improve adherence to the long-term treatment required for chronic constipation. PEG/macrogol is also recommended as an effective option for bowel cleansing prior to colonoscopy. The improved cost-effectiveness of macrogol over other commonly prescribed laxatives, such as lactulose, should be taken into consideration.

Influence of feeding thermally peroxidized soybean oil on growth performance, digestibility, and gut integrity in finishing pigs.

PubMed

Overholt, Martin F; Dilger, Anna C; Boler, Dustin D; Kerr, Brian J

2018-05-26

Consumption of peroxidized lipids has been shown to reduce pig performance and energy and lipid digestibility. Objectives of the current study were to evaluate the effect of feeding soybean oil (SO) with different levels of peroxidation on growth performance, lipid, N, and GE digestibility, plasma Trp, and gut integrity in finishing pigs. Fifty-six barrows (46.7 ± 5.1 kg initial BW) were randomly assigned to one of four diets in each of two dietary phases, containing either 10% fresh SO (22.5 °C) or thermally processed SO (45 °C for 288 h, 90 °C for 72 h, or 180 °C for 6 h), each infused with of 15 L/min of air. Peroxide values were 2.0, 17.4, 123.6, and 19.4 mEq/kg; 2,4-decadienal values were 2.07, 1.90, 912.15, and 915.49 mg/kg; and 4-hydroxynonenal concentrations were 0.66, 1.49, 170.48, and 82.80 mg/kg, for the 22.5, 45, 90, and 180 °C processed SO, respectively. Pigs were individually housed and fed ad libitum for 81 d to measure growth performance, including a metabolism period to collect urine and feces for determination of GE, lipid, N digestibility, and N retention. Following the last day of fecal and urine collection when pigs were in the metabolism crates, lactulose and mannitol were fed and subsequently measured in the urine to evaluate gut permeability, while markers of oxidative stress were evaluated in plasma, urine, and liver. There were no differences observed in ADFI (P = 0.91), but average daily gain (ADG) and gain:feed G:F were decreased in pigs fed 90 °C SO diet (P ≤ 0.07) compared to pigs fed the other SO diets. Pigs fed the 90 and 180 °C SO had the lowest (P = 0.05) DE as a % of GE compared to pigs fed the 22.5 °C SO, with pigs fed the 45 °C SO being intermediate. Lipid digestibility was similarly affected (P = 0.01) as energy digestibility, but ME as a % of DE was not affected by dietary treatment (P = 0.16). There were no effects of lipid peroxidation on N digested, N retained, or the urinary lactulose:mannitol ratio (P ≥ 0

Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy.

PubMed

Ghoshal, Uday C; Shukla, Ratnakar; Ghoshal, Ujjala

2017-03-15

The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this paradigm shift is the realization that gut dysbiosis, including small intestinal bacterial overgrowth (SIBO), causes IBS symptoms. Between 4% and 78% of patients with IBS and 1% and 40% of controls have SIBO; such wide variations in prevalence might result from population differences, IBS diagnostic criteria, and, most importantly, methods to diagnose SIBO. Although quantitative jejunal aspirate culture is considered the gold standard for the diagnosis of SIBO, noninvasive hydrogen breath tests have been popular. Although the glucose hydrogen breath test is highly specific, its sensitivity is low; in contrast, the early-peak criteria in the lactulose hydrogen breath test are highly nonspecific. Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients. Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut, providing support for the micro-organic basis of IBS. A recent proof-of-concept study showing the high frequency of symptom improvement in patients with IBS with SIBO further supports this hypothesis.

Resection of the large bowel suppresses hunger and food intake and modulates gastrointestinal fermentation.

PubMed

Hettiarachchi, Priyadarshika; Wickremasinghe, A Rajitha; Frost, Gary S; Deen, Kemal I; Pathirana, Ajith A; Murphy, Kevin G; Jayaratne, SriLal D

2016-08-01

To assess appetite and gut hormone levels in patients following partial (PR) or total resection (TR) of the large bowel. A comparative cross sectional study was carried out with healthy controls (n = 99) and patients who had undergone PR (n = 64) or TR (n = 12) of the large bowel. Participants consumed a standard (720 kcal) breakfast meal at 0830 (t = 0) h followed by lactulose (15 g) and a buffet lunch (t = 210 min). Participants rated the subjective feelings of hunger at t = -30, 0, 30, 60, 120, and 180 min. Breath hydrogen (BH) concentrations were also evaluated. In a matched subset (11 controls, 11 PR and 9 TR patients) PYY and GLP-1 concentrations were measured following breakfast. The primary outcome measure was appetite, as measured using visual analogue scales and the buffet lunch. The secondary outcome was BH concentrations following a test meal. PR and TR participants had lower hunger and energy intake at the buffet lunch meal compared to controls. PR subjects had higher BH concentrations compared to controls and TR subjects. BH levels correlated with circulating GLP-1 levels at specific time points. PR or TR of the large bowel reduced feelings of hunger and energy intake, and PR increased gastrointestinal fermentation. © 2016 The Obesity Society.

In vitro colonic fermentation and glycemic response of different kinds of unripe banana flour.

PubMed

Menezes, Elizabete Wenzel; Dan, Milana C T; Cardenette, Giselli H L; Goñi, Isabel; Bello-Pérez, Luis Arturo; Lajolo, Franco M

2010-12-01

This work aimed to study the in vitro colonic fermentation profile of unavailable carbohydrates of two different kinds of unripe banana flour and to evaluate their postprandial glycemic responses. The unripe banana mass (UBM), obtained from the cooked pulp of unripe bananas (Musa acuminata, Nanicão variety), and the unripe banana starch (UBS), obtained from isolated starch of unripe banana, plantain type (Musa paradisiaca) in natura, were studied. The fermentability of the flours was evaluated by different parameters, using rat inoculum, as well as the glycemic response produced after the ingestion by healthy volunteers. The flours presented high concentration of unavailable carbohydrates, which varied in the content of resistant starch, dietary fiber and indigestible fraction (IF). The in vitro colonic fermentation of the flours was high, 98% for the UBS and 75% for the UBM when expressed by the total amount of SCFA such as acetate, butyrate and propionate in relation to lactulose. The increase in the area under the glycemic curve after ingestion of the flours was 90% lower for the UBS and 40% lower for the UBM than the increase produced after bread intake. These characteristics highlight the potential of UBM and UBS as functional ingredients. However, in vivo studies are necessary in order to evaluate the possible benefit effects of the fermentation on intestinal health.

Constipation in adults.

PubMed

Mueller-Lissner, Stefan A; Wald, Arnold

2010-07-05

Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid, and depend in part on the perception of normal bowel habit. Constipation is highly prevalent, with approximately 12 million general practitioner prescriptions for laxatives in England in 2001. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug interventions, bulk-forming laxatives, faecal softeners, stimulant laxatives, osmotic laxatives, prostaglandin derivatives, and 5-HT4 agonists in adults with idiopathic chronic constipation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 51systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: arachis oil, biofeedback, bisacodyl, cascara, docusate, exercise, glycerol/glycerine suppositories, high-fibre diet, increasing fluids, ispaghula husk, lactitol, lactulose, lubiprostone, macrogols (polyethylene glycols), magnesium salts, methylcellulose, paraffin, phosphate enemas, seed oils, senna, sodium citrate enemas, prucalopride, and sterculia.

Constipation in adults.

PubMed

Frizelle, Frank; Barclay, Murray

2007-08-01

Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid, and in part depend on the perception of normal bowel habit. Constipation is highly prevalent, with approximately 12 million general practitioner prescriptions for laxatives in England in 2001. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug interventions, and of other interventions, in adults with idiopathic chronic constipation? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2006 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 42 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: arachis oil, biofeedback, bisacodyl, cascara, docusate, exercise, glycerine suppositories, glycerol, high-fibre diet, increasing fluids, ispaghula husk, lactitol, lactulose, macrogols (polyethylene glycols), magnesium salts, methylcellulose, paraffin, phosphate enemas, seed oils, senna, sodium citrate enemas, sterculia.

Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms.

PubMed

Di Stefano, M; Strocchi, A; Malservisi, S; Veneto, G; Ferrieri, A; Corazza, G R

2000-08-01

Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas-related symptoms with conflicting results. To study the relationship between gaseous symptoms and colonic gas production and to test the efficacy of rifaximin, a new non-absorbable antimicrobial agent, on these symptoms. Intestinal gas production was measured by hydrogen (H2) and methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34 functional patients. Only the 34 functional patients took part in a double-blind, double-dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7 days), or activated charcoal (400 mg b.d per 7 days). The following parameters were evaluated at the start of the study and 1 and 10 days after therapy: bloating, abdominal pain, number of flatus episodes, abdominal girth, and cumulative breath H2 excretion. Hydrogen excretion was greater in functional patients than in healthy volunteers. Rifaximin, but not activated charcoal, led to a significant reduction in H2 excretion and overall severity of symptoms. In particular, in patients treated with rifaximin, a significant reduction in the mean number of flatus episodes and of mean abdominal girth was evident. In patients with gas-related symptoms the colonic production of H2 is increased. Rifaximin significantly reduces this production and the excessive number of flatus episodes.

Fiber and prebiotics: mechanisms and health benefits.

PubMed

Slavin, Joanne

2013-04-22

The health benefits of dietary fiber have long been appreciated. Higher intakes of dietary fiber are linked to less cardiovascular disease and fiber plays a role in gut health, with many effective laxatives actually isolated fiber sources. Higher intakes of fiber are linked to lower body weights. Only polysaccharides were included in dietary fiber originally, but more recent definitions have included oligosaccharides as dietary fiber, not based on their chemical measurement as dietary fiber by the accepted total dietary fiber (TDF) method, but on their physiological effects. Inulin, fructo-oligosaccharides, and other oligosaccharides are included as fiber in food labels in the US. Additionally, oligosaccharides are the best known "prebiotics", "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-bring and health." To date, all known and suspected prebiotics are carbohydrate compounds, primarily oligosaccharides, known to resist digestion in the human small intestine and reach the colon where they are fermented by the gut microflora. Studies have provided evidence that inulin and oligofructose (OF), lactulose, and resistant starch (RS) meet all aspects of the definition, including the stimulation of Bifidobacterium, a beneficial bacterial genus. Other isolated carbohydrates and carbohydrate-containing foods, including galactooligosaccharides (GOS), transgalactooligosaccharides (TOS), polydextrose, wheat dextrin, acacia gum, psyllium, banana, whole grain wheat, and whole grain corn also have prebiotic effects.

Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time.

PubMed

Gielkens, H A; van den Biggelaar, A; Vecht, J; Onkenhout, W; Lamers, C B; Masclee, A A

1999-02-01

Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying. To investigate whether intravenous amino acids also influence antroduodenal motility. Eight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test. DCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control. Separate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.

Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes.

PubMed

Hałasa, Maciej; Maciejewska, Dominika; Baśkiewicz-Hałasa, Magdalena; Machaliński, Bogusław; Safranow, Krzysztof; Stachowska, Ewa

2017-04-08

Increased intestinal permeability has been implicated in various pathologies, has various causes, and can develop during vigorous athletic training. Colostrum bovinum is a natural supplement with a wide range of supposed positive health effects, including reduction of intestine permeability. We assessed influence of colostrum supplementation on intestinal permeability related parameters in a group of 16 athletes during peak training for competition. This double-blind placebo-controlled study compared supplementation for 20 days with 500 mg of colostrum bovinum or placebo (whey). Gut permeability status was assayed by differential absorption of lactulose and mannitol (L/M test) and stool zonulin concentration. Baseline L/M tests found that six of the participants (75%) in the colostrum group had increased intestinal permeability. After supplementation, the test values were within the normal range and were significantly lower than at baseline. The colostrum group Δ values produced by comparing the post-intervention and baseline results were also significantly lower than the placebo group Δ values. The differences in stool zonulin concentration were smaller than those in the L/M test, but were significant when the Δ values due to intervention were compared between the colostrum group and the placebo group. Colostrum bovinum supplementation was safe and effective in decreasing of intestinal permeability in this series of athletes at increased risk of its elevation.

Sugars in Antarctic aerosol

NASA Astrophysics Data System (ADS)

Barbaro, Elena; Kirchgeorg, Torben; Zangrando, Roberta; Vecchiato, Marco; Piazza, Rossano; Barbante, Carlo; Gambaro, Andrea

2015-10-01

The processes and transformations occurring in the Antarctic aerosol during atmospheric transport were described using selected sugars as source tracers. Monosaccharides (arabinose, fructose, galactose, glucose, mannose, ribose, xylose), disaccharides (sucrose, lactose, maltose, lactulose), alcohol-sugars (erythritol, mannitol, ribitol, sorbitol, xylitol, maltitol, galactitol) and anhydrosugars (levoglucosan, mannosan and galactosan) were measured in the Antarctic aerosol collected during four different sampling campaigns. For quantification, a sensitive high-pressure anion exchange chromatography was coupled with a single quadrupole mass spectrometer. The method was validated, showing good accuracy and low method quantification limits. This study describes the first determination of sugars in the Antarctic aerosol. The total mean concentration of sugars in the aerosol collected at the ;Mario Zucchelli; coastal station was 140 pg m-3; as for the aerosol collected over the Antarctic plateau during two consecutive sampling campaigns, the concentration amounted to 440 and 438 pg m-3. The study of particle-size distribution allowed us to identify the natural emission from spores or from sea-spray as the main sources of sugars in the coastal area. The enrichment of sugars in the fine fraction of the aerosol collected on the Antarctic plateau is due to the degradation of particles during long-range atmospheric transport. The composition of sugars in the coarse fraction was also investigated in the aerosol collected during the oceanographic cruise.

Gut : liver : brain axis: the microbial challenge in the hepatic encephalopathy.

PubMed

Mancini, Andrea; Campagna, Francesca; Amodio, Piero; Tuohy, Kieran M

2018-03-01

Hepatic encephalopathy (HE) is a debilitating neuropsychiatric condition often associated with acute liver failure or cirrhosis. Advanced liver diseases are characterized by a leaky gut and systemic inflammation. There is strong evidence that the pathogenesis of HE is linked to a dysbiotic gut microbiota and to harmful microbial by-products, such as ammonia, indoles, oxindoles and endotoxins. Increased concentrations of these toxic metabolites together with the inability of the diseased liver to clear such products is thought to play an important patho-ethiological role. Current first line clinical treatments target microbiota dysbiosis by decreasing the counts of pathogenic bacteria, blood endotoxemia and ammonia levels. This review will focus on the role of the gut microbiota and its metabolism in HE and advanced cirrhosis. It will critically assess data from different clinical trials measuring the efficacy of the prebiotic lactulose, the probiotic VSL#3 and the antibiotic rifaximin in treating HE and advanced cirrhosis, through gut microbiota modulation. Additionally data from Randomised Controlled Trials using pre-, pro- and synbiotic will be also considered by reporting meta-analysis studies. The large amount of existing data showed that HE is a clear example of how an altered gut microbiota homeostasis can influence and impact on physiological functions outside the intestine, with implication for host health at the systems level. Nevertheless, a strong effort should be made to increase the information on gut microbiota ecology and its metabolic function in liver diseases and HE.

Prebiotics and synbiotics in ulcerative colitis.

PubMed

Laurell, Axel; Sjöberg, Klas

2017-04-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with unclear pathogenesis. A dysbiotic intestinal microbiota is regarded as a key component in the disease process and there has been significant interest in developing new treatments which target the microbiota. To give an overview of the studies to date investigating prebiotics and synbiotics for the treatment of UC. A literature search of PubMed and related search engines was carried out using the terms "ulcerative colitis" in combination with "prebiotic", "synbiotic" or "dietary fibre". In total 17 studies on humans examining the effect of prebiotics in UC were found. Five major groups could be distinguished. Fructo-oligosaccharides were tried in six studies (mean 35 patients included, range 9-121). One study found a clinical response while two demonstrated indirect evidence of an effect. Germinated barley foodstuff was used in 8 studies (mean 38 patients, range 10-63). One study found an endoscopic response, while four noted a clinical response and two some indirect effects. Galacto-oligosaccharides, lactulose and resveratrol were used in one study each (mean 48 patients, range 41-52). One study found an endoscopic response and one a clinical response. There is yet inadequate evidence - especially in humans - to support any particular prebiotic in the clinical management of UC. However, due to the bulk of evidence supporting the effect of the microbiota on colonic inflammation, there is enough potential to justify further high-quality clinical trials investigating this subject.

Fiber and Prebiotics: Mechanisms and Health Benefits

PubMed Central

Slavin, Joanne

2013-01-01

The health benefits of dietary fiber have long been appreciated. Higher intakes of dietary fiber are linked to less cardiovascular disease and fiber plays a role in gut health, with many effective laxatives actually isolated fiber sources. Higher intakes of fiber are linked to lower body weights. Only polysaccharides were included in dietary fiber originally, but more recent definitions have included oligosaccharides as dietary fiber, not based on their chemical measurement as dietary fiber by the accepted total dietary fiber (TDF) method, but on their physiological effects. Inulin, fructo-oligosaccharides, and other oligosaccharides are included as fiber in food labels in the US. Additionally, oligosaccharides are the best known “prebiotics”, “a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-bring and health.” To date, all known and suspected prebiotics are carbohydrate compounds, primarily oligosaccharides, known to resist digestion in the human small intestine and reach the colon where they are fermented by the gut microflora. Studies have provided evidence that inulin and oligofructose (OF), lactulose, and resistant starch (RS) meet all aspects of the definition, including the stimulation of Bifidobacterium, a beneficial bacterial genus. Other isolated carbohydrates and carbohydrate-containing foods, including galactooligosaccharides (GOS), transgalactooligosaccharides (TOS), polydextrose, wheat dextrin, acacia gum, psyllium, banana, whole grain wheat, and whole grain corn also have prebiotic effects. PMID:23609775

[Prebiotics: concept, properties and beneficial effects].

PubMed

Corzo, N; Alonso, J L; Azpiroz, F; Calvo, M A; Cirici, M; Leis, R; Lombó, F; Mateos-Aparicio, I; Plou, F J; Ruas-Madiedo, P; Rúperez, P; Redondo-Cuenca, A; Sanz, M L; Clemente, A

2015-02-07

Prebiotics are non-digestible food ingredients (oligosaccharides) that reach the colon and are used as substrate by microorganisms producing energy, metabolites and micronutrients used for the host; in addition they also stimulate the selective growth of certain beneficial species (mainly bifidobacteria and lactobacilli) in the intestinal microbiota. In this article, a multidisciplinary approach to understand the concept of prebiotic carbohydrates, their properties and beneficial effects in humans has been carried out. Definitions of prebiotics, reported by relevant international organizations and researchers, are described. A comprehensive description of accepted prebiotics having strong scientific evidence of their beneficial properties in humans (inulin-type fructans, FOS, GOS, lactulose and human milk oligosaccharides) is reported. Emerging prebiotics and those which are in the early stages of study have also included in this study. Taken into account that the chemical structure greatly influences carbohydrates prebiotic properties, the analytical techniques used for their analysis and characterization are discussed. In vitro and in vivo models used to evaluate the gastrointestinal digestion, absorption resistance and fermentability in the colon of prebiotics as well as major criteria to design robust intervention trials in humans are described. Finally, a comprehensive summary of the beneficial effects of prebiotics for health at systemic and intestinal levels is reported. The research effort on prebiotics has been intensive in last decades and has demonstrated that a multidisciplinary approach is necessary in order to claim their health benefits. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Effect of antiorthostatic BedRest (BR) on GastroIntestinal Motility (GIM) of normal subjects

NASA Technical Reports Server (NTRS)

Putcha, L.; Hunter, R. P.; Tietze, K. J.; Cintron, N. M.

1992-01-01

The combined effects of postural changes, fluid shifts and diuresis associated with the absence of the gravity vector may decrease gastrointestinal motility (GIM) during space flight. GIM can be estimated from the mouth to cecum transit time (MCTT) of orally administered lactulose (LAC); this test is used to assess changes in GIM in normal subjects and in patients with GI pathology and related disease conditions. Since bedrest (BR) mimics some of the physiological changes that occur during space flight, the effect of ten days of BR on GIM was evaluated from the MCTT of LAC. Methods: Subjects were 12 nonsmoking males between the ages of 35 and 50. After an 8-10 hour fast, subjects ingested Cephulac (registered) (20 g solution) with a low-fiber breakfast on four different days (45, 30, 25, and 20) before BR and on three separate days (4, 7, and 10) during BR. Breath-H2 concentrations were measured before and at 10 minute intervals for 4 hours after breakfast using a Quintron breathalyzer and MCTT was determined from these data. Results: MCTT ranged between 10 and 122 minutes during ambulation and 80 to 120 minutes during BR with means of 79 minutes and 122 minutes respectively. Conclusion: Mean MCTT during BR was 54 percent longer than during ambulation, suggesting that absorption and availability of orally administered medications and nutrients may be delayed or impaired as a result of decreased GIM during bedrest.

Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments.

PubMed

Nardelli, Silvia; Ridola, Lorenzo; Gioia, Stefania; Riggio, Oliviero

2018-06-01

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. The prevention of HE recurrence, after the first episode of HE, could be obtained by the administration of prophylactic therapy with lactulose, rifaximin or a combination of both. The aim of this review is to clarify some key points in the management of cirrhotic patients with HE, not responsive to first line treatment. Recent studies investigated the role of fecal microbiota transplantation in the treatment of HE with promising results, but further investigations are needed. In a cirrhotic patient with acute cognitive impairment, the correct diagnosis of HE, after excluding other causes of neurological diseases, is mandatory for the correct management of the precipitating factors and for the treatment. In patients not responsive to standard treatment, the probable precipitating factors have not been correctly identified, multiple precipitating events are coexisting or a new precipitating event is superimposed. In some patients with recurrent HE, characterized by persistent alterations in neurological symptoms, without specific precipitants events, the presence of spontaneous or iatrogenic shunts should be investigated.

The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial

PubMed Central

Mujagic, Zlatan; de Vos, Paul; Boekschoten, Mark V.; Govers, Coen; Pieters, Harm-Jan H. M.; de Wit, Nicole J. W.; Bron, Peter A.; Masclee, Ad A. M.; Troost, Freddy J.

2017-01-01

The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gut mucosal gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP104448, TIFN101 or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06 ± 0.04 to 0.10 ± 0.06, p = 0.001), but was not significantly affected by the bacterial interventions. However, analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated gene transcription pathways related to cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific gene transcriptional effects on repair processes in the compromised intestine of healthy subjects. PMID:28045137

Cell culture media supplementation of infrequently used sugars for the targeted shifting of protein glycosylation profiles.

PubMed

Hossler, Patrick; Racicot, Christopher; Chumsae, Christopher; McDermott, Sean; Cochran, Keith

2017-03-01

Mammalian cells in culture rely on sources of carbohydrates to supply the energy requirements for proliferation. In addition, carbohydrates provide a large source of the carbon supply for supporting various other metabolic activities, including the intermediates involved in the protein glycosylation pathway. Glucose and galactose, in particular, are commonly used sugars in culture media for these purposes. However, there exists a very large repertoire of other sugars in nature, and many that have been chemically synthesized. These sugars are particularly interesting because they can be utilized by cells in culture in distinct ways. In the present work it has been found that many infrequently used sugars, and the corresponding cellular response towards them as substrates, led to differences in the protein N-glycosylation profile of a recombinant glycoprotein. The selective media supplementation of raffinose, trehalose, turanose, palatinose, melezitose, psicose, lactose, lactulose, and mannose were found to be capable of redirecting N-glycan oligosaccharide profiles. Despite this shifting of protein glycosylation, there were no other adverse changes in culture performance, including both cell growth and cellular productivity over a wide range of supplemented sugar concentrations. The approach presented highlights a potential means towards both the targeted shifting of protein glycosylation profiles and ensuring recombinant protein comparability, which up to this point in time has remained under-appreciated for these under-utilized compounds. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:511-522, 2017. © 2017 American Institute of Chemical Engineers.

Hepatopedal flow restoration in patients intolerant of total portal diversion.

PubMed Central

Chandler, J G; Fechner, R E

1983-01-01

This report describes an experience with operative restoration of hepatopedal portal blood flow in five patients intolerant of total splanchnic shunting. Portal flow was reestablished by takedown of the total shunt and construction of a selective, distal splenorenal shunt, or by isolation and arterialization of the hepatic limb of the shunted portal vein. In two patients, shunt revision was undertaken electively for chronic encephalopathy, which had been unresponsive to low-protein diet, intestinal antibiosis and oral lactulose. Eighteen and 48 months after operation, both patients have had no encephalopathy on an unrestricted protein intake, and work actively as homemakers. Needle liver biopsies showed enhanced mitotic activity in the early postoperative period, suggesting hepatocyte regeneration. In three patients, shunt conversion or arterialization was undertaken in desperate circumstances, characterized by liver failure (bilirubin greater than 10 mg/dl, albumin less than 2.5 g/dl, prothrombin time greater than 16 sec), coma, and respirator dependency. Although the patients showed immediate, marked improvement in mentation, all three died of intraabdominal hemorrhage in the first few postoperative days, in spite of maximum blood product support. Two conclusions can be drawn from this limited experience: (1) at a time of election, restoration of hepatopedal portal flow can be accomplished with considerable benefit in patients with side-to-side portacaval or hemodynamically equivalent shunts, and (2) similar procedures in patients with fulminant liver failure are unlikely to succeed. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:6847277

Does biological sex impact intestinal epithelial injury, small intestine permeability, gastrointestinal symptoms and systemic cytokine profile in response to exertional-heat stress?

PubMed

Snipe, Rhiannon M J; Costa, Ricardo J S

2018-05-23

This study aimed to determine the influence of biological sex on intestinal injury, permeability, gastrointestinal symptoms, and systemic cytokine profile in response to exertional-heat stress. Male (n= 13) and eumenorrheic female (n= 11) endurance runners completed 2 h running at 60% V̇O 2max in 35°C. Blood samples were collected pre- and post-exercise and during recovery to determine plasma intestinal fatty-acid binding protein (I-FABP) and systemic cytokine profile. Urinary lactulose:L-rhamnose ratio was used to determine small intestine permeability. I-FABP increased 479% pre- to post-exercise (p< 0.001), with no difference between sexes (p= 0.432). No differences between sexes were observed for small intestine permeability (p= 0.808), gut discomfort, total, upper- and lower-gastrointestinal symptoms. However, males reported significantly higher flatulence (p= 0.049) and abdominal stitch (p= 0.025) compared to females. IL-6, IL-8, IL-10 and IL-1ra increased pre- to post-exercise (p< 0.05), with no difference between sexes. However, IL-1β increased post-exercise in males only, and was higher in males compared to females (p= 0.044). Findings suggest that when females are in the follicular phase of the menstrual cycle, biological sex has no effect on intestinal epithelial injury and permeability, and minimal effect on gastrointestinal symptoms and systemic cytokine profile in response to exertional-heat stress.

Review of the treatment options for chronic constipation.

PubMed

Johanson, John F

2007-05-02

Constipation is a common gastrointestinal motility disorder that is often chronic, negatively affects patients' daily lives, and is associated with high healthcare costs. There is a considerable range of treatment modalities available for patients with constipation; however, the clinical evidence supporting their use varies widely. Nonpharmacologic modalities, such as increased exercise or fluid intake and bowel habit training, are generally recommended as first-line approaches, but data on the effectiveness of these measures are limited. The clinical benefits of various traditional pharmacologic agents (many of which are available over the counter, such as laxatives and fiber supplements) remain unclear. Although these modalities may benefit some patients with temporary constipation, their efficacy in patients for whom constipation is chronic is less well defined. Some studies suggest benefit with psyllium, polyethylene glycol, and lactulose; however, the use of other agents, such as calcium polycarbophil, methylcellulose, bran, magnesium hydroxide, and stimulant laxatives, is not supported by strong clinical evidence. More recently, newer agents have been approved for the treatment of patients with chronic constipation on the basis of comprehensive clinical investigation programs. Tegaserod, with its well-established clinical profile, and lubiprostone, the latest addition to the treatment armamentarium, represent the new generation of therapies for chronic constipation. This article reviews the efficacy and safety of traditional therapies used in the management of the multiple symptoms associated with chronic constipation and discusses recently approved and emerging therapies for this disorder.

Interactions between drugs and drug-nutrient in enteral nutrition: a review based on evidences.

PubMed

Ferreira Silva, Renata; Rita Carvalho Garbi Novaes, Maria

2014-09-01

Enteral nutrition (EN) provides calories, macronutrients and micronutrients in adequate quantity and quality to meet the patient's needs. Some drugs when crushed and diluted may have their properties altered, including the reduction of bioavailability causing the reduction of the serum concentration of the drug; tube obstruction; drug-drug interaction or drug-nutrient interaction. The study was conducted through review of submitted articles in the databases of the Virtual Health Library (VHL): MEDLINE (National Library of Medicine, USA), Lilacs (Latin American and Caribbean Literature on Health Sciences) PUBMED - NCBI (National Center for Biotechnology Information) and COCHRANE. For this survey, 42 articles were identified during database searching. After applying the inclusion and exclusion criteria, 08 articles were selected, obtained from the MEDLINE and Lilacs. Some interactions were found such as the aluminium hydroxide and lactulose with the enteral nutrition, which may result in a precipitation and reduction of drug bioavailability. Mineral oil will alter the absorption of fat-soluble vitamins and reduces the tube light. Others results were found as phenytoin, warfarin, captopril and furosemide with enteral nutrition may reduce the maximum serum concentration. Drug interactions are more common in day-to-day activities than health professionals may suppose. Knowledge on the matter may also assist in reducing cases of obstruction of tubes, through which enteral nutrition and medications are administered. Thus, the multidisciplinary team, acting together, may have more beneficial effects to the patient. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Dielectric studies on mobility of the glycosidic linkage in seven disaccharides.

PubMed

Kaminski, K; Kaminska, E; Wlodarczyk, P; Pawlus, S; Kimla, D; Kasprzycka, A; Paluch, M; Ziolo, J; Szeja, W; Ngai, K L

2008-10-09

Isobaric dielectric relaxation measurements were performed on seven chosen disaccharides. For five of them, i.e., sucrose, maltose, trehalose, lactulose, and leucrose, we were able to observe the temperature evolution of the structural relaxation process. In the case of the other disaccharides studied (lactose and cellobiose), it was impossible to obtain such information because of the large contribution of the dc conductivity and polarization of the capacitor plates to the imaginary and real part of the complex permittivity, respectively. On the other hand, in the glassy state, two secondary relaxations have been identified in the dielectric spectra of all investigated carbohydrates. The faster one (gamma) is a common characteristic feature of the entire sugar family (mono-, di-, oligo-, and polysaccharide). The molecular origin of this process is still not unambiguously identified but is expected to involve intramolecular degrees of freedom as inferred from insensitivity of its relaxation time to pressure found in some monosaccharides (fructose and ribose). The slower one (labeled beta) was recently identified to be intermolecular in origin (i.e., a Johari-Goldstein (JG) beta-relaxation), involving twisting motion of the monosugar rings around the glycosidic bond. The activation energies and dielectric strengths for the beta-relaxation determined herein provide us valuable information about the flexibility of the glycosidic bond and the mobility of this particular linkage in the disaccharides studied. In turn, this information is essential for the control of the diffusivity of drugs or water entrapped in the sugar matrix.

Probiotics for people with hepatic encephalopathy.

PubMed

Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C

2017-02-23

Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration

In vitro fermentation of oat flours from typical and high beta-glucan oat lines.

PubMed

Kim, Hyun Jung; White, Pamela J

2009-08-26

Two publicly available oat (Avena sativa) lines, "Jim" and "Paul" (5.17 and 5.31% beta-glucan, respectively), and one experimental oat line "N979" (7.70% beta-glucan), were used to study the effect of beta-glucan levels in oat flours during simulated in vitro digestion and fermentation with human fecal flora obtained from different individuals. The oat flours were digested by using human digestion enzymes and fermented by batch fermentation under anaerobic conditions for 24 h. The fermentation progress was monitored by measuring pH, total gas, and short-chain fatty acid (SCFA) production. Significant effects of beta-glucan on the formation of gas and total SCFA were observed compared to the blank without substrate (P < 0.05); however, there were no differences in pH changes, total gas, and total SCFA production among oat lines (P > 0.05). Acetate, propionate, and butyrate were the main SCFA produced from digested oat flours during fermentation. More propionate and less acetate were produced from digested oat flours compared to lactulose. Different human fecal floras obtained from three healthy individuals had similar patterns in the change of pH and the production of gas during fermentation. Total SCFA after 24 h of fermentation were not different, but the formation rates of total SCFA differed between individuals. In vitro fermentation of digested oat flours with beta-glucan could provide favorable environmental conditions for the colon and these findings, thus, will help in developing oat-based food products with desirable health benefits.

Effects of enteral immunonutrition on the maintenance of gut barrier function and immune function in pigs with severe acute pancreatitis.

PubMed

Zou, Xiao-Ping; Chen, Min; Wei, Wei; Cao, Jun; Chen, Lei; Tian, Mi

2010-01-01

This study evaluated the effects of enteral immunonutrition (EIN) supplemented with glutamine, arginine, and probiotics on gut barrier function and immune function in pigs with severe acute pancreatitis (SAP). The model was induced by retrograde injection of 5% sodium taurocholate and trypsin via the pancreatic duct. After induction of SAP, 18 pigs were randomly divided into 3 groups, in which either parenteral nutrition (PN), control enteral nutrition (CEN), or EIN was applied for 8 days. Serum and pancreatic fluid amylase concentration was determined. Intestinal permeability (lactulose to mannitol ratio) was measured by high-performance liquid chromatography, and plasma endotoxin was quantified by the chromogenic limulus amebocyte lysate technique. Samples of venous blood and organs were cultured using standard techniques. Pancreatitis severity and villi of ileum were scored according to histopathologic grading. Plasma T-lymphocyte subsets were measured by flow cytometry, and immunoglobulins (Igs) were determined via enzyme-linked immunosorbent assay. There were no significant differences in serum and pancreatic fluid amylases concentrations or in pancreatitis severity between any 2 of the 3 groups. Compared with PN and CEN, EIN significantly decreased intestinal permeability, plasma endotoxin concentration, and the incidence and magnitudes of bacterial translocation, but increased ileal mucosal thickness, villous height, crypt depth, and percentage of normal intestinal villi. Significant differences were found in CD3+, CD4+ lymphocyte subsets, the ratio of CD4+: CD8+ lymphocyte subsets, and serum IgA and IgG, but not IgM, between any 2 of the 3 groups. EIN maintained gut barrier function and immune function in pigs with SAP.

Effects of added fermentable carbohydrates in the diet on intestinal proinflammatory cytokine-specific mRNA content in weaning piglets.

PubMed

Pié, S; Awati, A; Vida, S; Falluel, I; Williams, B A; Oswald, I P

2007-03-01

There is increasing evidence showing that dietary supplementation with prebiotics can be effective in the treatment of intestinal inflammation. Because weaning time is characterized by rapid intestinal inflammation, this study investigated the effect of a diet supplemented with a combination of 4 fermentable carbohydrates (lactulose, inulin, sugarbeet pulp, and wheat starch) on the mRNA content of proinflammatory cytokines in newly weaned piglets. Cytokines (IL-1beta, IL-6, IL-8, IL-12p40, IL-18, and tumor necrosis factor-alpha) were analyzed using a semiquantitative reverse-transcription PCR technique on d 1, 4, and 10 in the ileum and colon of piglets fed either a test diet (CHO) or a control diet. In addition to the diet, the effect of enforced fasting on cytokine mRNA content was also evaluated. No effect of fasting was observed on the pro-inflammatory cytokine mRNA content. Our results showed that the CHO diet induced an up-regulation of IL-6 mRNA content in the colon of piglets 4 d postweaning. This up-regulation was specific for the animals fed the CHO diet and was not observed in animals fed the control diet. An increase in IL-1beta mRNA content was also observed on d 4 postweaning in all of the piglets. Correlations between proinflammatory cytokines and the end-products of fermentation indicated that the regulation of cytokines may be linked with some of the fermentation end-products such as branched-chain fatty acids, which are in turn end-products of protein fermentation.

Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

NASA Technical Reports Server (NTRS)

Vaksman, Z.; Guthienz, J.; Putcha, L.

2008-01-01

Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

Combinational effects of prebiotic oligosaccharides on bifidobacterial growth and host gene expression in a simplified mixed culture model and neonatal mice.

PubMed

Ehara, Tatsuya; Izumi, Hirohisa; Tsuda, Muneya; Nakazato, Yuki; Iwamoto, Hiroshi; Namba, Kazuyoshi; Takeda, Yasuhiro

2016-07-01

It is important to provide formula-fed infants with a bifidobacteria-enriched gut microbiota similar to those of breastfed infants to ensure intestinal health. Prebiotics, such as certain oligosaccharides, are a useful solution to this problem, but the combinational benefits of these oligosaccharides have not been evaluated. This study investigated the benefits of oligosaccharide combinations and screened for an optimal combination of oligosaccharides to promote healthy gut microbiota of formula-fed infants. In vitro and in vivo experiments were performed to assess the bifidogenic effects of lactulose (LAC) alone and LAC combined with raffinose (RAF) and/or galacto-oligosaccharide (GOS), using a mixed culture model and neonatal mice orally administered with these oligosaccharides and Bifidobacterium breve. In the in vitro culture model, the combination of the three oligosaccharides (LAC-RAF-GOS) significantly increased cell numbers of B. breve and Bifidobacterium longum (P<0·05) compared with either LAC alone or the combination of two oligosaccharides, and resulted in the production of SCFA under anaerobic conditions. In the in vivo experiment, the LAC-RAF-GOS combination significantly increased cell numbers of B. breve and Bacteroidetes in the large intestinal content (P<0·05) and increased acetate concentrations in the caecal content and serum of neonatal mice. Genes related to metabolism and immune responses were differentially expressed in the liver and large intestine of mice administered with LAC-RAF-GOS. These results indicate a synergistic effect of the LAC-RAF-GOS combination on the growth of bifidobacteria and reveal possible benefits of this combination to the gut microbiota and health of infants.

The impact of alcohol consumption and cholecystectomy on small intestinal bacterial overgrowth.

PubMed

Gabbard, Scott L; Lacy, Brian E; Levine, Gary M; Crowell, Michael D

2014-03-01

The etiology of small intestinal bacterial overgrowth (SIBO) is diverse and frequently multi-factorial. SIBO is thought to result from structural changes of the gastrointestinal tract, disordered peristalsis of the stomach and/or small intestine, or a disruption of the normal mucosal defenses of the small intestine. Alcoholics are reported to have higher rates of SIBO, as diagnosed by jejunal aspirate; however, no data are available on the association between moderate alcohol consumption and SIBO. To evaluate the association between moderate alcohol consumption and SIBO and identify risk factors for SIBO using the lactulose breath test (LBT). A retrospective chart review was completed for 210 consecutive patients who underwent the LBT between 2008 and 2010. We reviewed demographic data, including age, race, body mass index, alcohol and tobacco history, medication use, comorbid medical conditions, and history of abdominal surgery. The study included 196 patients (68 % female; mean age 55 years), 93 of whom had a positive LBT (47.4 %). Of those patients who consumed a moderate amount of alcohol, 58 % had a positive LBT, compared to 38.9 % of abstainers (P = 0.008). Those with a history of cholecystectomy had significantly lower rates of a positive LBT than those who had not (33.3 vs. 51.7 % respectively; P = 0.031). Neither proton pump inhibitor (PPI) use nor tobacco use was associated with a positive LBT. In this retrospective review, moderate alcohol consumption was a strong risk factor for SIBO. Cholecystectomy appeared to be protective against SIBO. Neither PPI use nor tobacco use was associated with an increased risk of SIBO.

Small intestinal bacterial overgrowth syndrome

PubMed Central

Bures, Jan; Cyrany, Jiri; Kohoutova, Darina; Förstl, Miroslav; Rejchrt, Stanislav; Kvetina, Jaroslav; Vorisek, Viktor; Kopacova, Marcela

2010-01-01

Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID:20572300

Delayed small intestinal transit in patients with long-standing type 1 diabetes mellitus: investigation of the relationships with clinical features, gastric emptying, psychological distress, and nutritional parameters.

PubMed

Faria, Mariza; Pavin, Elizabeth João; Parisi, Maria Cândida Ribeiro; Lorena, Sônia Letícia Silva; Brunetto, Sérgio Quirino; Ramos, Celso Dario; Pavan, Célia Regina; Mesquita, Maria Aparecida

2013-01-01

Studies on small intestinal transit in type 1 diabetes mellitus have reported contradictory results. This study assessed the orocecal transit time (OCTT) in a group of patients with type 1 diabetes mellitus and its relationships with gastrointestinal symptoms, glycemic control, chronic complications of diabetes, anthropometric indices, gastric emptying, small intestinal bacterial overgrowth (SIBO), and psychological distress. Twenty-eight patients with long-standing (>10 years) type 1 diabetes mellitus (22 women, six men; mean age, 39 ± 9 years) participated in the study. The lactulose hydrogen breath test was used to determine OCTT and the occurrence of SIBO. The presence of anxiety and depression was assessed by the Hospital Anxiety and Depression scale. Gastric emptying was measured by scintigraphy. Anthropometric indices included body mass index, percentage body fat, midarm circumference, and arm muscle area. There was a statistically significant increase in OCTT values in diabetes patients (79 ± 41 min) in comparison with controls (54 ± 17 min) (P=0.01). Individual analysis showed that OCTT was above the upper limit (mean+2 SD) in 30.8% of patients. All anthropometric parameters were significantly decreased (P<0.05) in patients with prolonged OCTT in comparison with those with normal OCTT. In contrast, there was no statistically significant association between prolonged OCTT and gastrointestinal symptoms, peripheral neuropathy, diabetic retinopathy, glycated hemoglobin, delayed gastric emptying, SIBO, anxiety, or depression. Small bowel transit may be delayed in about one-third of patients with long-standing type 1 diabetes mellitus. This abnormality seems to have a negative effect on nutritional status in these patients.

A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome.

PubMed

Xiao, Shuiming; Fei, Na; Pang, Xiaoyan; Shen, Jian; Wang, Linghua; Zhang, Baorang; Zhang, Menghui; Zhang, Xiaojun; Zhang, Chenhong; Li, Min; Sun, Lifeng; Xue, Zhengsheng; Wang, Jingjing; Feng, Jie; Yan, Feiyan; Zhao, Naisi; Liu, Jiaqi; Long, Wenmin; Zhao, Liping

2014-02-01

Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes. © 2013 The Authors. FEMS Microbiology Ecology pubished by John Wiley & Sons Ltd on behalf of the Federation of European Microbiological Societies.

Carbamazepine-induced hyperammonemia.

PubMed

Adams, Erin N; Marks, Alla; Lizer, Mitsi H

2009-08-15

A case of carbamazepine-induced hyperammonemia is presented. A 26-year-old man with bipolar disorder, seizures, and mild mental retardation secondary to a traumatic brain injury began treatment with carbamazepine for aggression and seizure control. After three weeks of carbamazepine therapy, the patient arrived at the emergency department (ED) with severe agitation and aggressive behavior. His oral medications included topiramate, carbamazepine, olanzapine, quetiapine, guanfacine, and desmopressin acetate. The patient's medications had been stable for at least six months except for the addition of carbamazepine one month before his arrival at the ED. Upon admission, the patient's vital signs were found to be within normal limits, as were his liver profile results, complete blood count, thyroid-stimulating-hormone level, and serum chemistry panel. His serum carbamazepine concentration was 3.9 microg/mL (reference range, 4-12 microg/mL), and his serum ammonia concentration was 127 microg/dL (reference range, 19-60 microg/dL). Carbamazepine was discontinued upon admission, and the patient was treated with oral lactulose. Since carbamazepine was discontinued and had been prescribed for bipolar disorder, his olanzapine dosage was increased, and trazodone was added at bedtime for insomnia. Of note, the patient had been on carbamazepine therapy one year earlier and had experienced the same adverse event. He had also developed elevated serum ammonia levels while on valproic acid. The patient's serum ammonia level returned to normal by hospital day 4, and he was discharged to his group home. A 26-year-old man with bipolar disorder developed hyperammonemia three weeks after initiating carbamazepine therapy.

Effect of Safflower Oil on Concentration of Conjugated Linoleic Acid of Kefir Prepared by Low-fat Milk.

PubMed

Farsad-Naeimi, Alireza; Imani, Saeid; Arefhosseini, Seyed R; Alizadeh, Mohammad

2015-01-01

Conjugated linoleic acid (CLA) is a special fatty acid in dairy products with unique antioxidant and anti-cancerous effects. Kefir, a milk product, comprises normalized homogenized cow's milk, the fructose and lactulose syrup as well as a symbiotic starter which has improved probiotic characteristics. The study was aimed to discuss patents and to examine the effect of different safflower oil concentrations on CLA content of the kefir drink prepared by low-fat milk. Safflower oil was added at 0.1, 0.3 and 0.5% (V/V) to low-fat cow's milk and six formulations of kefir samples were prepared. The CLA content of the kefir products was measured at pH=6.0 and pH=6.8 by gas chromatography. Acid and bile tolerance of bacterial microenvironment in the products were also determined. Substitution of natural fat content of milk with safflower oil resulted in proportional increase in the CLA contents of kefir in a dose dependent manner. The highest concentration of CLA was found under 0.5% (V/V) of safflower oil at pH 6.0 and temperature of 37 °C. Adding the Safflower oil into milk used for kefir production, increased CLA content from 0.123 (g/100 g) in pure safflower free samples to 0.322 (g/100 g) in samples with 0.5% (V/V) of safflower oil. The current study revealed that substitution of safflower oil with natural fat of cow's milk may help the production of kefir samples with remarkable increase in CLA content of final product.

Isolation and characterization of two new homoacetogenic hydrogen-utilizing bacteria from the human intestinal tract that are closely related to Clostridium coccoides.

PubMed Central

Kamlage, B; Gruhl, B; Blaut, M

1997-01-01

Two gram-positive, strictly anoxic, coccoid- to rod-shaped strains of bacteria, Clostridium coccoides 1410 and C. coccoides 3110, were isolated from human feces on the typical homoacetogenic substrates formate plus H2 plus CO2 (strain 1410) and vanillate plus H2 plus CO2 (strain 3110) in the presence of 2-bromoethanesulfonate to inhibit methanogenesis. On the basis of 16S rRNA sequencing, DNA-DNA hybridization, and physiological and morphological parameters, both isolates are closely related to C. coccoides DSM 935T. The G+C contents of the DNA were 46.1 and 46.2 mol% for C. coccoides 1410 and C. coccoides 3110, respectively. Cytochromes could not be detected. Formate was degraded exclusively to acetate, whereas vanillate was O-demethylated, resulting in acetate and 3,4-dihydroxybenzoate, the latter being further decarboxylated to catechol. In the presence of organic substrates, H2 was cometabolized to acetate, but both strains failed to grow autotrophically. Lactose, lactulose, sorbitol, glucose, and various other carbohydrates supported growth as well. Untypical of homoacetogens, glucose and sorbitol were fermented not exclusively to acetate; instead, considerable amounts of succinate and D-lactate were produced. H2 was evolved from carbohydrates only in negligible traces. Acetogenesis from formate plus H2 plus CO2 or vanillate plus H2 plus CO2 was constitutive, whereas utilization of carbohydrates was inducible. Hydrogenase, CO dehydrogenase, formate dehydrogenase, and all of the tetrahydrofolic acid-dependent, C1 compound-converting enzymes of the acetyl-coenzyme A pathway of homoacetogenesis were present in cell extracts. PMID:9143110

Isolation and characterization of two new homoacetogenic hydrogen-utilizing bacteria from the human intestinal tract that are closely related to Clostridium coccoides.

PubMed

Kamlage, B; Gruhl, B; Blaut, M

1997-05-01

Two gram-positive, strictly anoxic, coccoid- to rod-shaped strains of bacteria, Clostridium coccoides 1410 and C. coccoides 3110, were isolated from human feces on the typical homoacetogenic substrates formate plus H2 plus CO2 (strain 1410) and vanillate plus H2 plus CO2 (strain 3110) in the presence of 2-bromoethanesulfonate to inhibit methanogenesis. On the basis of 16S rRNA sequencing, DNA-DNA hybridization, and physiological and morphological parameters, both isolates are closely related to C. coccoides DSM 935T. The G+C contents of the DNA were 46.1 and 46.2 mol% for C. coccoides 1410 and C. coccoides 3110, respectively. Cytochromes could not be detected. Formate was degraded exclusively to acetate, whereas vanillate was O-demethylated, resulting in acetate and 3,4-dihydroxybenzoate, the latter being further decarboxylated to catechol. In the presence of organic substrates, H2 was cometabolized to acetate, but both strains failed to grow autotrophically. Lactose, lactulose, sorbitol, glucose, and various other carbohydrates supported growth as well. Untypical of homoacetogens, glucose and sorbitol were fermented not exclusively to acetate; instead, considerable amounts of succinate and D-lactate were produced. H2 was evolved from carbohydrates only in negligible traces. Acetogenesis from formate plus H2 plus CO2 or vanillate plus H2 plus CO2 was constitutive, whereas utilization of carbohydrates was inducible. Hydrogenase, CO dehydrogenase, formate dehydrogenase, and all of the tetrahydrofolic acid-dependent, C1 compound-converting enzymes of the acetyl-coenzyme A pathway of homoacetogenesis were present in cell extracts.

Small Intestinal Bacterial Overgrowth May Increase the Likelihood of Lactose and Sorbitol but not Fructose Intolerance False Positive Diagnosis.

PubMed

Perets, Tsachi Tsadok; Hamouda, Dalal; Layfer, Olga; Ashorov, Olga; Boltin, Doron; Levy, Sigal; Niv, Yaron; Dickman, Ram

2017-08-01

Small intestinal bacterial overgrowth (SIBO) is defined as a bacterial count of more than 10 5 colony-forming units per milliliter in duodenal aspirate. It shares many symptoms with carbohydrate intolerance, which makes the clinical distinction of the disorders difficult. The aim of the study was to examine the relationship between a positive carbohydrate breath test and the presence of SIBO suggested by a positive lactulose hydrogen breath test. The electronic database of the gastroenterology laboratory of a tertiary medical center was searched for all patients clinically tested for SIBO in 2012-2013 for whom previous results for lactose, fructose, and/or sorbitol breath test were available. The correlation between positive findings for carbohydrate intolerance and for SIBO was statistically analyzed. The study group included 349 patients, 231 female and 118 male, of mean age 53±19 years. All had symptoms of abdominal bloating and gas. There was a statistically significant difference in rates of a positive breath test for lactose and sorbitol at ≤90 minutes between patients who were positive and negative for SIBO [χ 2 (1)=12.8, p <0.01 and χ 2 (1)=9.5, p <0.01 respectively]. Findings for fructose were not significant. There was no effect of age or gender. SIBO may represent an important reversible cause of carbohydrate intolerance. It may be especially prudent to exclude SIBO patients with an early peak (≤90 minutes) in H 2 excretion. © 2017 by the Association of Clinical Scientists, Inc.

Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non-alcoholic steatohepatitis

PubMed Central

Farhadi, Ashkan; Gundlapalli, Sushama; Shaikh, Maliha; Frantzides, Constantine; Harrell, Laura; Kwasny, Mary M.; Keshavarzian, Ali

2014-01-01

Introduction One of the proposed second hit mechanisms in the pathophysiology of non-alcoholic steatohepatitis (NASH) is hepatic oxidative stress triggered by elevated levels of endotoxin. We investigated one possible mechanism for the endotoxaemia – disruption of intestinal barrier integrity. Methods We enrolled 16 subjects with fatty liver (10 NASH; 6 steatosis) and 12 healthy subjects. Steatosis and NASH were diagnosed by liver biopsy using the Brunt criteria. Gastrointestinal permeability was measured using urinary excretion of 5-h lactulose/mannitol (L/M) ratio and 24-h sucralose. Permeability testing was repeated after aspirin challenge. Results Groups had similar baseline urinary 0–5 h L/M ratio (small bowel permeability) and 0–24 h sucralose (whole-gut permeability). Aspirin increased 0–5 h urinary L/M in most subjects. In contrast, aspirin significantly increased whole-gut permeability only in NASH subjects. In fact, the major increase in the urinary sucralose occurred in the 6–24 h samples, which points towards the colon as the major site responsible for aspirin-induced leakiness in NASH patients. Serum endotoxin levels were significantly higher in NASH subjects. Discussion Our findings suggest that aspirin acts on the colon to unmask a susceptibility to gut leakiness in patients with NASH. This effect may be the underlying mechanism for increased serum endotoxin, which is the second hit (after altered lipid metabolism) that is required to initiate a necroinflammatory cascade in hepatocytes which are already primed with obesity-induced abnormal lipid homoeostasis. PMID:18397235

Colonic obstruction secondary to sigmoid fecaloma endoscopically resolved with Coca-Cola®.

PubMed

Ontanilla Clavijo, Guillermo; León Montañés, Rafael; Sánchez Torrijos, Yolanda; López Ruiz, Teófilo; Bozada García, Juan Manuel

2017-04-01

Colonic obstruction is a relatively common condition in emergency care, with a mortality rate of up to 20%. In 90% of cases it results from colonic or rectal adenocarcinoma, volvulus, or stenosis secondary to diverticular disease. When fecal impaction is the underlying cause, the condition is usually managed conservatively, but may on occasion become complicated and even require surgical intervention. Based on the proven efficacy of Coca-Cola® to dissolve gastric phytobezoars, we report a case of colonic obstruction secondary to sigmoid fecaloma. A 58 years old woman arrived at the Emergency Room (ER) with persistent constipation for the last six days. An abdominal CT scan showed a large fecal mass at the sigmoid colon with retrograde dilated colonic loops. Cleansing enemas and oral lactulose were administered, which failed to resolve the clinical presentation, so we then proceeded to inject Coca-Cola® within the fecaloma using a sclerosing needle, and then washed the fecaloma surface also with Coca-Cola®. After a few minutes we started to fragment the fecalith, the consistency of which had been notably decreased. The use of Coca-Cola® for gastric washes in the management of phytobezoars is well established. Since fecaliths are partly composed of these same substances than phytobezoars, the use of Coca-Cola® might well be warranted against them as in our patient, without surgery. Our case report is the second one published in the literature, in which Coca-Cola® helped solve colonic obstruction secondary to fecaloma.

Glutamine Supplementation of Parenteral Nutrition Does Not Improve Intestinal Permeability, Nitrogen Balance, or Outcome in Newborns and Infants Undergoing Digestive-Tract Surgery

PubMed Central

Albers, Marcel J. I. J.; Steyerberg, Ewout W.; Hazebroek, Frans W. J.; Mourik, Marjan; Borsboom, Gerard J. J. M.; Rietveld, Trinet; Huijmans, Jan G. M.; Tibboel, Dick

2005-01-01

Objective: To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery. Summary Background Data: Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results. Methods: Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg−1 day−1; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources. Results: Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects. Conclusions: In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise. PMID:15798461

Impact of intestinal mannitol on hyperammonemia, oxidative stress and severity of hepatic encephalopathy in the ED.

PubMed

Montes-Cortés, Daniel H; Novelo-Del Valle, José L; Olivares-Corichi, Ivonne M; Rosas-Barrientos, José V; Jara, Luis J; Cruz-Domínguez, María Pilar

2018-01-10

Hyperammonemia results from hepatic inability to remove nitrogenous products generated by protein metabolism of intestinal microbiota, which leads to hepatic encephalopathy (HE) in chronic liver disease (CLD). In ammonium neurotoxicity, oxidative stress (OxS) plays a pathogenic role. Our objective was to evaluate if intestinal mannitol is as effective and safe as conventional treatment for diminishing hyperammonemia, OxS, and HE in patients with CLD. We included 30 patients with HE classified by "Haven Criteria for Hepatic Encephalopathy". They were randomized into two groups: 1) Mannitol Group (MG) with mannitol 20% administered into the intestine by an enema, 2) conventional group (CG) with lactulose 40 g enema both substances were diluted in 800 mL of double distilled solution every 6 h; all patients received neomycin. We evaluated ammonia concentration, plasma oxidative stress, HE severity, intestinal discomfort and adverse effects. Hyperammonemia (171 ± 104 vs 79 ± 49 μmol ammonia/L, p < 0.01), and oxidative stress (MDA 29 vs 27%, formazan 15 vs 11%, carbonyls 16 vs 9% and dityrosines 10 vs 5%) were reduced in MG and CG respectively. The HE severity decreased by two degrees compared to baseline values in both groups. Intestinal discomfort and electrolyte plasma alterations were less frequent (p < 0.05) in MG than CG. Intestinal mannitol is as effective and safe as conventional treatment for reducing hyperammonemia, oxidative stress, and hepatic encephalopathy of CLD patients in the emergency room. Likewise, mannitol is better tolerated than conventional treatment. Copyright © 2018. Published by Elsevier Inc.

The scintigraphic determination of small intestinal transit time in patients with irritable bowel syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marano, A.R.; Caride, V.J.; Shah, R.V.

1984-01-01

Diffuse disturbance in gastrointestinal motility may be present in patients with irritable bowel syndrome (IBS). To further investigate small intestinal motility in IBS patients small intestinal transit time (SITT) was determined and related to the symptom status. 11 female patients with IBS (mean age 29 years) were divided into those whose predominate symptom was diarrhea (N=6), and those with only constipation (N=5). All subjects ingested an isosmotic solution of lactulose (10 gm in 150cc of water) labeled with 99m-Tc-DTPA (Sn). The patient was studied supine under a 25 inch gamma camera with data collected at 1 frame per minute formore » 180 minutes or until activity appeared in the ascending colon. Regions of interest were selected over the cecum and ascending colon. The time of first appearance of radioactivity in the region of the cecum was taken as the small intestinal transit time. SITT in the 5 normal females was 98.7 +- 13 min (mean +- SEM). SITT in the IBS patients with diarrhea, 67.3 +- 7 min was significantly faster (p< 0.08). SITT in the constipated IBS patients, 126 +- 12 min, was slower than normals and significantly different from diarrhea patients (p< 0.001). These studies show that IBS patients with diarrhea have significantly faster SITT than normals while constipated IBS patients have significantly slower SITT than the diarrhea subgroup. Further, this study emphasizes the need to study the various symptomatic subgroups of IBs patients independently and indicates a possible role for abnormal SITT in the pathogenesis of IBS.« less

Celiac disease: management of persistent symptoms in patients on a gluten-free diet.

PubMed

Dewar, David H; Donnelly, Suzanne C; McLaughlin, Simon D; Johnson, Matthew W; Ellis, H Julia; Ciclitira, Paul J

2012-03-28

To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years. One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.

Determinant Variables, Enteric Pathogen Burden, Gut Function and Immune-related Inflammatory Biomarkers Associated With Childhood Malnutrition: A Prospective Case-Control Study in Northeastern Brazil.

PubMed

Lima, Aldo A M; Leite, Álvaro M; Di Moura, Alessandra; Lima, Noélia L; Soares, Alberto M; Abreu, Cláudia B; Filho, José Quirino; Mota, Rosa M S; Lima, Ila F N; Havt, Alexandre; Medeiros, Pedro H Q S; Prata, Mara M G; Guedes, Marjorie M; Cavalcante, Paloma A; Veras, Herlice N; Santos, Ana K S; Moore, Sean R; Pinkerton, Relana C; Houpt, Eric R; Guerrant, Richard L

2017-12-01

Malnutrition results in serious consequences for growth and cognitive development in children. We studied select child and maternal biologic factors, socioeconomic factors, enteric pathogenic burden and gut function biomarkers in 402 children 6-24 months of age in Northeastern Brazil. In this prospective case-control study, not being fed colostrum [odds ratio (OR): 3.29, 95% confidence interval (CI): 1.73-6.26], maternal age ≥18 years (OR: 1.88, 95% CI: 1.10-3.22) and no electric fan (OR: 2.46, 95% CI: 1.22-4.96) or bicycle (OR: 1.80, 95% CI: 1.10-2.95) in the household were positively associated, and higher birth weight (OR: 0.27, 95% CI: 0.19-0.38), larger head circumference (OR: 0.74, 95% CI: 0.66-0.82) and shortness of breath in the last 2 weeks (OR: 0.49, 95% CI: 0.27-0.90) were negatively associated with malnutrition. Subclinical enteric pathogen infections were common, and enteroaggregative Escherichia coli infections were more prevalent in malnourished children (P = 0.045). Biomarkers such as the lactulose-mannitol test, myeloperoxidase, neopterin and calprotectin were highly elevated in both malnourished and nourished children. Nourished children had a better systemic immune response than the malnourished children, as detected by elevated serum amyloid A-1 and soluble cluster of differentiation protein 14 biomarkers (P < 0.001). Serum amyloid A-1 and soluble cluster of differentiation protein 14 were also associated with better nutritional Z scores. Neonatal, maternal and socioeconomic factors were associated with malnutrition in children. There was a substantial subclinical enteric pathogen burden, particularly with enteroaggregative E. coli, in malnourished children.

Chlorogenic Acid Decreases Intestinal Permeability and Increases Expression of Intestinal Tight Junction Proteins in Weaned Rats Challenged with LPS

PubMed Central

Ruan, Zheng; Liu, Shiqiang; Zhou, Yan; Mi, Shumei; Liu, Gang; Wu, Xin; Yao, Kang; Assaad, Houssein; Deng, Zeyuan; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

2014-01-01

Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA) could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS) challenge. Thirty-two weaned male Sprague Dawley rats (21±1 d of age; 62.26±2.73 g) were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA) supplemented group (orally 20 mg/kg and 50 mg/kg body). Dietary supplementation with CHA decreased (P<0.05) the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05) in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05) villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05) intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05) by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05) in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS. PMID:24887396

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents.

PubMed

Nicaise, Charles; Prozzi, Deborah; Viaene, Eric; Moreno, Christophe; Gustot, Thierry; Quertinmont, Eric; Demetter, Pieter; Suain, Valérie; Goffin, Philippe; Devière, Jacques; Hols, Pascal

2008-10-01

Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed. Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut.

Assessment of the Intestinal Barrier with Five Different Permeability Tests in Healthy C57BL/6J and BALB/cJ Mice.

PubMed

Volynets, Valentina; Reichold, Astrid; Bárdos, Gyöngyi; Rings, Andreas; Bleich, André; Bischoff, Stephan C

2016-03-01

Intestinal permeability is thought to be of major relevance for digestive and nutrition-related diseases, and therefore has been studied in numerous mouse models of disease. However, it is unclear which tools are the preferable ones, and how normal values should be defined. To compare different in vivo permeability tests in healthy mice of commonly used genetic backgrounds. We assessed the intestinal barrier in male and female C57BL/6J and BALB/cJ mice of different ages, using four orally administered permeability markers, FITC-dextran 4000 (FITC-D4000) and ovalbumin (OVA) measured in plasma, and polyethylene glycol (PEG) and lactulose/mannitol (Lac/Man) measured in urine, and by assessing lipopolysaccharide (LPS) in portal vein plasma. After gavage, FITC-D4000, OVA, Lac/Man, and PEG400, but not PEG4000, were detectable in plasma or urine. Female mice tended to have a higher permeability according to the FITC-D4000, OVA, and PEG400 tests, but the Lac/Man ratio was higher in males. No significant differences between the two mouse strains of young and old mice were observed except for mannitol recovery, which was higher in BALB/cJ mice compared to C57BL/6J mice (p < 0.05). Virtually no LPS was detected in healthy mice. For all markers, normal values have been defined based on 5th-95th percentile ranges of our data. Selected oral permeability tests, such as FITC-D4000, OVA, PEG400, and Lac/Man, as well as LPS measurements in portal vein plasma, could be suitable for the evaluation of the intestinal barrier in mice, if used in a standardized way.

Translational safety biomarkers of colonic barrier integrity in the rat.

PubMed

Erkens, Tim; Bueters, Ruud; van Heerden, Marjolein; Cuyckens, Filip; Vreeken, Rob; Goeminne, Nick; Lammens, Lieve

2018-05-20

The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation. Male Sprague-Dawley rats were dosed intracolonically via the rectum, using sodium caprate or ibuprofen as tool compounds to alter barrier integrity. Several potentially translational biomarkers and probe molecules related to permeability, inflammation or tissue damage were evaluated, using various analytical platforms, including immunoassays, targeted metabolomics and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry. Several markers were identified that allow early in vivo detection of colonic barrier integrity changes, before histopathological evidence of tissue damage. The most promising permeability markers identified were plasma fluorescein isothiocyanate-dextran 4000 and a lactulose/mannitol/sucralose mixture in urine. These markers showed maximum increases over 100-fold or approximately 10-50-fold, respectively. Intracolonic administration of the above probe molecules outperformed oral administration and inflammatory or other biomarkers, such as α 2 -macroglobulin, calprotectin, cytokines, prostaglandins and a panel of metabolic molecules to identify early and subtle changes in barrier integrity. However, optimal timing of probe administration and sample collection is important for all markers evaluated. Inclusion of these probe molecules in preclinical toxicity studies might aid in risk assessment and the design of a clinical biomarker plan, as several of these markers have translational potential. Copyright © 2018 John

Kinetics of the histologic, serologic and symptomatic responses to gluten challenge in adults with coeliac disease

PubMed Central

Leffler, Daniel A.; Schuppan, Detlef; Pallav, Kumar; Najarian, Robert; Goldsmith, Jeffery D.; Hansen, Joshua; Kabbani, Toufic; Dennis, Melinda; Kelly, Ciarán P.

2012-01-01

Objective Coeliac disease is defined by gluten responsiveness, yet there are few data on gluten challenge (GC) in adults on a gluten free diet. Lack of data regarding the kinetics of responses to gluten is a limitation in clinical practice and research when GC is performed. Design 20 adults with biopsy-proven coeliac disease participated. The study included two run-in visits followed by a 14 day GC at a randomly assigned dose of 3 or 7.5 grams of gluten/day. Study visits occurred 3, 7, 14 and 28 days after starting GC. Duodenal biopsy was performed during the run-in and at days 3 and 14 of GC. Villous height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count/100 enterocytes were measured by two pathologists. Antibodies to tTG and DGP, lactulose to mannitol ratio (LAMA), and symptoms were assessed at each visit. Results Significant reduction in Vh:Cd (2.2 to 1.1, p < 0.001) and increase in IELs (32.6 to 51.8, p < 0.001) were seen from baseline to day 14. Antibody titers increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did not change significantly. Gastrointestinal symptoms increased significantly by day 3 and returned to baseline by day 28. No differences were seen between the two gluten doses. Conclusions 14 day GC at ≥3 grams of gluten/day induces histological and serological changes in the majority of adults with coeliac disease. These data permit accurate design of clinical trials and indicate that many individuals will meet coeliac diagnostic criteria after a two week GC. PMID:22619366

Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach.

PubMed

Soldi, Sara; Vasileiadis, Sotirios; Uggeri, Francesca; Campanale, Mariachiara; Morelli, Lorenzo; Fogli, Maria Vittoria; Calanni, Fiorella; Grimaldi, Maria; Gasbarrini, Antonio

2015-01-01

Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response.

Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach

PubMed Central

Soldi, Sara; Vasileiadis, Sotirios; Uggeri, Francesca; Campanale, Mariachiara; Morelli, Lorenzo; Fogli, Maria Vittoria; Calanni, Fiorella; Grimaldi, Maria; Gasbarrini, Antonio

2015-01-01

Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response. PMID:26673000

Peripheral ammonia and blood brain barrier structure and function after methamphetamine.

PubMed

Northrop, Nicole A; Halpin, Laura E; Yamamoto, Bryan K

2016-08-01

An effect of the widely abuse psychostimulant, methamphetamine (Meth), is blood-brain-barrier (BBB) disruption; however, the mechanism by which Meth causes BBB disruption remains unclear. Recently it has been shown that Meth produces liver damage and consequent increases in plasma ammonia. Ammonia can mediate oxidative stress and inflammation, both of which are known to cause BBB disruption. Therefore, the current studies examined the role of peripheral ammonia in Meth-induced disruption of BBB structure and function. A neurotoxic Meth regimen (10 mg/kg, ip, q 2 h, ×4) administered to rats increased plasma ammonia and active MMP-9 in the cortex 2 h after the last Meth injection, compared to saline treated rats. At 24 h after Meth treatment, decreased immunoreactivity of BBB structural proteins, occludin and claudin-5, and increased extravasation of 10,000 Da FITC-dextran were observed, as compared to saline controls. Pretreatment with lactulose (5.3 g/kg, po, q 12 h), a drug that remains in the lumen of the intestine and promotes ammonia excretion, prevented the Meth-induced increases in plasma ammonia. These results were paralleled by the prevention of decreases in BBB structural proteins, increases in extravasation of 10,000 Da FITC-dextran and increases in active MMP-9. The results indicate that Meth-induced increases in ammonia produce BBB disruption and suggest that MMP-9 activation mediates the BBB disruption. These findings identify a novel mechanism of Meth-induced BBB disruption that is mediated by plasma ammonia and are the first to identify a peripheral contribution to Meth-induced BBB disruption. Copyright © 2016 Elsevier Ltd. All rights reserved.

A New Look at Precipitants of Overt Hepatic Encephalopathy in Cirrhosis.

PubMed

Pantham, Ganesh; Post, Anthony; Venkat, Deepak; Einstadter, Douglas; Mullen, Kevin D

2017-08-01

Overt hepatic encephalopathy (HE) is a major cause of significant morbidity and mortality in patients with liver cirrhosis. We examined the frequency and profile of the precipitating factors resulting in hospitalizations for overt HE. We conducted both retrospective and prospective studies to identify clinical precipitants of overt HE in patients with cirrhosis. The retrospective study patients were hospitalized at a large urban safety-net hospital, and the prospective study included the patients admitted at a liver transplant center. There were a total of 149 patients with cirrhosis and overt HE (91 males, mean age 55.3 ± 8.6 years) in the retrospective group and 45 patients (27 males, mean age 58.3 ± 8.2 years) in the prospective group of the study. The average MELD score was 16 ± 6.8 in the retrospective group and 22.7 ± 7.2 in the prospective group. Dehydration (46-76%), acute kidney injury (32-76%), lactulose nonadherence (about 50%), constipation (about 40%), and infections (20-42%) were the most frequently identified precipitants for hospitalization in retrospective and prospective groups. Multiple precipitants were identified in 60 (40.3%) patients in the retrospective group and 34 (76%) patients in the prospective group. Multiple concurrent precipitating factors were identified in the majority of patients with overt HE requiring hospitalization. Dehydration due to various causes was the most common precipitant of overt HE, followed by acute kidney injury (AKI), constipation, and infections. Prevention of dehydration, AKI, and constipation by close outpatient monitoring may be an effective measure to prevent hospitalization for overt HE in patients with cirrhosis.

Association between intestinal permeability and faecal microbiota composition in Italian children with beta cell autoimmunity at risk for type 1 diabetes.

PubMed

Maffeis, Claudio; Martina, Alessia; Corradi, Massimiliano; Quarella, Sara; Nori, Nicole; Torriani, Sandra; Plebani, Mario; Contreas, Giovanna; Felis, Giovanna E

2016-10-01

Pancreatic organ-specific autoimmunity in subjects at risk for type 1 diabetes (T1D) is associated with increased intestinal permeability and an aberrant gut microbiota, but these factors have not yet been simultaneously investigated in the same subjects. Thus, the aim of this study was to assess both intestinal permeability and gut microbiota composition in an Italian sample of children at risk for T1D. Ten Italian children with beta cell autoimmunity at risk for T1D and 10 healthy children were involved in a case-control study. The lactulose/mannitol test was used to assess intestinal permeability. Analysis of microbiota composition was performed using polymerase chain reaction followed by denaturing gradient gel electrophoresis, based on the 16S rRNA gene. Intestinal permeability was significantly higher in children at risk for T1D than in healthy controls. Moreover, the gut microbiota of the former differed from that of the latter group: Three microorganisms were detected - Dialister invisus, Gemella sanguinis and Bifidobacterium longum - in association with the pre-pathologic state. The results of this study validated the hypothesis that increased intestinal permeability together with differences in microbiota composition are contemporaneously associated with the pre-pathological condition of T1D in a sample of Italian children. Further studies are necessary to confirm the microbial markers identified in this sample of children as well as to clarify the involvement of microbiota modifications in the mechanisms leading to increased permeability and the autoimmune mechanisms that promote diabetes onset. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease.

PubMed

Leffler, Daniel; Schuppan, Detlef; Pallav, Kumar; Najarian, Robert; Goldsmith, Jeffery D; Hansen, Joshua; Kabbani, Toufic; Dennis, Melinda; Kelly, Ciarán P

2013-07-01

Coeliac disease is defined by gluten responsiveness, yet there are few data on gluten challenge (GC) in adults on a gluten-free diet. Lack of data regarding the kinetics of responses to gluten is a limitation in clinical practice and research when GC is performed. 20 adults with biopsy-proven coeliac disease participated. The study included two run-in visits followed by a 14-day GC at a randomly assigned dose of 3 or 7.5 g of gluten/day. Study visits occurred 3, 7, 14 and 28 days after starting GC. Duodenal biopsy was performed during the run-in and at days 3 and 14 of GC. Villous height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count/100 enterocytes were measured by two pathologists. Antibodies to tissue transglutaminase and deamidated gliadin peptides, lactulose to mannitol ratio (LAMA) and symptoms were assessed at each visit. Significant reduction in Vh:Cd (2.2-1.1, p<0.001) and increase in IELs (32.6-51.8, p<0.001) were seen from baseline to day 14. Antibody titres increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did not change significantly. Gastrointestinal symptoms increased significantly by day 3 and returned to baseline by day 28. No differences were seen between the two gluten doses. 14 day GC at ≥ 3 g of gluten/day induces histological and serological changes in the majority of adults with coeliac disease. These data permit accurate design of clinical trials and indicate that many individuals will meet coeliac diagnostic criteria after a 2-week GC.

Ethanol Production by Selected Intestinal Microorganisms and Lactic Acid Bacteria Growing under Different Nutritional Conditions.

PubMed

Elshaghabee, Fouad M F; Bockelmann, Wilhelm; Meske, Diana; de Vrese, Michael; Walte, Hans-Georg; Schrezenmeir, Juergen; Heller, Knut J

2016-01-01

To gain some specific insight into the roles microorganisms might play in non-alcoholic fatty liver disease (NAFLD), some intestinal and lactic acid bacteria and one yeast (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) were characterized by high performance liquid chromatography for production of ethanol when grown on different carbohydrates: hexoses (glucose and fructose), pentoses (arabinose and ribose), disaccharides (lactose and lactulose), and inulin. Highest amounts of ethanol were produced by S. cerevisiae, L. fermentum, and W. confusa on glucose and by S. cerevisiae and W. confusa on fructose. Due to mannitol-dehydrogenase expressed in L. fermentum, ethanol production on fructose was significantly (P < 0.05) reduced. Pyruvate and citrate, two potential electron acceptors for regeneration of NAD(+)/NADP(+), drastically reduced ethanol production with acetate produced instead in L. fermentum grown on glucose and W. confusa grown on glucose and fructose, respectively. In fecal slurries prepared from feces of four overweight volunteers, ethanol was found to be produced upon addition of fructose. Addition of A. caccae, L. acidophilus, L. fermentum, as well as citrate and pyruvate, respectively, abolished ethanol production. However, addition of W. confusa resulted in significantly (P < 0.05) increased production of ethanol. These results indicate that microorganisms like W. confusa, a hetero-fermentative, mannitol-dehydrogenase negative lactic acid bacterium, may promote NAFLD through ethanol produced from sugar fermentation, while other intestinal bacteria and homo- and hetero-fermentative but mannitol-dehydrogenase positive lactic acid bacteria may not promote NAFLD. Also, our studies indicate that dietary factors interfering with gastrointestinal microbiota and microbial

Pathogenesis of tropical sprue: A pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake

PubMed Central

Ghoshal, Uday C.; Kumar, Sunil; Misra, Asha; Choudhuri, Gourdas

2013-01-01

Background & objectives: Small intestinal bacterial overgrowth (SIBO) due to ileal brake-induced hypomotility may cause tropical sprue (TS). We evaluated effect of infusion of fat or placebo in duodenum randomly in patients with TS and healthy controls on antroduodenal manometry (ADM) and mediators of ileal brake, and duodenocaecal transit time (DCTT). Methods: ADM and DCTT (lactulose hydrogen breath test, HBT) were evaluated with placebo and fat in eight controls and 13 patients with TS (diagnostic criteria: tests showing malabsorption of two unrelated substances, abnormal duodenal histology, absence of other causes, response to antibiotics and folate). Results: Patients with TS (6 had SIBO by glucose HBT) were similar in age and gender with controls. After fat infusion, proximal gut motility index (MI) was reduced compared to fasting state in TS, and DCTT was longer in TS than controls (200 min, 120-380 vs. 130, 70-160, P=0.001), though comparable after placebo (70 min, 30-140 vs. 60, 40-90). TS patients had higher PYY and neurotensin than controls after fat infusion. DCTT after fat infusion correlated with plasma level of PYY in TS but not in controls. Post-fat PYY and neurotensin levels were higher in TS with lower BMI (<16 kg/m2) than those with higher BMI. Parameters of ileal brake (post-fat DCTT, PYY and neurotensin) were higher in patients with than without SIBO. Interpretation & conclusions: Fat infusion reduced proximal gut MI, increased DCTT, PYY, and neurotensin among patients with TS. Malabsorbed fat might cause exaggerated ileal brake reducing gut motility, promoting SIBO and bacterial colonization and malabsorption in TS. PMID:23481053

Identification of a Dehydrogenase Required for Lactose Metabolism in Caulobacter crescentus▿ †‡

PubMed Central

Arellano, Benjamin H.; Ortiz, Janett D.; Manzano, Janet; Chen, Joseph C.

2010-01-01

Caulobacter crescentus, which thrives in freshwater environments with low nutrient levels, serves as a model system for studying bacterial cell cycle regulation and organelle development. We examined its ability to utilize lactose (i) to gain insight into the metabolic capacities of oligotrophic bacteria and (ii) to obtain an additional genetic tool for studying this model organism, aiming to eliminate the basal enzymatic activity that hydrolyzes the chromogenic substrate 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal). Using a previously isolated transposon mutant, we identified a gene, lacA, that is required for growth on lactose as the sole carbon source and for turning colonies blue in the presence of X-gal. LacA, which contains a glucose-methanol-choline (GMC) oxidoreductase domain, has homology to the flavin subunit of Pectobacterium cypripedii's gluconate dehydrogenase. Sequence comparisons indicated that two genes near lacA, lacB and lacC, encode the other subunits of the membrane-bound dehydrogenase. In addition to lactose, all three lac genes are involved in the catabolism of three other β-galactosides (lactulose, lactitol, and methyl-β-d-galactoside) and two glucosides (salicin and trehalose). Dehydrogenase assays confirmed that the lac gene products oxidize lactose, salicin, and trehalose. This enzymatic activity is inducible, and increased lac expression in the presence of lactose and salicin likely contributes to the induction. Expression of lacA also depends on the presence of the lac genes, implying that the dehydrogenase participates in induction. The involvement of a dehydrogenase suggests that degradation of lactose and other sugars in C. crescentus may resemble a proposed pathway in Agrobacterium tumefaciens. PMID:20190087

Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients.

PubMed

Peng, Xi; Yan, Hong; You, Zhongyi; Wang, Pei; Wang, Shiliang

2004-03-01

Glutamine is an important energy source in intestinal mucosa, the small intestine is the major organ of glutamine uptake and metabolism and plays an important role in the maintenance of whole body glutamine homeostasis. The purpose of this clinical study is to observe the protection effects of enteral supplement with glutamine granules on intestinal mucosal barrier function in severe burned patients. Forty-eight severe burn patients (total burn surface area 30-75%, full thickness burn area 20-85%) were randomly divided into two groups: burn control group (B group, 23 patients) and glutamine treated group (Gln group, 25 patients). Glutamine granules 0.5 g/kg were supplied orally for 14 days in Gln group, and the same dosage of placebo were given for 14 days in B group. The plasma level of glutamine, endotoxin and the activity of diamine oxidase (DAO), as well as intestinal mucosal permeability were determined. The results showed that the levels of plasma endotoxin, activity and urinary lactulose and mannitol (L/M) ratio in all patients were significant higher than that of normal control. After taking glutamine granules for 14 days, plasma glutamine concentration was significantly higher in Gln group than that in B group (607.86+/-147.25 microM/l versus 447.63 +/- 132.28 microM/l, P < 0.01). On the other hand, the levels of plasma DAO activity and urinary L/M ratio in Gln group were lower than those in B group. In addition, the wound healing was better and hospital stay days were reduced in the Gln group (46.59 +/- 12.98 days versus 55.68 +/- 17.36 days, P < 0.05). These results indicated that glutamine granules taken orally could abate the degree of intestine injury, lessen intestinal mucosal permeability, ameliorate wound healing and reduce hospital stay.

Sourdough Bread Made from Wheat and Nontoxic Flours and Started with Selected Lactobacilli Is Tolerated in Celiac Sprue Patients

PubMed Central

Di Cagno, Raffaella; De Angelis, Maria; Auricchio, Salvatore; Greco, Luigi; Clarke, Charmaine; De Vincenzi, Massimo; Giovannini, Claudio; D'Archivio, Massimo; Landolfo, Francesca; Parrilli, Giampaolo; Minervini, Fabio; Arendt, Elke; Gobbetti, Marco

2004-01-01

This work was aimed at producing a sourdough bread that is tolerated by celiac sprue (CS) patients. Selected sourdough lactobacilli had specialized peptidases capable of hydrolyzing Pro-rich peptides, including the 33-mer peptide, the most potent inducer of gut-derived human T-cell lines in CS patients. This epitope, the most important in CS, was hydrolyzed completely after treatment with cells and their cytoplasmic extracts (CE). A sourdough made from a mixture of wheat (30%) and nontoxic oat, millet, and buckwheat flours was started with lactobacilli. After 24 h of fermentation, wheat gliadins and low-molecular-mass, alcohol-soluble polypeptides were hydrolyzed almost totally. Proteins were extracted from sourdough and used to produce a peptic-tryptic digest for in vitro agglutination tests on K 562(S) subclone cells of human origin. The minimal agglutinating activity was ca. 250 times higher than that of doughs chemically acidified or started with baker's yeast. Two types of bread, containing ca. 2 g of gluten, were produced with baker's yeast or lactobacilli and CE and used for an in vivo double-blind acute challenge of CS patients. Thirteen of the 17 patients showed a marked alteration of intestinal permeability after ingestion of baker's yeast bread. When fed the sourdough bread, the same 13 patients had values for excreted rhamnose and lactulose that did not differ significantly from the baseline values. The other 4 of the 17 CS patients did not respond to gluten after ingesting the baker's yeast or sourdough bread. These results showed that a bread biotechnology that uses selected lactobacilli, nontoxic flours, and a long fermentation time is a novel tool for decreasing the level of gluten intolerance in humans. PMID:14766592

Intestinal fatty acid-binding protein and gut permeability responses to exercise.

PubMed

March, Daniel S; Marchbank, Tania; Playford, Raymond J; Jones, Arwel W; Thatcher, Rhys; Davison, Glen

2017-05-01

Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Two-way repeated measures ANOVA revealed an arm × time interaction for L/R and I-FABP (P < 0.001). Post hoc analyses showed urinary L/R increased post-exercise in Plac (273% of pre, P < 0.001) and Col (148% of pre, P < 0.001) with post-exercise values significantly lower with Col (P < 0.001). Plasma I-FABP increased post-exercise in Plac (191% of pre-exercise, P = 0.002) but not in the Col arm (107%, P = 0.862) with post-exercise values significantly lower with Col (P = 0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P = 0.044) but not visit two (P = 0.200) although overall plots/patterns do appear similar for each. These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute.

Randomized Clinical Trial of Preoperative Feeding to Evaluate Intestinal Barrier Function in Neonates Requiring Cardiac Surgery.

PubMed

Zyblewski, Sinai C; Nietert, Paul J; Graham, Eric M; Taylor, Sarah N; Atz, Andrew M; Wagner, Carol L

2015-07-01

To evaluate intestinal barrier function in neonates undergoing cardiac surgery using lactulose/mannitol (L/M) ratio measurements, and to determine correlations with early breast milk feeding. This was a single-center, prospective, randomized pilot study of 27 term-born neonates (≥ 37 weeks gestation) requiring cardiac surgery who were randomized to 1 of 2 preoperative feeding groups: nil per os (NPO) or trophic (10 mL/kg/day) breast milk feeds. At 3 time points (preoperative [preop], postoperative [postop] day 7, and postop day 14), subjects were administered an oral L/M solution, after which urine L/M ratios were measured using gas chromatography, with higher ratios indicative of increased intestinal permeability. Trends over time in the mean urine L/M ratios for each group were estimated using a general linear mixed model. There were no adverse events related to preoperative trophic feeding. In the NPO group (n = 13), the mean urine L/M ratio was 0.06 at preop, 0.12 at postop day 7, and 0.17 at postop day 14. In the trophic breast milk feeds group (n = 14), the mean urine L/M ratio was 0.09 at preop, 0.19 at postop day 7, and 0.15 at postop day 14. In both groups, L/M ratios were significantly higher at postop day 7 and postop day 14 compared with preop (P < .05). Neonates have increased intestinal permeability after cardiac surgery extending to at least postop day 14. This pilot study was not powered to detect differences in benefit or adverse events comparing the NPO and trophic breast milk feeds groups. Further studies to identify mechanisms of intestinal injury and therapeutic interventions are warranted. Registered with ClinicalTrials.gov: NCT01475357. Copyright © 2015 Elsevier Inc. All rights reserved.

The obestatin/ghrelin ratio and ghrelin genetics in adult celiac patients before and after a gluten-free diet, in irritable bowel syndrome patients and healthy individuals.

PubMed

Russo, Francesco; Chimienti, Guglielmina; Linsalata, Michele; Clemente, Caterina; Orlando, Antonella; Riezzo, Giuseppe

2017-02-01

Ghrelin levels and obestatin/ghrelin ratio have been proposed as activity markers in ulcerative colitis, but no data are available in celiac disease (CD) and irritable bowel syndrome (IBS). Our aims were as follows: (a) to assess obestatin and ghrelin concentrations in adult active CD patients, diarrhea-predominant IBS (IBS-d), and healthy controls (HC) in relation to intestinal permeability; (b) to evaluate the ghrelin-obestatin profile in CD patients after a 1-year gluten-free diet (GFD); and (c) to establish the impact of ghrelin genetics. The study included 31 CD patients, 28 IBS-d patients, and 19 HC. Intestinal permeability, assayed by high-performance liquid chromatography determination of urinary lactulose (La)/mannitol (Ma), and circulating concentrations of obestatin, ghrelin, and their ratio were evaluated at enrollment and after GFD. The ghrelin single nucleotide polymorphisms Arg51Gln (rs34911341), Leu72Met (rs696217), and Gln90Leu (rs4684677) were analyzed. Intestinal permeability was impaired in CD patients and ameliorated after GFD. Ghrelin was significantly (P=0.048) higher and the obestatin/ghrelin ratio was significantly (P=0.034) lower in CD patients compared with both IBS-d and HC, and GFD reduced the peptide levels, but without reaching the concentrations in HC. Significant differences (P<0.05) were found in the Leu72Met polymorphism among groups, with the reduction of the GT genotype and the T allele in both CD and IBS-d patients compared with HC. Intestinal permeability is altered in CD, but not in IBS-d patients, and ghrelin levels increase in CD patients as observed in other inflammatory conditions. Moreover, a role for ghrelin genetics is hypothesized in sustaining the many pathogenetic components of these different pathologies, but with a similar symptom profile.

Effects of dietary live yeast supplementation on growth performance, diarrhoea severity, intestinal permeability and immunological parameters of weaned piglets challenged with enterotoxigenic Escherichia coli K88.

PubMed

Che, Lianqiang; Xu, Qin; Wu, Cheng; Luo, Yuheng; Huang, Xiaobo; Zhang, Bo; Auclair, Eric; Kiros, Tadele; Fang, Zhengfeng; Lin, Yan; Xu, Shengyu; Feng, Bin; Li, Jian; Wu, De

2017-12-01

This study aimed to investigate the effects of dietary live yeast (LY) supplementation on growth, intestinal permeability and immunological parameters of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Piglets weaned at 21 d were allocated into three treatments with six pens and six piglets per pen, receiving the control diet (CON), diets supplemented with antibiotics plus zinc oxide (ANT-ZnO) and LY (Saccharomyces cerevisiae strain CNCM I-4407), respectively, for a period of 2 weeks. On day 8, thirty-six piglets were selected as control without ETEC (CON), CON-ETEC, ANT-ZnO-ETEC and LY-ETEC groups challenged with ETEC until day 10 for sample collections. Piglets fed ANT-ZnO diet had the highest average daily gain and average daily feed intake (P<0·05) during the 1st week, but ADG of piglets fed the ANT-ZnO diet was similar as piglets fed LY diet during the second week. Piglets with LY-ETEC or ANT-ZnO-ETEC had markedly lower diarrhoea score (P<0·05) than piglets with CON-ETEC during the 24 h after ETEC challenge. Relative to piglets with CON, the counts of E. coli, urinary ratio of lactulose to mannitol, plasma IL-6 concentration, mRNA abundances of innate immunity-related genes in ileum and mesenteric lymph node tissues were increased (P<0·05), whereas the villous height of jejunum and relative protein expression of ileum claudin-1 were decreased (P<0·05) in piglets with CON-ETEC; however, these parameters did not markedly change in piglets with LY-ETEC or ANT-ZnO-ETEC. In summary, dietary LY supplementation could alleviate the severity of diarrhoea in piglets with ETEC, which may be associated with the improved permeability, innate immunity and bacterial profile.

Effects of Supplementation of the Synbiotic Ecologic® 825/FOS P6 on Intestinal Barrier Function in Healthy Humans: A Randomized Controlled Trial.

PubMed

Wilms, E; Gerritsen, J; Smidt, H; Besseling-van der Vaart, I; Rijkers, G T; Garcia Fuentes, A R; Masclee, A A M; Troost, F J

2016-01-01

Probiotics, prebiotics and synbiotics have been suggested as dietary strategies to improve intestinal barrier function. This study aimed to assess the effect of two weeks synbiotic supplementation on intestinal permeability under basal and stressed conditions. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and gastrointestinal symptoms including defecation pattern. Twenty healthy adults completed a double-blind, controlled, randomized, parallel design study. Groups either received synbiotic (1.5 × 1010 CFU Ecologic® 825 + 10 g fructo-oligosaccharides (FOS P6) per day) or control supplements for two weeks. Intestinal segment specific permeability was assessed non-invasively by oral administration of multiple sugar probes and, subsequently, assessing the excretion of these probes in urine. This test was conducted at baseline and at the end of intervention, in the absence and in the presence of an indomethacin challenge. Indomethacin was applied to induce a compromised gut state. Plasma zonulin, cytokines and chemokines were measured at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were recorded at baseline and daily during intervention. Significantly more male subjects were in the synbiotic group compared to the control group (P = 0.025). Indomethacin significantly increased urinary lactulose/rhamnose ratio versus without indomethacin, both in the control group (P = 0.005) and in the synbiotic group (P = 0.017). Urinary sugar recoveries and ratios, plasma levels of zonulin, cytokines and chemokines, and gastrointestinal symptom scores were not significantly different after control or synbiotic intervention. Stool frequency within the synbiotic group was significantly increased during synbiotic intervention compared to baseline (P = 0.039) and higher compared to control intervention (P = 0.045). Two weeks Ecologic® 825/FOS P6 supplementation increased stool frequency

Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome.

PubMed

Acosta, Andrés; Camilleri, Michael; Shin, Andrea; Linker Nord, Sara; O'Neill, Jessica; Gray, Amber V; Lueke, Alan J; Donato, Leslie J; Burton, Duane D; Szarka, Lawrence A; Zinsmeister, Alan R; Golden, Pamela L; Fodor, Anthony

2016-05-26

Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients. In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose-mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate). There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment). In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation.

Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics

PubMed Central

Gorenz, Annika; Shaikh, Maliha; Desai, Vishal; Forsyth, Christopher; Fogg, Louis; Burgess, Helen J.; Keshavarzian, Ali

2015-01-01

Chronic heavy alcohol use is known to cause gut leakiness and alcoholic liver disease (ALD), but only 30% of heavy drinkers develop increased intestinal permeability and ALD. The hypothesis of this study was that disruption of circadian rhythms is a potential risk factor in actively drinking alcoholics for gut leakiness and endotoxemia. We studied 20 subjects with alcohol use disorder (AD) and 17 healthy controls (HC, 6 day workers, 11 night workers). Subjects wore a wrist actiwatch for 7 days and underwent a 24-h dim light phase assessment and urine collection for intestinal permeability. The AD group had significantly less total sleep time and increased fragmentation of sleep (P < 0.05). AD also had significantly lower plasma melatonin levels compared with the HC [mean area under the curve (AUC) 322.78 ± 228.21 vs. 568.75 ± 304.26 pg/ml, P = 0.03]. In the AD group, AUC of melatonin was inversely correlated with small bowel and colonic intestinal permeability (lactulose-to-mannitol ratio, r = −0.39, P = 0.03; urinary sucralose, r = −0.47, P = 0.01). Cosinor analysis of lipopolysaccharide-binding protein (marker of endotoxemia) and lipopolysaccharide every 4 h for 24 h in HC and AD subjects had a midline estimating statistic of rhythm of 5,026.15 ± 409.56 vs. 6,818.02 ± 628.78 ng/ml (P < 0.01) and 0.09 ± 0.03 vs. 0.15 ± 0.19 EU/ml (P < 0.05), respectively. We found plasma melatonin was significantly lower in the AD group, and lower melatonin levels correlated with increased intestinal permeability and a marker of endotoxemia. Our study suggests the suppression of melatonin in AD may promote gut leakiness and endotoxemia. PMID:25907689

Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers.

PubMed

Kato, Takayuki; Honda, Yasushi; Kurita, Yusuke; Iwasaki, Akito; Sato, Takamitsu; Kessoku, Takaomi; Uchiyama, Shiori; Ogawa, Yuji; Ohkubo, Hidenori; Higurashi, Takuma; Yamanaka, Takeharu; Usuda, Haruki; Wada, Koichiro; Nakajima, Atsushi

2017-01-01

The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called "leaky gut syndrome." As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. Healthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal trial is needed to confirm

Increased small intestinal permeability in ulcerative colitis: rather genetic than environmental and a risk factor for extensive disease?

PubMed

Büning, Carsten; Geissler, Nora; Prager, Matthias; Sturm, Andreas; Baumgart, Daniel C; Büttner, Janine; Bühner, Sabine; Haas, Verena; Lochs, Herbert

2012-10-01

A disturbed epithelial barrier could play a pivotal role in ulcerative colitis (UC). We performed a family-based study analyzing in vivo gastrointestinal permeability in patients with UC, their healthy relatives, spouses, and controls. In total, 89 patients with UC in remission, 35 first-degree relatives (UC-R), 24 nonrelated spouses (UC-NR), and 99 healthy controls (HC) were studied. Permeability was assessed by a sugar-drink test using sucrose (gastroduodenal permeability), lactulose/mannitol (intestinal permeability), and sucralose (colonic permeability). Data were correlated with clinical characteristics including medical treatment. Increased intestinal permeability was detected significantly more often in UC patients in remission (25/89, 28.1%) compared with HC (6/99, 6.1%; P < 0.001). Similar results were obtained in UC-R (7/35, 20.0%; P = 0.01 compared with HC) regardless of sharing the same household with the patients or not. No difference was found between UC-NR (3/24, 12.5%) and HC. Notably, in UC patients increased intestinal permeability was found in 12/28 patients (42.9%) with pancolitis, 7/30 (23.3%) patients with left-sided colitis, and in 2/19 (10.5%) patients with proctitis (P = 0.04). Gastroduodenal and colonic permeability were similar in all groups. Among patients on azathioprine, increased intestinal permeability was only seen in 1/18 (5.6%) patients. In contrast, in 24/70 (34.3%) patients without azathioprine, an increased intestinal permeability was found (P = 0.005). An increased intestinal but not colonic permeability was found in UC patients in clinical remission that could mark a new risk factor for extensive disease location. Similar findings in healthy relatives but not spouses suggest that this barrier defect is genetically determined. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial.

PubMed

de Azevedo, Rodrigo Palacio; Freitas, Flávio Geraldo Resende; Ferreira, Elaine Maria; Pontes de Azevedo, Luciano Cesar; Machado, Flávia Ribeiro

2015-09-16

Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14. We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7% versus 62.3 ± 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups. Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score. Clinical Trials.gov NCT01607060, registered 24 May 2012.

Medical nutrition therapy as a potential complementary treatment for psoriasis--five case reports.

PubMed

Brown, Amy C; Hairfield, Michelle; Richards, Douglas G; McMillin, David L; Mein, Eric A; Nelson, Carl D

2004-09-01

This research evaluated five case studies of patients with psoriasis following a dietary regimen. There is no cure for psoriasis and the multiple treatments currently available only attempt to reduce the severity of symptoms. Treatments range from topical applications, systemic therapies, and phototherapy; while some are effective, many are associated with significant adverse effects. There is a need for effective, affordable therapies with fewer side effects that address the causes of the disorder. Evaluation consisted of a study group of five patients diagnosed with chronic plaque psoriasis (two men and three women, average age 52 years; range 40-68 years) attending a 10-day, live-in program during which a physician assessed psoriasis symptoms and bowel permeability. Subjects were then instructed on continuing the therapy protocol at home for six months. The dietary protocol, based on Edgar Cayce readings, included a diet of fresh fruits and vegetables, small amounts of protein from fish and fowl, fiber supplements, olive oil, and avoidance of red meat, processed foods, and refined carbohydrates. Saffron tea and slippery elm bark water were consumed daily. The five psoriasis cases, ranging from mild to severe at the study onset, improved on all measured outcomes over a six-month period when measured by the Psoriasis Area and Severity Index (PASI) (average pre- and post-test scores were 18.2 and 8.7, respectively), the Psoriasis Severity Scale (PSS) (average pre- and post-test scores were 14.6 and 5.4, respectively), and the lactulose/mannitol test of intestinal permeability (average pre- and post-test scores were 0.066 to 0.026, respectively). These results suggest a dietary regimen based on Edgar Cayce's readings may be an effective medical nutrition therapy for the complementary treatment of psoriasis; however, further research is warranted to confirm these results.

Perioperative Synbiotic Treatment to Prevent Postoperative Infectious Complications in Biliary Cancer Surgery

PubMed Central

Sugawara, Gen; Nagino, Masato; Nishio, Hideki; Ebata, Tomoki; Takagi, Kenji; Asahara, Takashi; Nomoto, Koji; Nimura, Yuji

2006-01-01

Summary Background Data: Use of synbiotics has been reported to benefit human health, but clinical value in surgical patients remains unclear. Objective: To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function, immune responses, systemic inflammatory responses, microflora, and surgical outcome in patients undergoing high-risk hepatobiliary resection. Methods: Patients with biliary cancer involving the hepatic hilus (n = 101) were randomized before hepatectomy, into a group receiving postoperative enteral feeding with synbiotics (group A); or another receiving preoperative plus postoperative synbiotics (group B). Lactulose-mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, natural killer (NK) cell activity, interleukin-6 (IL-6), fecal microflora, and fecal organic acid concentrations were determined before and after hepatectomy. Postoperative infectious complications were recorded. Results: Of 101 patients, 81 completed the trial. Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups. Preoperatively in group B, NK activity, and lymphocyte counts increased, while IL-6 decreased significantly (P < 0.05). Postoperative serum IL-6, white blood cell counts, and C-reactive protein in group B were significantly lower than in group A (P < 0.05). During the preoperative period, numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B (P < 0.05). Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A (P < 0.05). Incidence of postoperative infectious complications was 30.0% (12 of 40) in group A and 12.1% (5 of 41) in group B (P < 0.05). Conclusions: Preoperative oral administration of synbiotics can enhance immune responses, attenuate systemic postoperative inflammatory responses, and improve intestinal microbial

The effect of different dosages of guar gum on gastric emptying and small intestinal transit of a consumed semisolid meal.

PubMed

van Nieuwenhoven, M A; Kovacs, E M; Brummer, R J; Westerterp-Plantenga, M S; Brouns, F

2001-02-01

There is no consensus about the effect of guar gum supplementation on gastrointestinal transit. It has been suggested that guar gum slows gastric emptying and intestinal transit, thus inducing an increased feeling of satiety. To investigate whether addition of guar gum to a semisolid meal affects gastrointestinal transit. Eight male subjects were randomly studied four times. They consumed a standard semisolid test meal containing either 0 g, 2.5 g, 3.5 g, or 4.5 g of guar gum. The test meals contained 1 mCi 99mTc-hepatate for scintigraphy and 5 g lactulose for the H2-breath test. Scintigraphic scanning was performed for at least two hours, and gastric half-emptying time (T1/2) was calculated. Breath samples were collected at 15 minute intervals and analyzed for H2-enrichment. The orocecal transit time (OCTT) was then determined. A parameter of intestinal transit (PIT) was obtained by subtracting the T1/2 from the OCTT. There were no significant differences (in minutes) between the different tests in both T1/2 (0 g, t = 88.2 +/- 11, 2.5 g, t = 83.3 +/- 11.9, 3.5 g, t = 83.3 +/- 13.6, 4.5 g, t = 72.4 +/- 7.2, p = 0.86) and PIT (0 g, t = 149.9 +/- 26.6, 2.5 g, t = 145.5 +/- 25.6, t = 3.5 g, t = 175.3 +/- 17.6, t = 4.5 g, t = 152.6 +/- 22.4, p = 0.52). Addition of guar gum to a semisolid meal up to a dosage of 4.5 g does not affect gastrointestinal transit. Other mechanisms than gastrointestinal motility are involved in a possible satiating effect of guar gum supplementation.

Breath tests sustainability in hospital settings: cost analysis and reimbursement in the Italian National Health System.

PubMed

Volpe, M; Scaldaferri, F; Ojetti, V; Poscia, A

2013-01-01

The high demand of Breath Tests (BT) in many gastroenterological conditions in time of limited resources for health care systems, generates increased interest in cost analysis from the point of view of the delivery of services to better understand how use the money to generate value. This study aims to measure the cost of C13 Urea and other most utilized breath tests in order to describe key aspects of costs and reimbursements looking at the economic sustainability for the hospital. A hospital based cost-analysis of the main breath tests commonly delivery in an ambulatory setting is performed. Mean salary for professional nurses and gastroenterologists, drugs/preparation used and disposable materials, purchase and depreciation of the instrument and the testing time was used to estimate the cost, while reimbursements are based on the 2013 Italian National Health System ambulatory pricelist. Variables that could influence the model are considered in the sensitivity analyses. The mean cost for C13--Urea, Lactulose and Lactose BT are, respectively, Euros 30,59; 45,20 and 30,29. National reimbursement often doesn't cover the cost of the analysis, especially considering the scenario with lower number of exam. On the contrary, in high performance scenario all the reimbursement could cover the cost, except for the C13 Urea BT that is high influenced by the drugs cost. However, consideration about the difference between Italian Regional Health System ambulatory pricelist are done. Our analysis shows that while national reimbursement rates cover the costs of H2 breath testing, they do not cover sufficiently C13 BT, particularly urea breath test. The real economic strength of these non invasive tests should be considered in the overall organization of inpatient and outpatient clinic, accounting for complete diagnostic pathway for each gastrointestinal disease.

Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children.

PubMed

Gabriele, Stefano; Sacco, Roberto; Altieri, Laura; Neri, Cristina; Urbani, Andrea; Bravaccio, Carmela; Riccio, Maria Pia; Iovene, Maria Rosaria; Bombace, Francesca; De Magistris, Laura; Persico, Antonio M

2016-07-01

The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol-producing bacteria present in the gut lumen. Elevated p-cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p-cresol concentration (P < 0.05). No association was found with presence of Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability (P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD child was found to carry C. difficile in the gut or to release toxin A/B in the feces. In conclusion, urinary p-cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2016, 9: 752-759. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

The Impact of Mild Heat Stress During Prolonged Running On Gastrointestinal Integrity, Gastrointestinal Symptoms, Systemic Endotoxin and Cytokine Profiles.

PubMed

Snipe, Rhiannon M J; Khoo, Anthony; Kitic, Cecilia M; Gibson, Peter R; Costa, Ricardo J S

2018-02-07

The study aimed to determine the effects of mild exertional heat stress on intestinal injury, permeability, gastrointestinal symptoms, and systemic endotoxin and cytokine responses. Ten endurance runners completed 2 h of running at 60% V̇O 2max in warm (WARM: 30°C) and temperate (TEMP: 22°C) ambient conditions. Rectal temperature (T re ) and gastrointestinal symptoms were recorded every 10 min during exercise. Blood samples were collected pre- and post-exercise, and during recovery to determine plasma intestinal fatty acid-binding protein (I-FABP) and cortisol concentrations, and systemic endotoxin and inflammatory cytokine profiles. Urinary lactulose:L-rhamnose ratio (L/R) was used to measure small intestine permeability. Compared with TEMP, WARM significantly increased T re from 50 min onwards (38.1±0.3°C vs. 38.4±0.5°C, respectively; p<0.01), gastrointestinal symptoms (p=0.017), post-exercise plasma cortisol (26% vs. 59%, respectively; p<0.001) and I-FABP (127% vs. 184%, respectively; p<0.001) concentrations. Circulatory anti-endotoxin antibodies increased post-exercise (p<0.001) on WARM (20%) and TEMP (28%). No differences were observed for plasma endotoxin concentration (6% vs. 5% increase, respectively) or small intestine permeability (L/R 0.026±0.010 and 0.025±0.015, respectively). Both pro- and anti-inflammatory cytokines increased post-exercise, with inflammatory response cytokines TNF-α (p=0.015) and IL-8 (p=0.044), and compensatory anti-inflammatory cytokines IL-10 (p=0.065), and IL-1ra higher on WARM than TEMP. Findings suggest that exposure to warm ambient conditions during prolonged submaximal running induces transient intestinal epithelial injury, increases gastrointestinal symptoms, and promotes greater perturbations to the systemic cytokine profile compared to running in temperate conditions. © Georg Thieme Verlag KG Stuttgart · New York.

FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial.

PubMed

McIntosh, Keith; Reed, David E; Schneider, Theresa; Dang, Frances; Keshteli, Ammar H; De Palma, Giada; Madsen, Karen; Bercik, Premysl; Vanner, Stephen

2017-07-01

To gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the microbiome of patients with IBS. We performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota composition was analysed by 16S rRNA gene profiling. Thirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3-week diet. The IBS-SSS was reduced in the low FODMAP diet group (p<0.001) but not the high FODMAP group. LBTs showed a minor decrease in H 2 production in the low FODMAP compared with the high FODMAP group. Metabolic profiling of urine showed groups of patients with IBS differed significantly after the diet (p<0.01), with three metabolites (histamine, p-hydroxybenzoic acid, azelaic acid) being primarily responsible for discrimination between the two groups. Histamine, a measure of immune activation, was reduced eightfold in the low FODMAP group (p<0.05). Low FODMAP diet increased Actinobacteria richness and diversity, and high FODMAP diet decreased the relative abundance of bacteria involved in gas consumption. IBS symptoms are linked to FODMAP content and associated with alterations in the metabolome. In subsets of patients, FODMAPs modulate histamine levels and the microbiota, both of which could alter symptoms. NCT01829932. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Intestinal Barrier Function and the Gut Microbiome Are Differentially Affected in Mice Fed a Western-Style Diet or Drinking Water Supplemented with Fructose.

PubMed

Volynets, Valentina; Louis, Sandrine; Pretz, Dominik; Lang, Lisa; Ostaff, Maureen J; Wehkamp, Jan; Bischoff, Stephan C

2017-05-01

Background: The consumption of a Western-style diet (WSD) and high fructose intake are risk factors for metabolic diseases. The underlying mechanisms are largely unclear. Objective: To unravel the mechanisms by which a WSD and fructose promote metabolic disease, we investigated their effects on the gut microbiome and barrier function. Methods: Adult female C57BL/6J mice were fed a sugar- and fat-rich WSD or control diet (CD) for 12 wk and given access to tap water or fructose-supplemented water. The microbiota was analyzed with the use of 16S rRNA gene sequencing. Barrier function was studied with the use of permeability tests, and endotoxin, mucus thickness, and gene expressions were measured. Results: The WSD increased body weight gain but not endotoxin translocation compared with the CD. In contrast, high fructose intake increased endotoxin translocation 2.6- and 3.8-fold in the groups fed the CD + fructose and WSD + fructose, respectively, compared with the CD group. The WSD + fructose treatment also induced a loss of mucus thickness in the colon (-46%) and reduced defensin expression in the ileum and colon. The lactulose:mannitol ratio in the WSD + fructose mice was 1.8-fold higher than in the CD mice. Microbiota analysis revealed that fructose, but not the WSD, increased the Firmicutes:Bacteroidetes ratio by 88% for CD + fructose and 63% for WSD + fructose compared with the CD group. Bifidobacterium abundance was greater in the WSD mice than in the CD mice (63-fold) and in the WSD + fructose mice than in the CD + fructose mice (330-fold). Conclusions: The consumption of a WSD or high fructose intake differentially affects gut permeability and the microbiome. Whether these differences are related to the distinct clinical outcomes, whereby the WSD primarily promotes weight gain and high fructose intake causes barrier dysfunction, needs to be investigated in future studies. © 2017 American Society for Nutrition.

Breath Methane Excretion Is not An Accurate Marker of Colonic Methane Production in Irritable Bowel Syndrome.

PubMed

Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Klersy, Catherine; Pagani, Elisabetta; Miceli, Emanuela; Corazza, Gino Roberto

2015-06-01

The role of colonic methane production in functional bowel disorders is still uncertain. In small samples of irritable bowel syndrome (IBS) patients, it was shown that methane breath excretion correlates with clinical presentation and delayed gastrointestinal transit time. The aim of this study was to evaluate the relationship between intestinal production and breath excretion of CH4 and to correlate CH4 production with the presence and the severity of symptoms, in a large cohort of IBS patients and in a group of healthy volunteers. A group of 103 IBS patients and a group of 28 healthy volunteers were enrolled. The presence and severity of symptoms and gastrointestinal transit were evaluated in all subjects, who underwent breath H2/CH4 measurement for 7 h after lactulose to identify breath excretors of these gases; H2 and CH4 were also measured in rectal samples to identify colonic producers. Cumulative H2 and CH4 excretion and production were evaluated by the area under the time-concentration curve calculation (AUC). In IBS patients, CH4 was detected in rectal samples in 48 patients (47%), but only 27 of them (26% of the 103 enrolled patients) excreted this gas with breath. In CH4 producers, the prevalence and severity of symptoms and gastrointestinal transit time were not significantly different with respect to non-producers. IBS subtypes were homogeneously represented in CH4 producers and in non-producers. Healthy volunteers, compared with IBS patients, showed a significantly lower prevalence of CH4 excretion, whereas no difference was found in the prevalence of colonic CH4 production; moreover, in healthy volunteers compared with IBS, CH4 breath excretion and CH4 production were not different in quantitative terms. Our data show that colonic CH4 production is not associated with clinical presentation in IBS patients and does not correlate with symptom severity or with gastrointestinal transit time. Clinical inferences based on breath CH4 excretion should

Is Moderate Red Wine Consumption Safe in Inactive Inflammatory Bowel Disease?

PubMed Central

Swanson, Garth R.; Tieu, Vanessa; Shaikh, Maliha; Forsyth, Chris; Keshavarzian, Ali

2011-01-01

Background Alcohol consumption is a potential trigger for inflammatory bowel disease (IBD) flare because of alcohol-induced oxidative stress and its deleterious effects on gut barrier function. Additionally, we have recently shown that alcohol consumption is associated with more symptoms in IBD. However, it is not known whether moderate daily alcohol consumption can modify IBD disease activity. To test what effects alcohol may have on patients with IBD, we evaluated the effect of moderate daily red wine for 1 week on two factors associated with recurrent IBD disease activity: intestinal permeability and stool calprotectin. Methods To assess the effects of moderate daily alcohol consumption on intestinal permeability and inflammation, we recruited 21 patients: 8 with inactive ulcerative colitis (UC), 6 with inactive Crohn's disease (CD), and 7 healthy controls. All participants with IBD completed a validated questionnaire on disease activity (Crohn's disease activity index or ulcerative colitis clinical activity index), to confirm they had inactive disease. All subjects then underwent a baseline assessment that included a blood draw, urine collection after sugar challenge, and stool collection. Subjects then consumed 1–3 glasses of red wine a day for 1 week (approx. 0.4 g EtOH/kg), and repeated the three measures. Results No subjects flared during the study. Moderate alcohol consumption did not significantly change either clinical disease activity scores or C-reactive protein. In contrast to healthy subjects, daily consumption of red wine significantly (1) decreased stool calprotectin in IBD subjects from baseline (p = 0.001) and (2) increased intestinal permeability as measured by urinary lactulose/mannitol excretion (marker of small bowel permeability) in CD (p = 0.028) or urinary sucralose secretion (marker of large bowel permeability) in UC (p = 0.012). Conclusions One week of moderate consumption of red wine in inactive IBD was associated with a significant

Investigation of auranofin-induced diarrhoea.

PubMed Central

Behrens, R; Devereaux, M; Hazleman, B; Szaz, K; Calvin, J; Neale, G

1986-01-01

Gastrointestinal function was assessed in six patients with rheumatoid arthritis who had developed diarrhoea on treatment with Auranofin. With the administration of Auranofin whole gut transit time decreased markedly (to 50% or less of control values) in five of six patients. The speed of passage of intestinal contents through the colon was certainly increased but attempts to assess transit through the upper gastrointestinal tract failed because the breath hydrogen method gave inconclusive results. There was no evidence of colitis and in all cases biopsy of the rectal mucosa appeared normal by light microscopy. In the five patients with rapid intestinal transit faecal weight increased more than two-fold (range +44 to +335%) although in only three cases were the changes sufficient to cause an increased frequency of bowel action. Overall the concentration of sodium in faecal water increased three-fold (mean values rose from 10.6 to 38.3 mmol/l). There were no significant changes in the concentrations of either potassium or chloride but bicarbonate was reduced. Faecal pH fell from a mean value of 7.5 (range 6.8-7.9) to a mean value of 6.4 (range 6.0-7.4). In the three patients who developed overt diarrhoea and in two others taking Auranofin the intestinal uptake of 51Cr-EDTA was increased on average three-fold and there was a similar change in the ratio of the absorption of lactulose/mannitol. The mean clearance of alpha-1-antitrypsin from the circulation into the gastrointestinal tract was doubled. These data indicate an increase in intestinal permeability. In contrast the absorption of vitamin B12 was unaffected and there was no significant change in the excretion of faecal fat although one patient developed mild steatorrhoea. Thus in a selected group of subjects with rheumatoid arthritis the administration of Auranofin caused diarrhoea in association with a reversible defect in intestinal permeability but without significant change in the absorption of nutrients

Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation

PubMed Central

Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M.; Wolf, Patricia G.; Gaskins, H. Rex; Bharucha, Adil E.

2015-01-01

Background & Aims In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Methods Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average of 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Results Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P<.05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P<.05) and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. Conclusions After adjusting for diet and

Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings.

PubMed

Hedin, Charlotte R; McCarthy, Neil E; Louis, Petra; Farquharson, Freda M; McCartney, Sara; Taylor, Kirstin; Prescott, Natalie J; Murrells, Trevor; Stagg, Andrew J; Whelan, Kevin; Lindsay, James O

2014-10-01

Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip. Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ(2)=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables. Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Acute hyperammonemic encephalopathy after fluoropyrimidine-based chemotherapy: A case series and review of the literature.

PubMed

Mitani, Seiichiro; Kadowaki, Shigenori; Komori, Azusa; Sugiyama, Keiji; Narita, Yukiya; Taniguchi, Hiroya; Ura, Takashi; Ando, Masashi; Sato, Yozo; Yamaura, Hidekazu; Inaba, Yoshitaka; Ishihara, Makoto; Tanaka, Tsutomu; Tajika, Masahiro; Muro, Kei

2017-06-01

Acute hyperammonemic encephalopathy induced by fluoropyrimidines (FPs) is a rare complication. Its pathophysiology remains unclear, especially given the currently used regimens, including intermediate-doses of 5-fluorouracil (5-FU) or oral FP agents. We aimed to characterize the clinical manifestations in cancer patients who developed hyperammonemic encephalopathy after receiving FP-based chemotherapy.We retrospectively reviewed 1786 patients with gastrointestinal or primary-unknown cancer who received FP-based regimens between 2007 and 2012. Eleven patients (0.6%) developed acute hyperammonemic encephalopathy. The incidence according to the administered anticancer drugs were as follows: 5-FU (8 of 1176, 0.7%), S-1 (1 of 679, 0.1%), capecitabine (2 of 225, 0.9%), and tegafur-uracil (UFT) (0 of 39, 0%). Ten patients (90.9%) had at least 1 aggravating factor, including infection, dehydration, constipation, renal dysfunction, and muscle loss. All the 10 patients met the definition of sarcopenia. Median time to the onset of hyperammonemic encephalopathy in the cycle was 3 days (range: 2-21). Three patients (27.3%) developed encephalopathy during the first cycle of the regimen and the remaining 8 patients during the second or more cycles. Seven patients (63.6%) had received at least 1 other FP-containing regimen before without episodes of encephalopathy.All patients recovered soon after immediate discontinuation of chemotherapy and supportive therapies, such as hydration, infusion of branched-chain amino acids, and oral lactulose intake, with a median time to recovery of 2 days (range: <1-7). Four patients (36.4%) received FP-based regimens after improvement of symptoms; 3 patients were successfully managed with dose reduction, and 1 patient, who had developed encephalopathy due to S-1 monotherapy, received modified FOLFOX-6 therapy without encephalopathy later.FP-associated acute hyperammonemic encephalopathy is extremely rare, but a possible event at any time and even

Gastrointestinal symptoms in patients with liver cirrhosis: associations with nutritional status and health-related quality of life.

PubMed

Kalaitzakis, Evangelos; Simrén, Magnus; Olsson, Rolf; Henfridsson, Pia; Hugosson, Irene; Bengtsson, Maria; Björnsson, Einar

2006-12-01

Gastrointestinal symptoms can lead to decreased food intake and thereby increased morbidity. There is a general lack of data on the prevalence of gastrointestinal symptoms and their potential association with malnutrition and health-related quality of life (QoL) in cirrhosis. Our aim was to prospectively evaluate gastrointestinal symptoms, malnutrition, and QoL in patients with cirrhosis. Two validated questionnaires were used to measure gastrointestinal symptoms (gastrointestinal symptom rating scale (GSRS)) and health-related QoL (SF-36) in 128 consecutive cirrhotics (mean age 57 years, Child-Pugh score 8.6, MELD score 13.2) at a tertiary referral center. The results were compared with those of controls from the general population. Nutritional status was assessed by anthropometry and estimation of recent weight change. Compared to controls, cirrhotic patients showed higher gastrointestinal symptom severity (total GSRS score: 1.53, 95% CI 1.50-1.55 versus 2.21, 95% CI 2.04-2.38) and profound reductions in the SF-36 physical (47.0 95% CI 45.0-49.0 versus 37.9, 95% CI 35.7-40.1) and mental component summary scores (51.0 95% CI 49.0-53.0 versus 39.2 95% CI 36.7-41.6). There were no significant differences in any GSRS domain between patients with and those without malnutrition. Multivariate analysis showed that gastrointestinal symptom severity was associated with the Child-Pugh score (beta = 0.10, r<0.05), daily lactulose use (beta = 0.65, p<0.005), and the presence of gastrointestinal comorbidities (beta = 0.51, p<0.05). Negative weight change (beta = -0.72, p<0.05) and the SF-36 physical (beta = -4.26, p<0.005) and mental (beta = -4.53, p<0.005) summaries were independently related to gastrointestinal symptom severity. Patients with cirrhosis show increased severity of gastrointestinal symptoms, which are associated with recent weight loss and impaired health-related QoL. The severity of gastrointestinal symptoms seems to be related to the severity of cirrhosis.

High-Temperature Short-Time Pasteurization System for Donor Milk in a Human Milk Bank Setting

PubMed Central

Escuder-Vieco, Diana; Espinosa-Martos, Irene; Rodríguez, Juan M.; Corzo, Nieves; Montilla, Antonia; Siegfried, Pablo; Pallás-Alonso, Carmen R.; Fernández, Leónides

2018-01-01

Donor milk is the best alternative for the feeding of preterm newborns when mother's own milk is unavailable. For safety reasons, it is usually pasteurized by the Holder method (62.5°C for 30 min). Holder pasteurization results in a microbiological safe product but impairs the activity of many biologically active compounds such as immunoglobulins, enzymes, cytokines, growth factors, hormones or oxidative stress markers. High-temperature short-time (HTST) pasteurization has been proposed as an alternative for a better preservation of some of the biological components of human milk although, at present, there is no equipment available to perform this treatment under the current conditions of a human milk bank. In this work, the specific needs of a human milk bank setting were considered to design an HTST equipment for the continuous and adaptable (time-temperature combination) processing of donor milk. Microbiological quality, activity of indicator enzymes and indices for thermal damage of milk were evaluated before and after HTST treatment of 14 batches of donor milk using different temperature and time combinations and compared to the results obtained after Holder pasteurization. The HTST system has accurate and simple operation, allows the pasteurization of variable amounts of donor milk and reduces processing time and labor force. HTST processing at 72°C for, at least, 10 s efficiently destroyed all vegetative forms of microorganisms present initially in raw donor milk although sporulated Bacillus sp. survived this treatment. Alkaline phosphatase was completely destroyed after HTST processing at 72 and 75°C, but γ-glutamil transpeptidase showed higher thermoresistance. Furosine concentrations in HTST-treated donor milk were lower than after Holder pasteurization and lactulose content for HTST-treated donor milk was below the detection limit of analytical method (10 mg/L). In conclusion, processing of donor milk at 72°C for at least 10 s in this HTST system

Modulation of gut barrier function in patients with obstructive jaundice using probiotic LP299v.

PubMed

Jones, Claire; Badger, Stephen A; Regan, Mark; Clements, Barry W; Diamond, Tom; Parks, Rowan W; Taylor, Mark A

2013-12-01

This study aimed to determine the effect of LP229v on intestinal permeability and tumour necrosis factor (TNF) p55 receptor concentrations in patients with obstructive jaundice undergoing biliary drainage. Patients undergoing biliary drainage were recruited and randomized into three groups to receive Lactobacillus plantarum 299v (LP299v), inactivated LP299v (placebo) or water. These were administered daily at noon until 7 days after biliary drainage. Intestinal permeability was measured using the lactulose/mannitol (L/M) dual sugar absorption test on admission, the day before biliary drainage and on days 1 and 7 after biliary drainage. Blood and urine were collected to determine the L/M ratio and the TNF p55 receptor levels at each time point. A total of 25 patients were recruited; 12 had choledocholithiasis and nine had a periampullary tumour. Open surgical biliary drainage was performed in nine patients, endoscopic retrograde cholangiopancreatography in 12 and percutaneous transhepatic cholangiography in two. Five patients received LP299v, five received placebo and seven, water. The median L/M ratio was 0.035 (0.018-0.065) at baseline. No difference existed between the groups on admission, before drainage and on day 7 after drainage (P=0.59, 0.175 and 0.61, respectively). The L/M ratio was lower in the LP299v group on day 1 after drainage [0.01 (0.01) vs. 0.18 (0.03-0.3) and 0.11 (0.07-0.14); P=0.37]. Although the TNF p55 receptor levels were lower on day 1 after drainage in the LP299v group (15.3 vs. 30.9 vs. 82.7 ng/ml; P=0.43), the concentration at the four time points was similar (P=0.24, 0.96, 0.43 and 0.68). Pretreatment with probiotic LP299v improves intestinal permeability after biliary drainage and attenuates the inflammatory response. However, a larger multicentre trial is required to determine the effect on clinical outcome.

High-Temperature Short-Time Pasteurization System for Donor Milk in a Human Milk Bank Setting.

PubMed

Escuder-Vieco, Diana; Espinosa-Martos, Irene; Rodríguez, Juan M; Corzo, Nieves; Montilla, Antonia; Siegfried, Pablo; Pallás-Alonso, Carmen R; Fernández, Leónides

2018-01-01

Donor milk is the best alternative for the feeding of preterm newborns when mother's own milk is unavailable. For safety reasons, it is usually pasteurized by the Holder method (62.5°C for 30 min). Holder pasteurization results in a microbiological safe product but impairs the activity of many biologically active compounds such as immunoglobulins, enzymes, cytokines, growth factors, hormones or oxidative stress markers. High-temperature short-time (HTST) pasteurization has been proposed as an alternative for a better preservation of some of the biological components of human milk although, at present, there is no equipment available to perform this treatment under the current conditions of a human milk bank. In this work, the specific needs of a human milk bank setting were considered to design an HTST equipment for the continuous and adaptable (time-temperature combination) processing of donor milk. Microbiological quality, activity of indicator enzymes and indices for thermal damage of milk were evaluated before and after HTST treatment of 14 batches of donor milk using different temperature and time combinations and compared to the results obtained after Holder pasteurization. The HTST system has accurate and simple operation, allows the pasteurization of variable amounts of donor milk and reduces processing time and labor force. HTST processing at 72°C for, at least, 10 s efficiently destroyed all vegetative forms of microorganisms present initially in raw donor milk although sporulated Bacillus sp. survived this treatment. Alkaline phosphatase was completely destroyed after HTST processing at 72 and 75°C, but γ-glutamil transpeptidase showed higher thermoresistance. Furosine concentrations in HTST-treated donor milk were lower than after Holder pasteurization and lactulose content for HTST-treated donor milk was below the detection limit of analytical method (10 mg/L). In conclusion, processing of donor milk at 72°C for at least 10 s in this HTST system

A randomized, controlled trial of diathermy hemorrhoidectomy vs. stapled hemorrhoidectomy in an intended day-care setting with longer-term follow-up.

PubMed

Cheetham, M J; Cohen, C R G; Kamm, M A; Phillips, R K S

2003-04-01

Hemorrhoidectomy is the most effective long-term treatment for hemorrhoids. Although it is possible to perform hemorrhoidectomy as a day case with a high degree of patient satisfaction, patients take an average of 14 days off work after surgery. Stapled hemorrhoidectomy is believed to be less painful than conventional hemorrhoidectomy and should allow an earlier return to work. The aim of this study was to compare both the immediate and the long-term results of stapled hemorrhoidectomy with diathermy hemorrhoidectomy in patients with prolapsing internal hemorrhoids in an intended day-care setting. Thirty-one patients were randomly assigned to undergo diathermy hemorrhoidectomy (n = 16) or stapled hemorrhoidectomy performed with a purpose-designed endoluminal stapling device, PPH01T (n = 15). All operations were planned as day or short-stay cases. All patients received lactulose, commenced preoperatively, together with postoperative topical glyceryl trinitrate and oral metronidazole. Patients were assessed by structured interview to assess their symptoms before and after surgery, with an intended follow-up of six months. All patients completed a 10-cm visual analog pain scale daily for the first ten days after surgery. The total pain score (sum of all pain scores) was significantly higher in the diathermy group (50 (range, 9.8-79.9) vs. 19.6 (range, 1.3-89.5), P = 0.03). Patients took a median of 14 (range, 3-21) days off work after diathermy hemorrhoidectomy compared with 10 (range, 3-38) days for the patients undergoing stapled hemorrhoidectomy (P = 0.15). At long-term follow-up, three patients (all in the stapled group) developed new symptoms of fecal urgency and anal pain, and three patients required further surgery to remove symptomatic external hemorrhoids after stapled hemorrhoidectomy. Although stapled hemorrhoidectomy is less painful in the short term, this does not lead to a significantly earlier return to work, and some patients develop new symptoms at

Effects of Supplementation of the Synbiotic Ecologic® 825/FOS P6 on Intestinal Barrier Function in Healthy Humans: A Randomized Controlled Trial

PubMed Central

Wilms, E.; Gerritsen, J.; Smidt, H.; Besseling-van der Vaart, I.; Rijkers, G. T.; Garcia Fuentes, A. R.; Masclee, A. A. M.; Troost, F. J.

2016-01-01

Background and Aims Probiotics, prebiotics and synbiotics have been suggested as dietary strategies to improve intestinal barrier function. This study aimed to assess the effect of two weeks synbiotic supplementation on intestinal permeability under basal and stressed conditions. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and gastrointestinal symptoms including defecation pattern. Design Twenty healthy adults completed a double-blind, controlled, randomized, parallel design study. Intervention Groups either received synbiotic (1.5 × 1010 CFU Ecologic® 825 + 10 g fructo-oligosaccharides (FOS P6) per day) or control supplements for two weeks. Outcomes Intestinal segment specific permeability was assessed non-invasively by oral administration of multiple sugar probes and, subsequently, assessing the excretion of these probes in urine. This test was conducted at baseline and at the end of intervention, in the absence and in the presence of an indomethacin challenge. Indomethacin was applied to induce a compromised gut state. Plasma zonulin, cytokines and chemokines were measured at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were recorded at baseline and daily during intervention. Results Significantly more male subjects were in the synbiotic group compared to the control group (P = 0.025). Indomethacin significantly increased urinary lactulose/rhamnose ratio versus without indomethacin, both in the control group (P = 0.005) and in the synbiotic group (P = 0.017). Urinary sugar recoveries and ratios, plasma levels of zonulin, cytokines and chemokines, and gastrointestinal symptom scores were not significantly different after control or synbiotic intervention. Stool frequency within the synbiotic group was significantly increased during synbiotic intervention compared to baseline (P = 0.039) and higher compared to control intervention (P = 0.045). Conclusion Two weeks

Clinical management of acute liver failure: Results of an international multi-center survey

PubMed Central

Rabinowich, Liane; Wendon, Julia; Bernal, William; Shibolet, Oren

2016-01-01

AIM To assess the practice of caring for acute liver failure (ALF) patients in varying geographic locations and medical centers. METHODS Members of the European Acute Liver Failure Consortium completed an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed, treating between 300 and 500 ALF cases and performing over 100 liver transplants (LT) for ALF annually. The questions pertained to details of the institution and their clinical activity, standards of care, referral and admission, ward- based care versus intensive care unit (ICU) as well as questions regarding liver transplantation - including criteria, limitations, and perceived performance. Clinical data was also collected from 13 centres over a 3 mo period. RESULTS The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted, treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers, particularly in relation to recognition of severity and care of the more critically ill. Centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamol-related ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals, lactulose, nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure (ICP). ICP monitoring was employed in 12 centers, with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT, with a 90% post transplant

[The Latin-American Consensus on Chronic Constipation].

PubMed

Schmulson Wasserman, Max; Francisconi, Carlos; Olden, Kevin; Aguilar Paíz, Luis; Bustos-Fernández, Luis; Cohen, Henry; Passos, Maria Carmo; González-Martínez, Marina Alejandra; Iade, Beatriz; Iantorno, Guido; Ledesma Ginatta, Carlos; López-Colombo, Aurelio; Pérez, Cesar Louis; Madrid-Silva, Ana María; Quilici, Flavio; Quintero Samudio, Isaac; Rodríguez Varón, Alberto; Suazo, Jorge; Valenzuela, Jorge; Zolezzi, Alberto

2008-02-01

The Latin-American Consensus on Chronic Constipation aimed to establish guidelines to improve the identification, diagnosis and treatment of this disorder in the region. Two coordinators and an honorary coordinator established the process and the topics to be discussed, based on a systematic review of the literature published in the previous 10 years, since 1995. Seventeen members participated with the support of their local gastroenterology societies. The members reviewed the different subjects based on the levels of evidence and grades of recommendation; the topics were then discussed in a plenary session. A written report was drafted and the coordinators prepared the final declarations to be submitted to a vote by all the members in October 2006. The consensus concluded that chronic constipation has an estimated prevalence of 5-21% in the region, with a female-to-male ratio of 3:1. Among individuals with constipation, 75% use some type of medication, with more than 50% using home remedies. A diagnosis based on Rome Criteria was recommended and diagnostic testing only in persons older than 50 years or with alarm symptoms. The use of barium enema as an initial investigation was recommended only in countries with a high prevalence of idiopathic megacolon or Chagas' disease. Recommendations on treatment included an increase in dietary fiber of up to 25-30 g/day (grade C). No evidence was found to recommend measures such as exercise, increased water intake, or frequent visits to the toilet. Fiber supplements such as Psyllium received a grade B and pharmacological treatments such as tegaserod and polyethylene glycol, both grade A. There was insufficient evidence to recommend lactulose, but the consensus did not disadvise its use when necessary. Complementary investigations such as colonic transit followed by anorectal manometry and defecography were only recommended to rule out colonic inertia and/or obstructive defecation in patients not responding to treatment

Methane production and small intestinal bacterial overgrowth in children living in a slum.

PubMed

Mello, Carolina Santos; Tahan, Soraia; Melli, Lígia Cristina F L; Rodrigues, Mirian Silva do Carmo; de Mello, Ricardo Martin Pereira; Scaletsky, Isabel Cristina Affonso; de Morais, Mauro Batista

2012-11-07

To analyze small intestinal bacterial overgrowth in school-aged children and the relationship between hydrogen and methane production in breath tests. This transversal study included 85 children residing in a slum and 43 children from a private school, all aged between 6 and 10 years, in Osasco, Brazil. For characterization of the groups, data regarding the socioeconomic status and basic housing sanitary conditions were collected. Anthropometric data was obtained in children from both groups. All children completed the hydrogen (H(2)) and methane (CH(4)) breath test in order to assess small intestinal bacterial overgrowth (SIBO). SIBO was diagnosed when there was an increase in H(2) ≥ 20 ppm or CH(4) ≥ 10 ppm with regard to the fasting value until 60 min after lactulose ingestion. Children from the slum group had worse living conditions and lower nutritional indices than children from the private school. SIBO was found in 30.9% (26/84) of the children from the slum group and in 2.4% (1/41) from the private school group (P = 0.0007). Greater hydrogen production in the small intestine was observed in children from the slum group when compared to children from the private school (P = 0.007). A higher concentration of hydrogen in the small intestine (P < 0.001) and in the colon (P < 0.001) was observed among the children from the slum group with SIBO when compared to children from the slum group without SIBO. Methane production was observed in 63.1% (53/84) of the children from the slum group and in 19.5% (8/41) of the children from the private school group (P < 0.0001). Methane production was observed in 38/58 (65.5%) of the children without SIBO and in 15/26 (57.7%) of the children with SIBO from the slum. Colonic production of hydrogen was lower in methane-producing children (P = 0.017). Children who live in inadequate environmental conditions are at risk of bacterial overgrowth and methane production. Hydrogen is a substrate for methane production in the colon.

Lubiprostone Accelerates Intestinal Transit and Alleviates Small Intestinal Bacterial Overgrowth in Patients With Chronic Constipation.

PubMed

Sarosiek, Irene; Bashashati, Mohammad; Alvarez, Alicia; Hall, Mark; Shankar, Nagasri; Gomez, Yvette; McCallum, Richard W; Sarosiek, Jerzy

2016-09-01

Lubiprostone is an effective treatment for chronic constipation (CC). The mechanism of action of lubiprostone is through increasing fluid secretion and lubrication of the intestinal lumen. The effects of lubiprostone on gastrointestinal transit and small intestinal bacterial overgrowth (SIBO) have not been adequately explored. The current study was designed to investigate whether lubiprostone (1) alters gastrointestinal transit and (2) affects SIBO in patients with constipation. A total of 29 female patients (mean age = 39 years; range: 19-64) with CC received 2 weeks of lubiprostone (24mcg b.i.d., P.O.). Stool consistency based on Bristol stool scale and the frequency of bowel movements (BMs) were recorded. Gastric emptying time, small bowel transit time, colon transit time (CTT), combined small and large bowel transit time (SLBTT) and whole gut transit time were measured using wireless motility capsule. The SIBO status was assessed by the lactulose breath test. Data were analyzed using Wilcoxon rank, Mann-Whitney U, Spearman׳s rank correlation and Chi-square tests. Lubiprostone significantly softened the stool and increased the frequency of BM from median of 2 to 4times per week. The CTT and SLBTT were significantly shorter in responders to lubiprostone (i.e., those with ≥ 2 times increase in the number of their weekly BM) compared with nonresponders. The higher frequency of BM after treatment was significantly correlated with the acceleration of CTT, SLBTT and whole gut transit time. In all, 17 out of 25 (68%) patients, who were tested for SIBO at baseline, were positive. In addition, 7 out of 17 (41%) SIBO-positive patients became SIBO-negative after lubiprostone treatment (P < 0.05). In CC, lubiprostone improves the frequency of BMs, softens the stool, accelerates intestinal transit and decreases accompanying SIBO. The improvement of SIBO could be explained by the cleansing effect of increased intestinal fluid and mucus combined with enhanced intestinal

Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers

PubMed Central

Honda, Yasushi; Kurita, Yusuke; Iwasaki, Akito; Sato, Takamitsu; Kessoku, Takaomi; Uchiyama, Shiori; Ogawa, Yuji; Ohkubo, Hidenori; Higurashi, Takuma; Yamanaka, Takeharu; Usuda, Haruki; Wada, Koichiro; Nakajima, Atsushi

2017-01-01

Background and aims The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called “leaky gut syndrome.” As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. Methods Healthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. Results The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, −0.022–−0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. Conclusions This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate �

Sluggish gallbladder emptying and gastrointestinal transit after intake of common alcoholic beverages.

PubMed

Kasicka-Jonderko, A; Jonderko, K; Gajek, E; Piekielniak, A; Zawislan, R

2014-02-01

To study the movement along the gut and the effect upon the gallbladder volume of alcoholic beverages taken in the interdigestive state. The study comprised three research blocks attended by 12 healthy subjects each. Within a given research block volunteers underwent three examination sessions held on separate days, being offered an alcoholic beverage, or an aqueous ethanol solution of an identical proof, or a corresponding volume of isotonic glucose solution; the order of administration of the drinks was randomized. The beverages tested were: beer (4.7% vol, 400 ml), red wine (13.7% vol, 200 ml), whisky (43.5% vol, 100 ml) within the "Beer", "Wine", and "Whisky" research block, respectively. Gastric myoelectrical activity was examined electrogastrographically, gastric emptying with ¹³C-sodium acetate breath test, orocaecal transit with lactulose H₂ breath test, gallbladder emptying with ultrasonography, breath ethanol with alcotest. The study showed that alcoholic beverages were emptied from the stomach significantly slower than isotonic glucose. Alcoholic beverages produced by fermentation only (beer, red wine) were emptied from the stomach more slowly than ethanol solutions of identical proof, while gastric evacuation of whisky (distillation product) and matching alcohol solution was similar. The slower gastric evacuation of alcoholic beverages and ethanol solutions could not be ascribed to a disorganization of the gastric myoelectrical activity. The orocaecal transit of beer and red wine did not differ from that of isotonic glucose, whereas the orocaecal transit of whisky and high proof ethanol was markedly prolonged. Red wine and whisky, and to a similar extent control ethanol solutions caused an inhibition and delay of gallbladder emptying. We concluded that alcoholic beverages taken on an empty stomach exert a suppressive effect upon the transport function of the digestive tract and gallbladder emptying. The extent of this action depends on the type of a

Dietary sorbitol and mannitol: food content and distinct absorption patterns between healthy individuals and patients with irritable bowel syndrome.

PubMed

Yao, C K; Tan, H-L; van Langenberg, D R; Barrett, J S; Rose, R; Liels, K; Gibson, P R; Muir, J G

2014-04-01

Sorbitol and mannitol are naturally-occurring polyol isomers. Although poor absorption and induction of gastrointestinal symptoms by sorbitol are known, the properties of mannitol are poorly described. We aimed to expand data on food composition of these polyols, and to compare their absorptive capacities and symptom induction in patients with irritable bowel syndrome (IBS) and healthy individuals. Food samples were analysed for sorbitol and mannitol content. The degree of absorption measured by breath hydrogen production and gastrointestinal symptoms (visual analogue scales) was evaluated in a randomised, double-blinded, placebo-controlled study in 21 healthy and 20 IBS subjects after challenges with 10 g of sorbitol, mannitol or glucose. Certain fruits and sugar-free gum contained sorbitol, whereas mannitol content was higher in certain vegetables. Similar proportions of patients with IBS (40%) and healthy subjects (33%) completely absorbed sorbitol, although more so with IBS absorbed mannitol (80% versus 43%; P = 0.02). Breath hydrogen production was similar in both groups after lactulose but was reduced in patients with IBS after both polyols. No difference in mean (SEM) hydrogen production was found in healthy controls after sorbitol [area-under-the-curve: 2766 (591) ppm 4 h(-1) ] or mannitol [2062 (468) ppm 4 h(-1) ] but, in patients with IBS, this was greater after sorbitol [1136 (204) ppm 4 h(-1) ] than mannitol [404 (154) ppm 4 h(-1) ; P = 0.002]. Overall gastrointestinal symptoms increased significantly after both polyols in patients with IBS only, although they were independent of malabsorption of either of the polyols. Increased and discordant absorption of mannitol and sorbitol occurs in patients with IBS compared to that in healthy controls. Polyols induced gastrointestinal symptoms in patients with IBS independently of their absorptive patterns, suggesting that the dietary restriction of polyols may be efficacious. © 2013 The

A Combined Intervention of Zinc, Multiple Micronutrients, and Albendazole Does Not Ameliorate Environmental Enteric Dysfunction or Stunting in Rural Malawian Children in a Double-Blind Randomized Controlled Trial.

PubMed

Wang, Alfred Z; Shulman, Robert J; Crocker, Audrey H; Thakwalakwa, Chrissie; Maleta, Kenneth M; Devaraj, Sridevi; Manary, Mark J; Trehan, Indi

2017-01-01

Environmental enteric dysfunction (EED) and linear growth stunting affect many rural agrarian children in the developing world and contribute to the persistently high rates of stunting that are observed worldwide. Effective interventions to consistently ameliorate EED are lacking. We tested whether a bundle of safe and affordable interventions would decrease EED and stunting over 12-24 wk in a cohort of rural Malawian children 12-35 mo old. This was a randomized, double-blind, placebo-controlled clinical trial in which the intervention group received a single dose of albendazole and 14 d of zinc at enrollment and after 20 wk. The intervention group also received a daily multiple micronutrient powder throughout the 24 wk of study. The primary outcomes were improvements in EED, as measured by the urinary lactulose-to-mannitol ratio (L:M ratio) from dual-sugar absorption testing, and linear growth. Urinary L:M ratios and anthropometric measurements were evaluated after 12 and 24 wk of intervention and compared with a placebo group that did not receive any of these interventions. A total of 254 children were enrolled at a mean age of 24 mo; 55% were female. Their mean weight-for-age z score was -1.5, and their mean length-for-age z score was -0.9. After 12 and 24 wk of study, increases in the L:M ratio did not differ between the intervention group (0.071 and 0.088 units, respectively) and the placebo group (0.073 and 0.080 units, respectively) (P = 0.87 and 0.19, respectively). Relative changes in length and weight also did not differ significantly between groups at any time point. The combined usage of albendazole, zinc, and a daily multiple micronutrient powder did not decrease EED or stunting in this population of agrarian children 12-35 mo old in rural Malawi. Alternative interventions to improve these diseases should be investigated. This trial was registered at clinicaltrials.gov as NCT02253095. © 2017 American Society for Nutrition.

Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation.

PubMed

Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M; Wolf, Patricia G; Gaskins, H Rex; Bharucha, Adil E

2016-02-01

In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average, 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P < .05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P < .05), and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. After adjusting for diet and colonic transit, the profile of the microbiota in

Influence of Three Contrasting Detrital Carbon Sources on Planktonic Bacterial Metabolism in a Mesotrophic Lake.

PubMed

Wehr; Petersen; Findlay

1999-01-01

Abstract Lakes receive organic carbon from a diversity of sources which vary in their contribution to planktonic microbial food webs. We conducted a mesocosm study to test the effects of three different detrital carbon sources (algae, aquatic macrophytes, terrestrial leaves) on several measures of microbial metabolism in a small meso-eutrophic lake (DOC approximately 5 mg/L). Small DOC additions (DeltaC < 1 mg/L) affected bacterial numbers, growth, and pathways of carbon acquisition. Macrophyte and leaf detritus significantly increased TDP and color, but bacterial densities initially (+12 h) were unaffected. After 168 h, densities in systems amended with terrestrial detritus were 60% less than in controls, while production rates in mesocosms with macrophyte detritus were 4-fold greater. Detritus treatments resulted in greater per-cell production rates either through stable cell numbers and greater growth rates (macrophyte-C) or lower densities with stable production rates (terrestrial-C). After only 12 h, rates of leucine aminopeptidase (LAPase) activity were 2.5x greater in macrophyte-C systems than in controls, but LAPase and beta-N-acetylglucosamindase activities in systems amended with terrestrial-C were only 50% of rates in controls. After 168 h, beta-xylosidase rates were significantly greater in communities with terrestrial and phytoplankton detritus. Microbial utilization of >20% of 102 carbon sources tested were affected by at least one detritus addition. Macrophyte-C had positive (6% of substrates) and negative (14%) effects on substrate use; terrestrial detritus had mainly positive effects. An ordination based on carbon-use profiles (+12 h) revealed a cluster of macrophyte-amended communities with greater use of psicose, lactulose, and succinamic acid; controls and algal-detritus systems were more effective in metabolizing two common sugars and cellobiose. After 168 h, communities receiving terrestrial detritus were most tightly clustered, exhibiting

No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial.

PubMed

Kuzma, Jessica N; Cromer, Gail; Hagman, Derek K; Breymeyer, Kara L; Roth, Christian L; Foster-Schubert, Karen E; Holte, Sarah E; Weigle, David S; Kratz, Mario

2016-08-01

Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation. We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). Excessive amounts of fructose, HFCS, and glucose from SSBs

No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial1

PubMed Central

Cromer, Gail; Breymeyer, Kara L; Roth, Christian L; Weigle, David S

2016-01-01

Background: Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. Objective: We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation. Design: We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. Results: Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). Conclusion: Excessive

Capacity for absorption of water-soluble secondary metabolites greater in birds than in rodents.

PubMed

Karasov, William H; Caviedes-Vidal, Enrique; Bakken, Bradley Hartman; Izhaki, Ido; Samuni-Blank, Michal; Arad, Zeev

2012-01-01

Plant secondary metabolites (SMs) are pervasive in animal foods and potentially influence feeding behavior, interspecies interactions, and the distribution and abundance of animals. Some of the major classes of naturally occurring SMs in plants include many water-soluble compounds in the molecular size range that could cross the intestinal epithelium via the paracellular space by diffusion or solvent drag. There are differences among species in paracellular permeability. Using Middle Eastern rodent and avian consumers of fruits containing SMs, we tested the hypothesis that avian species would have significantly higher paracellular permeability than rodent species. Permeability in intact animals was assessed using standard pharmacological methodology to measure absorption of two radiolabeled, inert, neutral water-soluble probes that do not interact with intestinal nutrient transporters, L-arabinose (M(r) = 150.1 Da) and lactulose (M(r) = 342.3 Da). We also measured absorption of labeled 3-O-methyl-D-glucose (3OMD-glucose; M(r) = 194.2 Da), which is a nonmetabolized analogue of D-glucose that is passively absorbed through the paracellular space but also transported across the enterocyte membranes. Most glucose was absorbed by all species, but arabinose fractional absorption (f) was nearly three times higher in birds (1.03±0.17, n = 15 in two species) compared to rodents (0.37±0.06, n = 10 in two species) (P<0.001). Surprisingly, the apparent rates of absorption in birds of arabinose exceeded those of 3OMD-glucose. Our findings are in agreement with previous work showing that the paracellular pathway is more prominent in birds relative to nonflying mammals, and suggests that birds may be challenged by greater absorption of water-soluble, dietary SMs. The increased expression of the paracellular pathway in birds hints at a tradeoff: the free energy birds gain by absorbing water-soluble nutrients passively may be offset by the metabolic demands

Systematic Review: FDA-Approved Prescription Medications for Adults With Constipation

PubMed Central

Lacy, Brian E.

2006-01-01

Constipation is a common, often chronic, gastrointestinal disorder that can negatively impact the lives of those it affects and can be difficult to treat satisfactorily. The objective of this systematic review is to identify and analyze the available published literature on US Food and Drug Administration–approved prescription therapies for adults with constipation (episodic and chronic) and to assess their place in therapy, based on the methodologic strength and results of identified clinical trials. Ovid MEDLINE, PubMed, and EMBASE databases were used to search the published literature. Studies were included if they were randomized and prospective, conducted in adults (age ≥18), published as full-length manuscripts in English, and compared the test agent with placebo or a comparator(s). Studies were excluded if they involved patients with constipation attributed to secondary causes. Because fully published manuscripts from phase III efficacy trials involving the recently approved medication lubiprostone were not available, a manual search was performed of abstracts from the two annual major gastroenterology meetings (American College of Gastroenterology and Digestive Disease Week) from the past 4 years. Data on study design; number, age, and sex of patients; duration of treatment period; primary efficacy variable; secondary efficacy variables; adverse events; and discontinuations because of adverse events were abstracted from eligible articles. Eligible studies were assessed using well-established recommendations and a preformatted standardized form. A scoring system, with scores ranging from 1 to 15, was used to individually and separately assess the methodologic quality of the studies. Results of this analysis indicate a general lack of methodologically high-quality clinical trials supporting the use of lactulose and PEG 3350 to treat patients with chronic constipation, but data support their use in acute, episodic constipation. Conversely, high

Determinants and Impact of Giardia Infection in the First 2 Years of Life in the MAL-ED Birth Cohort

PubMed Central

Bartelt, Luther A.; Platts-Mills, James A.; Seidman, Jessica C.; Samie, Amidou; Havt, Alexandre; Babji, Sudhir; Trigoso, Dixner Rengifo; Qureshi, Shahida; Shakoor, Sadia; Haque, Rashidul; Mduma, Estomih; Bajracharya, Samita; Gaffar, S. M. Abdul; Lima, Aldo A. M.; Kang, Gagandeep; Kosek, Margaret N.; Ahmed, Tahmeed; Svensen, Erling; Mason, Carl; Bhutta, Zulfiqar A.; Lang, Dennis R.; Gottlieb, Michael; Guerrant, Richard L.; Houpt, Eric R.; Bessong, Pascal O.

2017-01-01

Abstract Background. Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study. Methods. From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression. Results. The incidence of at least 1 Giardia detection varied according to site (range, 37.7%–96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28–0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56–0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56–0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a −0.29 (95% CI, −0.53 to −0.05) deficit in weight-for-age z score and −0.29 (95% CI, −0.64 to 0.07) deficit in length-for-age z score at 2 years. Conclusions. Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of

Laboratory tests for diagnosis of food allergy: advantages, disadvantages and future perspectives.

PubMed

Moneret-Vautrin, D A; Kanny, G; Frémont, S

2003-04-01

Numerous biological tests point to the diagnosis of food sensitization: detection of specific IgEs by Rast techniques, multi-detection assays, immunoblotting, screening of basophil activation (BAT or FAST), assays for leukotriene LTC4 release (CAST), measurement of plasma histamine, serum tryptase, serum ECP, urinary EDN, completed by mannitol-lactulose test evaluating intestinal permeability, assay of fecal IgEs, Rast for specific IgG4. Primary screening for anti-food IgEs by multi-detection assays seeks justification from insufficient clinical data and false positive tests are common in patients sensitized to pollens or latex, on account of in vitro cross reactivities (CR). Multiple CR explain positive Rast to vegetal food allergens in such patients. Biological tests should not be performed as the first line of diagnosis. In vivo sensitisation is assessed by positive prick-tests, demonstrating the bivalence of allergens, as well as the affinity of specific IgEs, two conditions necessary to bridge membrane bound specific IgEs, leading to the release of mediators. Prick-tests are closer to clinical symptoms than biological tests. However, the diagnosis of food allergy is based on standardised oral challenges. Exceptions are high levels of specific IgEs to egg (> 6 kUl/l), peanut (> 15 kUl/l), fish (> 20 kUl/l) and milk (> 32 kUl/l), reaching a 95% predictive positive value. Rast inhibition tests are useful to identify masked allergens in foods. Research developments will have impact on the development of new diagnostic tools: allergen mixes reinforcing a food extract by associated recombinant major allergens, multiple combination of recombinant allergens (chips) or tests with synthetic epitopes aimed a the prediction of recovery. Laboratory tests take place in the decision free for the diagnosis for the food allergy and the follow-up of the levels specific IgEs is a tool to assess outcome and contributes to predict recovery or persistent allergy. Up to now the

New biomarkers for increased intestinal permeability induced by dextran sodium sulphate and fasting in chickens.

PubMed

Gilani, S; Howarth, G S; Kitessa, S M; Tran, C D; Forder, R E A; Hughes, R J

2017-10-01

Increased intestinal permeability (IP) can lead to compromised health in chickens. As there is limited literature on in vivo biomarkers to assess increased IP in chickens, the objective of this study was to identify a reliable biomarker of IP using DSS ingestion and fasting models. Male Ross chickens (n = 48) were reared until day 14 on the floor pen in an animal care facility, randomized into the following groups: control, DSS and fasting (each with n = 16), and then placed in metabolism cages. DSS was administered in drinking water at 0.75% from days 16 to 21, while controls and fasted groups received water. All birds had free access to feed and water except the birds in the fasting group that were denied feed for 19.5 h on day 20. On day 21, all chickens were given two separate oral gavages comprising fluorescein isothiocyanate dextran (FITC-d, 2.2 mg in 1 ml/bird) at time zero and lactulose, mannitol and rhamnose (LMR) sugars (0.25 g L, 0.05 g M and 0.05 g R in 2 ml/bird) at 60 min. Whole blood was collected from the brachial vein in a syringe 90 min post-LMR sugar gavage. Serum FITC-d and plasma LMR sugar concentrations were measured by spectrophotometry and high-performance ion chromatography respectively. Plasma concentrations of intestinal fatty acid binding protein, diamine oxidase, tight junction protein (TJP), d-lactate and faecal α-antitrypsin inhibitor concentration were also analysed by ELISA. FITC-d increased significantly (p < 0.05) after fasting compared with control. L/M and L/R ratios for fasting and L/M ratio for DSS increased compared with control chickens (p < 0.05). TJP in plasma was significantly increased due to fasting but not DSS treatment, compared with controls. Other tests did not indicate changes in IP (p > 0.05). We concluded that FITC-d and LMR sugar tests can be used in chickens to assess changes in IP. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Methane production and small intestinal bacterial overgrowth in children living in a slum

PubMed Central

Mello, Carolina Santos; Tahan, Soraia; Melli, Lígia Cristina FL; Rodrigues, Mirian Silva do Carmo; de Mello, Ricardo Martin Pereira; Scaletsky, Isabel Cristina Affonso; de Morais, Mauro Batista

2012-01-01

AIM: To analyze small intestinal bacterial overgrowth in school-aged children and the relationship between hydrogen and methane production in breath tests. METHODS: This transversal study included 85 children residing in a slum and 43 children from a private school, all aged between 6 and 10 years, in Osasco, Brazil. For characterization of the groups, data regarding the socioeconomic status and basic housing sanitary conditions were collected. Anthropometric data was obtained in children from both groups. All children completed the hydrogen (H2) and methane (CH4) breath test in order to assess small intestinal bacterial overgrowth (SIBO). SIBO was diagnosed when there was an increase in H2 ≥ 20 ppm or CH4 ≥ 10 ppm with regard to the fasting value until 60 min after lactulose ingestion. RESULTS: Children from the slum group had worse living conditions and lower nutritional indices than children from the private school. SIBO was found in 30.9% (26/84) of the children from the slum group and in 2.4% (1/41) from the private school group (P = 0.0007). Greater hydrogen production in the small intestine was observed in children from the slum group when compared to children from the private school (P = 0.007). A higher concentration of hydrogen in the small intestine (P < 0.001) and in the colon (P < 0.001) was observed among the children from the slum group with SIBO when compared to children from the slum group without SIBO. Methane production was observed in 63.1% (53/84) of the children from the slum group and in 19.5% (8/41) of the children from the private school group (P < 0.0001). Methane production was observed in 38/58 (65.5%) of the children without SIBO and in 15/26 (57.7%) of the children with SIBO from the slum. Colonic production of hydrogen was lower in methane-producing children (P = 0.017). CONCLUSION: Children who live in inadequate environmental conditions are at risk of bacterial overgrowth and methane production. Hydrogen is a substrate for

A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer.

PubMed

Hawley, Philippa Helen; Byeon, Jai Jun

2008-05-01

Constipation is a common and distressing condition in patients with cancer, especially those taking opioid analgesics. Many institutions prevent and treat constipation with titrated laxatives, which is known as a bowel protocol. An effective and well-tolerated bowel protocol is a very important component of cancer care, and there is little evidence on which to base selection of the most appropriate agents. This study compares a protocol of the stimulant laxative sennosides alone with a protocol of sennosides plus the stool softener docusate, in hospitalized patients at an oncology center. The docusate-containing protocol had an initial docusate-only step for patients not taking opioids, and four to six 100-mg capsules of docusate sodium in addition to the sennosides for the rest of the protocol. Thirty patients received the sennosides-only (S) protocol and 30 the sennosides plus docusate (DS) protocol. The efficacy and adverse effects of the protocols were monitored for 5-12 days. The two protocols were used sequentially, creating two cohorts, one on each protocol. Eighty percent of patients were taking oral opioids and 72% were admitted for symptom control/supportive care. Over a total of 488 days of observation it was found that the S protocol produced more bowel movements than the DS protocol, and in the symptom control/supportive care patients this difference was statistically significant (p < 0.05). In the S group admitted for symptom control/supportive care 62.5% had a bowel movement more than 50% of days, as compared with 32% in those receiving the DS protocol. Fifty-seven percent of the DS group required additional interventions (lactulose, suppositories or enemas) compared to 40% in the S group. Cramps were reported equally by 3 (10%) patients in each group. Eight patients (27%) experienced diarrhea in the S group compared to 4 (13%) in the DS group. The addition of the initial docusate-only step and adding docusate 400-600 mg/d to the sennosides did not

Complementary feeding with cowpea reduces growth faltering in rural Malawian infants: a blind, randomized controlled clinical trial.

PubMed

Stephenson, Kevin B; Agapova, Sophia E; Divala, Oscar; Kaimila, Yankho; Maleta, Kenneth M; Thakwalakwa, Chrissie; Ordiz, M Isabel; Trehan, Indi; Manary, Mark J

2017-12-01

Background: Growth faltering is common in rural African children and is attributed to inadequate dietary intake and environmental enteric dysfunction (EED). Objective: We tested the hypothesis that complementary feeding with cowpea or common bean flour would reduce growth faltering and EED in 6-mo-old rural Malawians compared with the control group receiving a corn-soy blend. Design: A prospective, double-blind, randomized controlled clinical trial was conducted in which children received daily feeding for 6 mo (200 kcal/d when 6-9 mo old and 300 kcal/d when 10-12 mo old). The primary outcomes were change in length-for-age z score (LAZ) and improvements in EED, as measured by percentage of lactulose excretion (%L). %L <0.2% was considered normal. Anthropometric measurements and %L through urine were compared between each legume group and the control group with Student's t test. Results: Of the 355 infants enrolled, 291 infants completed the trial, and 288 were breastfed throughout the duration of the study. Cowpea and common bean added 4.6-5.2 g protein/d and 4-5 g indigestible carbohydrate/d to the diet. LAZ and weight-for-height z score were reduced in all 3 groups from 6 to 12 mo of age. The changes in LAZ [mean (95% CI)] for the cowpea, common bean, and control groups from 6 to 9 mo were -0.14 (-0.24, -0.04), -0.27 (-0.38, -0.16), and -0.27 (-0.35, -0.19), respectively. LAZ was reduced less in infants receiving cowpea than in those receiving control food from 6 to 9 mo ( P = 0.048). The absolute value of %L did not differ between the dietary groups at 9 mo of age (mean ± SD: 0.30 ± 0.43, 0.23 ± 0.21, and 0.26 ± 0.31 for cowpea, common bean, and control, respectively), nor did the change in %L from 6 to 9 mo. Conclusion: Addition of cowpea to complementary feeding in Malawian infants resulted in less linear growth faltering. This trial was registered at clinicaltrials.gov as NCT02472262. © 2017 American Society for Nutrition.

Herbal Therapy Is Equivalent to Rifaximin for the Treatment of Small Intestinal Bacterial Overgrowth

PubMed Central

Chedid, Victor; Dhalla, Sameer; Clarke, John O.; Roland, Bani Chander; Dunbar, Kerry B.; Koh, Joyce; Justino, Edmundo; Tomakin, Eric

2014-01-01

Objective: Patients with small intestine bacterial overgrowth (SIBO) have chronic intestinal and extraintestinal symptomatology which adversely affects their quality of life. Present treatment of SIBO is limited to oral antibiotics with variable success. A growing number of patients are interested in using complementary and alternative therapies for their gastrointestinal health. The objective was to determine the remission rate of SIBO using either the antibiotic rifaximin or herbals in a tertiary care referral gastroenterology practice. Design: One hundred and four patients who tested positive for newly diagnosed SIBO by lactulose breath testing (LBT) were offered either rifaximin 1200 mg daily vs herbal therapy for 4 weeks with repeat LBT post-treatment. Results: Three hundred ninety-six patients underwent LBT for suspected SIBO, of which 251 (63.4%) were positive 165 underwent treatment and 104 had a follow-up LBT. Of the 37 patients who received herbal therapy, 17 (46%) had a negative follow-up LBT compared to 23/67 (34%) of rifaximin users (P=.24). The odds ratio of having a negative LBT after taking herbal therapy as compared to rifaximin was 1.85 (CI=0.77-4.41, P=.17) once adjusted for age, gender, SIBO risk factors and IBS status. Fourteen of the 44 (31.8%) rifaximin non-responders were offered herbal rescue therapy, with 8 of the 14 (57.1%) having a negative LBT after completing the rescue herbal therapy, while 10 non-responders were offered triple antibiotics with 6 responding (60%, P=.89). Adverse effects were reported among the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2 cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea was reported in the herbal therapy arm, which did not reach statistical significance (P=.22). Conclusion: SIBO is widely prevalent in a tertiary referral gastroenterology practice. Herbal therapies are at least as effective as rifaximin for resolution of SIBO by LBT. Herbals

Effect of glutamine-enriched nutritional support on intestinal mucosal barrier function, MMP-2, MMP-9 and immune function in patients with advanced gastric cancer during perioperative chemotherapy.

PubMed

Wang, Juan; Li, Yanfen; Qi, Yuanling

2017-09-01

We studied the effects of glutamine-enriched nutritional support on intestinal mucosal barrier, matrix metalloproteinase (MMP)-2, MMP-9 and immune function during perioperative chemotherapy in patients with advanced gastric cancer. The study was conducted on 94 patients with advanced gastric cancer admitted from April 2015 to March 2016. They were randomly divided into observation and control groups, n=47. Control group was given basic nutritional support whereas glutamine-enriched nutritional support was given to patients in observation group. High-performance liquid chromatography was used to measure lactulose and mannitol ratio in urine (L/M) and ELISA was used to measure D-lactate levels before chemotherapy and in the 1st, 2nd and 3rd cycle of chemotherapy. Immunoglobulin level was detected by immune turbidimetry assay, T lymphocyte subsets were determined by flow cytometry after 3 cycles of chemotherapy, MMP-2 and MMP-9 of patients were compared between the two groups. The serious adverse reactions incidence (grade and IV) of patients were observed. To evaluate the life quality of patients, QLQ-C30 was used after 6 months. The levels of L/M and D-lactate in both groups after the first cycle of chemotherapy were significantly higher than that before chemotherapy; they began to decline after the second or third cycle, but were still significantly higher than the levels before chemotherapy (p<0.05). On comparison, between the two groups after 1st, 2nd, 3rd cycle after chemotherapy, L/M and D-lactate levels of patients in the observation group were significantly lower than in the control group (p<0.05). Incidence of serious adverse reactions (grades III and IV) in observation group was significantly lower than control group (p<0.05). At follow-up of 6 months, living quality scores of patients in observation group were significantly higher than control group (p<0.05). Glutamine-enriched nutritional support can effectively protect the intestinal mucosal barrier

Pediatricians lack knowledge for the diagnosis and management of functional constipation in children over 6 mo of age

PubMed Central

Widodo, Ariani; Hegar, Badriul; Vandenplas, Yvan

2018-01-01

AIM To assess the knowledge of general pediatricians througout Indonesia about the diagnosis and treatment of childhood constipation. METHODS A comprehensive questionnaire was distributed to general pediatricians from several teaching hospitals and government hospitals all over Indonesia. RESULTS Data were obtained from 100 pediatricians, with a mean of 78.34 ± 18.00 mo clinical practice, from 20 cities throughout Indonesia. Suspicion of constipation in a child over 6 mo of age arises when the child presents with a decreased frequency of bowel movements (according to 87% of participants) with a mean of one bowel movement per 3.59 ± 1.0 d, hard stools (83%), blood in the stools (36%), fecal incontinence (33%), and/or difficulty in defecating (47%). Only 26 pediatricians prescribe pharmacologic treatment as first therapeutic approach, while the vast majority prefers nonpharmacologic treatment, mostly (according to 68%) The preferred nonpharmacologic treatment are high-fiber diet (96%), increased fluid intake (90%), toilet training (74%), and abdominal massage (49%). Duration of non-pharmacological treatment was limited to 1 to 2 wk. Seventy percent of the pediatricians recommending toilet training could only mention some elements of the technique, and only 15% was able to explain it fully and correctly. Lactulose is the most frequent pharmacologic intervention used (87% of the participants), and rectal treatment with sodium citrate, sodium lauryl sulfo acetate, and sorbitol is the most frequent rectal treatment (85%). Only 51% will prescribe rectal treatment for fecal impaction. The majority of the pediatricians (69%) expect a positive response during the first week with a mean (± SD) of 4.1 (± 2.56) d. Most participants (86%) treat during one month or even less. And the majority (67%) stops treatment when the frequency and/or consistency of the stools have become normal, or if the patient had no longer complaints. CONCLUSION These data provide an insight on the

Herbal therapy is equivalent to rifaximin for the treatment of small intestinal bacterial overgrowth.

PubMed

Chedid, Victor; Dhalla, Sameer; Clarke, John O; Roland, Bani Chander; Dunbar, Kerry B; Koh, Joyce; Justino, Edmundo; Tomakin, Eric; Mullin, Gerard E

2014-05-01

Patients with small intestine bacterial overgrowth (SIBO) have chronic intestinal and extraintestinal symptomatology which adversely affects their quality of life. Present treatment of SIBO is limited to oral antibiotics with variable success. A growing number of patients are interested in using complementary and alternative therapies for their gastrointestinal health. The objective was to determine the remission rate of SIBO using either the antibiotic rifaximin or herbals in a tertiary care referral gastroenterology practice. One hundred and four patients who tested positive for newly diagnosed SIBO by lactulose breath testing (LBT) were offered either rifaximin 1200 mg daily vs herbal therapy for 4 weeks with repeat LBT post-treatment. Three hundred ninety-six patients underwent LBT for suspected SIBO, of which 251 (63.4%) were positive 165 underwent treatment and 104 had a follow-up LBT. Of the 37 patients who received herbal therapy, 17 (46%) had a negative follow-up LBT compared to 23/67 (34%) of rifaximin users (P=.24). The odds ratio of having a negative LBT after taking herbal therapy as compared to rifaximin was 1.85 (CI=0.77-4.41, P=.17) once adjusted for age, gender, SIBO risk factors and IBS status. Fourteen of the 44 (31.8%) rifaximin non-responders were offered herbal rescue therapy, with 8 of the 14 (57.1%) having a negative LBT after completing the rescue herbal therapy, while 10 non-responders were offered triple antibiotics with 6 responding (60%, P=.89). Adverse effects were reported among the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2 cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea was reported in the herbal therapy arm, which did not reach statistical significance (P=.22). SIBO is widely prevalent in a tertiary referral gastroenterology practice. Herbal therapies are at least as effective as rifaximin for resolution of SIBO by LBT. Herbals also appear to be as effective as triple

Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study.

PubMed

Hawrelak, Jason A; Myers, Stephen P

2010-10-01

The study objective was to assess the effects and tolerability of two novel natural medicine formulations in improving bowel habit and abdominal symptoms in patients with irritable bowel syndrome (IBS). The DA-IBS formula was designed to treat diarrhea-predominant and alternating bowel habit IBS, and the C-IBS formula was designed to treat constipation-predominant IBS. This was a two arm, open-label, uncontrolled pilot study. Subjects were recruited from the greater Lismore area (NSW, Australia) in 2001. The study included 31 patients who fulfilled the Rome II criteria for IBS. Twenty-one (21) patients were classified as suffering from diarrhea-predominant or alternating bowel habit IBS and 10 patients were classified with constipation-predominant IBS. The DA-IBS formula consisted of a mixture of dried, powdered bilberry fruit, slippery elm bark, agrimony aerial parts, and cinnamon quills. The C-IBS formula consisted of a mixture of dried powdered slippery elm bark, lactulose, oat bran, and licorice root. The aim of each formula was to normalize stool frequency and stool consistency. Ingestion of the DA-IBS formula was associated with a small, but significant increase in bowel movement frequency (p = 0.027). Subjects in the DA-IBS group also experienced reductions in straining (p = 0.004), abdominal pain (p = 0.006), bloating (p < 0.0001), flatulence (p = 0.0001), and global IBS symptoms (p = 0.002) during the treatment phase of the trial. Subjects in the C-IBS group experienced a 20% increase in bowel movement frequency (p = 0.016) and significant reductions in straining (p < 0.0001), abdominal pain (p = 0.032), bloating (p = 0.034), and global IBS symptom severity (p = 0.0005), as well as improvements in stool consistency (p < 0.0001). Both formulas were well-tolerated. The DA-IBS formula was not effective in improving bowel habit in individuals with diarrhea-predominant or alternating bowel habit IBS, although it did significantly improve a number of IBS

Pediatricians lack knowledge for the diagnosis and management of functional constipation in children over 6 mo of age.

PubMed

Widodo, Ariani; Hegar, Badriul; Vandenplas, Yvan

2018-02-08

To assess the knowledge of general pediatricians througout Indonesia about the diagnosis and treatment of childhood constipation. A comprehensive questionnaire was distributed to general pediatricians from several teaching hospitals and government hospitals all over Indonesia. Data were obtained from 100 pediatricians, with a mean of 78.34 ± 18.00 mo clinical practice, from 20 cities throughout Indonesia. Suspicion of constipation in a child over 6 mo of age arises when the child presents with a decreased frequency of bowel movements (according to 87% of participants) with a mean of one bowel movement per 3.59 ± 1.0 d, hard stools (83%), blood in the stools (36%), fecal incontinence (33%), and/or difficulty in defecating (47%). Only 26 pediatricians prescribe pharmacologic treatment as first therapeutic approach, while the vast majority prefers nonpharmacologic treatment, mostly (according to 68%) The preferred nonpharmacologic treatment are high-fiber diet (96%), increased fluid intake (90%), toilet training (74%), and abdominal massage (49%). Duration of non-pharmacological treatment was limited to 1 to 2 wk. Seventy percent of the pediatricians recommending toilet training could only mention some elements of the technique, and only 15% was able to explain it fully and correctly. Lactulose is the most frequent pharmacologic intervention used (87% of the participants), and rectal treatment with sodium citrate, sodium lauryl sulfo acetate, and sorbitol is the most frequent rectal treatment (85%). Only 51% will prescribe rectal treatment for fecal impaction. The majority of the pediatricians (69%) expect a positive response during the first week with a mean (± SD) of 4.1 (± 2.56) d. Most participants (86%) treat during one month or even less. And the majority (67%) stops treatment when the frequency and/or consistency of the stools have become normal, or if the patient had no longer complaints. These data provide an insight on the diagnosis and management of

Perioperative Alanyl-Glutamine-Supplemented Parenteral Nutrition in Chronic Radiation Enteritis Patients With Surgical Intestinal Obstruction: A Prospective, Randomized, Controlled Study.

PubMed

Yao, Danhua; Zheng, Lei; Wang, Jian; Guo, Mingxiao; Yin, Jianyi; Li, Yousheng

2016-04-01

A prospective, randomized, controlled study was performed to evaluate the effects of perioperative alanyl-glutamine-supplemented parenteral nutrition (PN) support on the immunologic function, intestinal permeability, and nutrition status of surgical patients with chronic radiation enteritis (CRE)-induced intestinal obstruction. Patients who received 0.4 g/kg/d alanyl-glutamine and isonitrogenous PN were assigned to an alanyl-glutamine-supplemented PN (Gln-PN) group and a control group, respectively. Serum levels of alanine aminotransferase and glutamine, body fat mass (FM), immunologic function, and intestinal permeability were measured before and after surgery. Serum glutamine levels of the Gln-PN group significantly exceeded that of the control group (P < .001; Gln-PN, baseline 460.7 ± 42.5 vs 523.3 ± 48.6 µmol/L on postoperative day 14 [POD14], P < .001; control, baseline 451.9 ± 44.0 vs 453.8 ± 42.3 µmol/L on POD14, P = .708). Lactulose/mannitol ratios of both groups decreased over time (Gln-PN, baseline 0.129 ± 0.0403 vs 0.024 ± 0.0107 on POD1 4; control, baseline 0.125 ± 0.0378 vs 0.044 ± 0.0126 on POD14, P < .001 in both groups). CD4/CD8-positive T-lymphocyte ratios significantly rose in both groups, with significant intergroup difference (P < .001; Gln-PN, baseline 1.36 ± 0.32 vs 1.82 ± 0.30 on POD14, P < .001; control, baseline 1.37 ± 0.25 vs 1.63 ± 0.31 on POD14, P < .001). In the Gln-PN group, FM increased from 3.68 ± 1.68 kg at baseline to 5.22 ± 1.42 kg on POD14 (P < .001). FM of control group increased from 3.84 ± 1.57 kg at baseline to 5.40 ± 1.54 kg on POD14 (P < .001). However, there were no significant intergroup differences (P = .614). Gln-PN significantly boosted the immune state and decreased the intestinal permeability of CRE patients. However, Gln-PN was not superior to standard PN in improving the nutrition state and intestinal motility of surgical patients with CRE-induced intestinal obstruction. © 2015 American Society

A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge

PubMed Central

Leffler, Daniel A; Kelly, C P; Abdallah, H Z; Colatrella, A M; Harris, L A; Leon, F; Arterburn, L A; Paterson, B M; Lan, Z H; Murray, J A

2012-01-01

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1–mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge–placebo arm compared with the placebo–placebo arm

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: new observations with potential therapy.

PubMed

Brusilow, Saul W; Cooper, Arthur J L

2011-11-01

Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure, is a contributing factor: the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Case report. Johns Hopkins Hospital. A 22-yr-old woman who, 36 hrs before admission, ingested 15 g acetaminophen was admitted to the Johns Hopkins Hospital. She was treated with N-acetylcysteine. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hrs after ingestion when she became confused, irritable, and agitated. She was intubated, ventilated, and placed on lactulose. Shortly thereafter, she was noncommunicative, unresponsive to painful stimuli, and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure was made. She improved very slowly until 180 hrs after ingestion when she moved all extremities. She woke up shortly thereafter. Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in acute liver failure, the patient's plasma ammonia peaked when she exhibited no obvious neurologic deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurologic status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high but began to normalize several hours after plasma ammonia had returned to normal. The patient only started to recover as her plasma glutamine began

Sodium Butyrate Attenuates Diarrhea in Weaned Piglets and Promotes Tight Junction Protein Expression in Colon in a GPR109A-Dependent Manner.

PubMed

Feng, Wenqian; Wu, Yancheng; Chen, Guangxin; Fu, Shoupeng; Li, Bai; Huang, Bingxu; Wang, Dali; Wang, Wei; Liu, Juxiong

2018-06-27

Butyric acid plays an important role in maintaining intestinal health. Butyric acid has received special attention as a short-chain fatty acid, but its role in protecting the intestinal barrier is poorly characterized. Butyric acid not only provides energy for epithelial cells but also acts as a histone deacetylase inhibitor; it is also a natural ligand for G protein-coupled receptor 109A (GPR109A). A GPR109A analog was expressed in Sus scrofa and mediated the anti-inflammatory effects of beta-hydroxybutyric acid. This study investigated the effects of butyrate on growth performance, diarrhea symptoms, and tight junction protein levels in 21-day-old weaned piglets. We also studied the mechanism by which butyric acid regulates intestinal permeability. Twenty-four piglets that had been weaned at an age of 21 days were divided randomly into 2 equal groups: basal diet group and sodium butyrate + basal diet group. Diarrhea rate, growth performance during 3 weeks of feeding on these diets were observed, the lactulose-mannitol ratio in urine were detected by High Performance Liquid Chromatography, the expression levels of tight junction proteins in the intestinal tract and related signaling molecules, such as GPR109A and Akt, in the colon were examined by quantitative real-time PCR or western blot analyses on day 21. Caco-2 cells were used as a colon cell model and cultured with or without sodium butyrate to assess the expression of tight junction proteins and the activation of related signaling molecules. GPR109A-short hairpin RNA (shRNA) and specific antagonists of Akt and ERK1/2 were used as signaling pathway inhibitors to elucidate the mechanism by which butyric acid regulates the expression of tight junction proteins and the colonic epithelial barrier. The sodium butyrate diet alleviated diarrhea symptoms and decreased intestinal permeability without affecting the growth of early weaned piglets. The expression levels of the tight junction proteins Claudin-3, Occludin

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571).

PubMed

Tabbers, Merit M; Chmielewska, Ania; Roseboom, Maaike G; Boudet, Claire; Perrin, Catherine; Szajewska, Hania; Benninga, Marc A

2009-03-18

Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30-50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week. It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3-16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing Bifidobacterium lactis DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5-10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as > or = 3 bowel movements per week and < or =1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency > or = 3 on the last week of product consumption. To demonstrate that the success

The effects of acute oral glutamine supplementation on exercise-induced gastrointestinal permeability and heat shock protein expression in peripheral blood mononuclear cells.

PubMed

Zuhl, Micah; Dokladny, Karol; Mermier, Christine; Schneider, Suzanne; Salgado, Roy; Moseley, Pope

2015-01-01

Chronic glutamine supplementation reduces exercise-induced intestinal permeability and inhibits the NF-κB pro-inflammatory pathway in human peripheral blood mononuclear cells. These effects were correlated with activation of HSP70. The purpose of this paper is to test if an acute dose of oral glutamine prior to exercise reduces intestinal permeability along with activation of the heat shock response leading to inhibition of pro-inflammatory markers. Physically active subjects (N = 7) completed baseline and exercise intestinal permeability tests, determined by the percent ratio of urinary lactulose (5 g) to rhamnose (2 g). Exercise included two 60-min treadmill runs at 70 % of VO2max at 30 °C after ingestion of glutamine (Gln) or placebo (Pla). Plasma levels of endotoxin and TNF-α, along with peripheral blood mononuclear cell (PBMC) protein expression of HSP70 and IκBα, were measured pre- and post-exercise and 2 and 4 h post-exercise. Permeability increased in the Pla trial compared to that at rest (0.06 ± 0.01 vs. 0.02 ± 0.018) and did not increase in the Gln trial. Plasma endotoxin was lower at the 4-h time point in the Gln vs. 4 h in the Pla (6.715 ± 0.046 pg/ml vs. 7.952 ± 1.11 pg/ml). TNF-α was lower 4 h post-exercise in the Gln vs. Pla (1.64 ± 0.09 pg/ml vs. 1.87 ± 0.12 pg/ml). PBMC expression of IkBα was higher 4 h post-exercise in the Gln vs. 4 h in the Pla (1.29 ± 0.43 vs. 0.8892 ± 0.040). HSP70 was higher pre-exercise and 2 h post-exercise in the Gln vs. Pla (1.35 ± 0.21 vs. 1.000 ± 0.000 and 1.65 ± 0.21 vs. 1.27 ± 0.40). Acute oral glutamine supplementation prevents an exercise-induced rise in intestinal permeability and suppresses NF-κB activation in peripheral blood mononuclear cells.

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571)

PubMed Central

Tabbers, Merit M; Chmielewska, Ania; Roseboom, Maaike G; Boudet, Claire; Perrin, Catherine; Szajewska, Hania; Benninga, Marc A

2009-01-01

Background Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30–50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing Bifidobacterium lactis strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week. Methods/design It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3–16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing Bifidobacterium lactis DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5–10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as ≥ 3 bowel movements per week and ≤1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency ≥ 3 on the last week of product consumption. To

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: New observations with potential therapy

PubMed Central

Brusilow, Saul W; Cooper, Arthur J.L.

2011-01-01

Objective Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure (ALF), is a contributing factor – the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Design Case report. Setting Johns Hopkins Hospital. Patient A 22-year old white female who, 36 hours prior to admission, ingested 15 grams of acetaminophen was admitted to the Johns Hopkins Hospital. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hours after ingestion when she became confused, irritable and agitated. Interventions She was intubated, ventilated and placed on lactulose. Shortly thereafter she was non-communicative, unresponsive to painful stimuli and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure (ICP) was made. She improved very slowly until 180 hours after ingestion when she moved all extremities. She woke up shortly thereafter. Measurements and main results Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in ALF the patient’s plasma ammonia peaked when she exhibited no obvious neurological deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurological status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high, but began to normalize several hours after plasma ammonia had returned to normal. The

Synthesis and characterization of lactose-based homopolymers, hydrophilic/hydrophobic copolymers, and hydrogels

NASA Astrophysics Data System (ADS)

Zhou, Wenjing

The focus of this dissertation is the synthesis and characterization of lactose-based functional polymers. Currently 60% of lactose, a by-product from the cheese industry, is being utilized and the remaining fraction represents a serious disposal problem because of the high biological oxygen demand. Therefore, further development of utilization of lactose is an important issue both for industry and environment. Herein, the syntheses of lactose-based polymers such glycopolymers, hydrophilic/hydrophobic copolymers, and hydrogels are reported. A brief review of lactose formation, physical properties, and production is presented in Chapter 1. Syntheses and applications of lactose derivatives such as lactitol, lactulose, lactaime, lactosylurea, lactosylamine, lactone, and barbituric derivative are documented. Previous work in lactose-based polymers include: (1) hydrogels from cross linking of LPEP, borate complexation of lactose-containing polymer, and copolymerization of lactose monomer with crosslinkers; (2) lactose-based polyurethane rigid foams and adhesives; and (3) lactose-containing glycopolymers are also included. Chapter 2 documents the synthesis of acrylamidolactamine and the free radical copolymerization of this monomer with N-isopropylacrylamide in the presence of BisA to make hydrogels. Swelling behavior of the hydrogels at different temperatures as well as DSC study of these hydrogels are also carried out to characterize the swelling transition and the organization of water in the copolymer hydrogels. In Chapter 3, novel monomer syntheses of N-lactosyl- N'-(4-vinylbenzyl)urea or N '-lactosyl-N,N-methyl(4-vinylbenzyl)urea are described. Polymerization of these new urea monomers using a redox initiator gave water-soluble homopolymers with molecular weights in the range of 1.9 x 103 to 5.3 x 106. Synthesis and polymerization of lactose-O-(p-vinylbenzyl)hydroxime are documented in Chapter 4. The resulting polymers had high molecular weight (106) and narrow

An Exploratory Investigation of Endotoxin Levels in Novice Long Distance Triathletes, and the Effects of a Multi-Strain Probiotic/Prebiotic, Antioxidant Intervention.

PubMed

Roberts, Justin D; Suckling, Craig A; Peedle, Georgia Y; Murphy, Joseph A; Dawkins, Tony G; Roberts, Michael G

2016-11-17

Gastrointestinal (GI) ischemia during exercise is associated with luminal permeability and increased systemic lipopolysaccharides (LPS). This study aimed to assess the impact of a multistrain pro/prebiotic/antioxidant intervention on endotoxin unit levels and GI permeability in recreational athletes. Thirty healthy participants (25 males, 5 females) were randomly assigned either a multistrain pro/prebiotic/antioxidant (LAB⁴ ANTI ; 30 billion CFU·day -1 containing 10 billion CFU·day -1 Lactobacillus acidophilus CUL-60 (NCIMB 30157), 10 billion CFU·day -1 Lactobacillus acidophillus CUL-21 (NCIMB 30156), 9.5 billion CFU·day -1 Bifidobacterium bifidum CUL-20 (NCIMB 30172) and 0.5 billion CFU·day -1 Bifidobacterium animalis subspecies lactis CUL-34 (NCIMB 30153)/55.8 mg·day -1 fructooligosaccharides/ 400 mg·day -1 α-lipoic acid, 600 mg·day -1 N -acetyl-carnitine); matched pro/prebiotic (LAB⁴) or placebo (PL) for 12 weeks preceding a long-distance triathlon. Plasma endotoxin units (via Limulus amebocyte lysate chromogenic quantification) and GI permeability (via 5 h urinary lactulose (L): mannitol (M) recovery) were assessed at baseline, pre-race and six days post-race. Endotoxin unit levels were not significantly different between groups at baseline (LAB⁴ ANTI : 8.20 ± 1.60 pg·mL -1 ; LAB⁴: 8.92 ± 1.20 pg·mL -1 ; PL: 9.72 ± 2.42 pg·mL -1 ). The use of a 12-week LAB⁴ ANTI intervention significantly reduced endotoxin units both pre-race (4.37 ± 0.51 pg·mL -1 ) and six days post-race (5.18 ± 0.57 pg·mL -1 ; p = 0.03, ηp² = 0.35), but only six days post-race with LAB⁴ (5.01 ± 0.28 pg·mL -1 ; p = 0.01, ηp² = 0.43). In contrast, endotoxin units remained unchanged with PL. L:M significantly increased from 0.01 ± 0.01 at baseline to 0.06 ± 0.01 with PL only ( p = 0.004, ηp² = 0.51). Mean race times (h:min:s) were not statistically different between groups despite faster times with both pro/prebiotoic groups (LAB⁴ ANTI : 13:17:07 ± 0

An Exploratory Investigation of Endotoxin Levels in Novice Long Distance Triathletes, and the Effects of a Multi-Strain Probiotic/Prebiotic, Antioxidant Intervention

PubMed Central

Roberts, Justin D.; Suckling, Craig A.; Peedle, Georgia Y.; Murphy, Joseph A.; Dawkins, Tony G.; Roberts, Michael G.

2016-01-01

Gastrointestinal (GI) ischemia during exercise is associated with luminal permeability and increased systemic lipopolysaccharides (LPS). This study aimed to assess the impact of a multistrain pro/prebiotic/antioxidant intervention on endotoxin unit levels and GI permeability in recreational athletes. Thirty healthy participants (25 males, 5 females) were randomly assigned either a multistrain pro/prebiotic/antioxidant (LAB4ANTI; 30 billion CFU·day−1 containing 10 billion CFU·day−1 Lactobacillus acidophilus CUL-60 (NCIMB 30157), 10 billion CFU·day−1 Lactobacillus acidophillus CUL-21 (NCIMB 30156), 9.5 billion CFU·day−1 Bifidobacterium bifidum CUL-20 (NCIMB 30172) and 0.5 billion CFU·day−1 Bifidobacterium animalis subspecies lactis CUL-34 (NCIMB 30153)/55.8 mg·day−1 fructooligosaccharides/ 400 mg·day−1 α-lipoic acid, 600 mg·day−1 N-acetyl-carnitine); matched pro/prebiotic (LAB4) or placebo (PL) for 12 weeks preceding a long-distance triathlon. Plasma endotoxin units (via Limulus amebocyte lysate chromogenic quantification) and GI permeability (via 5 h urinary lactulose (L): mannitol (M) recovery) were assessed at baseline, pre-race and six days post-race. Endotoxin unit levels were not significantly different between groups at baseline (LAB4ANTI: 8.20 ± 1.60 pg·mL−1; LAB4: 8.92 ± 1.20 pg·mL−1; PL: 9.72 ± 2.42 pg·mL−1). The use of a 12-week LAB4ANTI intervention significantly reduced endotoxin units both pre-race (4.37 ± 0.51 pg·mL−1) and six days post-race (5.18 ± 0.57 pg·mL−1; p = 0.03, ηp2 = 0.35), but only six days post-race with LAB4 (5.01 ± 0.28 pg·mL−1; p = 0.01, ηp2 = 0.43). In contrast, endotoxin units remained unchanged with PL. L:M significantly increased from 0.01 ± 0.01 at baseline to 0.06 ± 0.01 with PL only (p = 0.004, ηp2 = 0.51). Mean race times (h:min:s) were not statistically different between groups despite faster times with both pro/prebiotoic groups (LAB4ANTI: 13:17:07 ± 0:34:48; LAB4: 12

The effectiveness of selected feed and water additives for reducing Salmonella spp. of public health importance in broiler chickens: a systematic review, meta-analysis, and meta-regression approach.

PubMed

Totton, Sarah C; Farrar, Ashley M; Wilkins, Wendy; Bucher, Oliver; Waddell, Lisa A; Wilhelm, Barbara J; McEwen, Scott A; Rajić, Andrijana

2012-10-01

Eating inappropriately prepared poultry meat is a major cause of foodborne salmonellosis. Our objectives were to determine the efficacy of feed and water additives (other than competitive exclusion and antimicrobials) on reducing Salmonella prevalence or concentration in broiler chickens using systematic review-meta-analysis and to explore sources of heterogeneity found in the meta-analysis through meta-regression. Six electronic databases were searched (Current Contents (1999-2009), Agricola (1924-2009), MEDLINE (1860-2009), Scopus (1960-2009), Centre for Agricultural Bioscience (CAB) (1913-2009), and CAB Global Health (1971-2009)), five topic experts were contacted, and the bibliographies of review articles and a topic-relevant textbook were manually searched to identify all relevant research. Study inclusion criteria comprised: English-language primary research investigating the effects of feed and water additives on the Salmonella prevalence or concentration in broiler chickens. Data extraction and study methodological assessment were conducted by two reviewers independently using pretested forms. Seventy challenge studies (n=910 unique treatment-control comparisons), seven controlled studies (n=154), and one quasi-experiment (n=1) met the inclusion criteria. Compared to an assumed control group prevalence of 44 of 1000 broilers, random-effects meta-analysis indicated that the Salmonella cecal colonization in groups with prebiotics (fructooligosaccharide, lactose, whey, dried milk, lactulose, lactosucrose, sucrose, maltose, mannanoligosaccharide) added to feed or water was 15 out of 1000 broilers; with lactose added to feed or water it was 10 out of 1000 broilers; with experimental chlorate product (ECP) added to feed or water it was 21 out of 1000. For ECP the concentration of Salmonella in the ceca was decreased by 0.61 log(10)cfu/g in the treated group compared to the control group. Significant heterogeneity (Cochran's Q-statistic p≤0.10) was observed

Elevated methane levels in small intestinal bacterial overgrowth suggests delayed small bowel and colonic transit.

PubMed

Suri, Jaspreet; Kataria, Rahul; Malik, Zubair; Parkman, Henry P; Schey, Ron

2018-05-01

Limited research exists regarding the relationship between small intestinal bacterial overgrowth (SIBO), small bowel transit (SBT), and colonic transit (CT). Furthermore, symptom analysis is limited between the subtypes of SIBO: hydrogen producing (H-SIBO) and methane producing (M-SIBO). The primary aims of this study are to: compare the SBT and CT in patients with a positive lactulose breath test (LBT) to those with a normal study; compare the SBT and CT among patients with H-SIBO or M-SIBO; compare the severity of symptoms in patients with a positive LBT to those with a normal study; compare the severity of symptoms among patients with H-SIBO or M-SIBO.A retrospective review was performed for 89 patients who underwent a LBT and whole gut transit scintigraphy (WGTS) between 2014 and 2016. Seventy-eight patients were included. WGTS evaluated gastric emptying, SBT (normal ≥40% radiotracer bolus accumulated at the ileocecal valve at 6 hours), and CT (normal geometric center of colonic activity = 1.6-7.0 at 24 hours, 4.0-7.0 at 48 hours, 6.2-7.0 at 72 hours; elevated geometric center indicates increased transit). We also had patients complete a pretest symptom survey to evaluate nausea, bloating, constipation, diarrhea, belching, and flatulence.A total of 78 patients (69 females, 9 males, mean age of 48 years, mean BMI of 25.9) were evaluated. Forty-seven patients had a positive LBT (H-SIBO 66%, M-SIBO 34%). Comparison of SBT among patients with a positive LBT to normal LBT revealed no significant difference (62.1% vs 58.6%, P = .63). The mean accumulated radiotracer was higher for H-SIBO compared to M-SIBO (71.5% vs 44.1%; P < .05). For CT, all SIBO patients had no significant difference in geometric centers of colonic activity at 24, 48, and 72 hours when compared to the normal group. When subtyping, H-SIBO had significantly higher geometric centers compared to the M-SIBO group at 24 hours (4.4 vs 3.1, P < .001), 48 hours (5.2 vs 3

Medical management of chronic liver diseases (CLD) in children (part II): focus on the complications of CLD, and CLD that require special considerations.

PubMed

El-Shabrawi, Mortada H F; Kamal, Naglaa M

2011-12-01

Treatment of the causes of many chronic liver diseases (CLDs) may not be possible. In this case, complications must be anticipated, prevented or at least controlled by the best available therapeutic modalities. There are three main goals for the management of portal hypertension: (i) prevention of the first episode of variceal bleeding largely by non-selective β-adrenoceptor antagonists, which is not generally recommended in children; (ii) control of bleeding by using a stepwise approach from the least to most invasive strategies; (iii) and prevention of re-bleeding using bypass operations, with particular enthusiasm for the use of meso-Rex bypass in the pediatric population. Hepatic encephalopathy management also consists of three main aspects: (i) ruling out other causes of encephalopathy; (ii) identifying and treating precipitating factors; and (iii) starting empiric treatment with drugs such as lactulose, rifaximin, sodium benzoate, and flumazenil. Treatment of mild ascites and peripheral edema should begin with the restriction of sodium and water, followed by careful diuresis, then large-volume paracentesis associated with colloid volume expansion in severe cases. Empiric broad spectrum antimicrobial therapy should be used for the treatment of spontaneous bacterial peritonitis, bacterial and fungal sepsis, and cholangitis, after taking appropriate cultures, with appropriate changes in therapy after sensitivity testing. Empirical therapies continue to be the standard practice for pruritus; these consist of bile acid binding agents, phenobarbital (phenobarbitone), ursodeoxycholic acid, antihistamines, rifampin (rifampicin), and carbamazepine. Partial external biliary diversion can be used in refractory cases. Once hepatorenal syndrome is suspected, treatment should be initiated early in order to prevent the progression of renal failure; approaches consist of general supportive measures, management of concomitant complications, screening for sepsis, treatment

[Clinical features of irritable bowel syndrome with small intestinal bacterial overgrowth and a preliminary study of effectiveness of Rifaximin].

PubMed

Liu, Z J; Wei, H; Duan, L P; Zhu, S W; Zhang, L; Wang, K

2016-06-28

To investigate the prevalence and clinical features of small intestinal bacterial overgrowth (SIBO) in diarrhea-predominant irritable bowel syndrome (IBS-D) patients detected by hydrogen and methane in lactulose breath test (LBT), and to study the effects of rifaximin in IBS-D patients. Consecutive patients with IBS-D who met Rome Ⅲ criteria, and gender- and age-matched healthy volunteers were enrolled from March 2015 to January 2016 in Peking University Third Hospital. All the ISB-D patients underwent LBT to detect the prevalence of SIBO. The clinical and LBT features of IBS with SIBO (IBS-P group) and without SIBO (IBS-N group) were analyzed. The effects of rifaximin therapy (0.4 g, twice per day for 4 weeks) in IBS-D patients were evaluated by comparing changes in clinical features and LBT results after treatment. (1) Eighty-four IBS-D patients and 22 healthy controls were enrolled. The prevalence of SIBO in IBS-D patients was 41.67% (35/84), with 27 (77.14%) only hydrogen-positive, 5 (14.29%) methane-positive, and 3 (8.57%) both methane- and hydrogen-positive. (2) The body mass index (BMI) in the IBS-P group was lower than in the IBS-N group [(21.61±0.57) vs (23.44±0.54) kg/m(2,) P<0.05], the maximum stool frequency was also less than in the IBS-N group [(3.85±0.23) vs (4.88±0.35) times/day, P<0.05]. (3) No significant difference was found in oro-cecal transit time (OCTT) among IBS-P, IBS-N and healthy controls. The hydrogen concentration in small intestinal and colonic sections in breath of the IBS-P group was higher than that of both healthy controls and the IBS-N group, while methane concentration in small intestinal and colonic sections (160 min) was higher than that of the IBS-N group (all P<0.05). (4) There was no linear relationship between mean hydrogen and methane concentrations in LBT among the IBS-P, the IBS-N and healthy control groups (all r<0.35, P>0.05). (5) Totally 13 IBS-P patients received rifaximin therapy, in whom the symptoms of

Assessment of the capability of a gelling complex made of tara gum and the exopolysaccharides produced by the microorganism Streptococcus thermophilus ST10 to prospectively restore the gut physiological barrier: a pilot study.

PubMed

Del Piano, Mario; Balzarini, Marco; Carmagnola, Stefania; Pagliarulo, Michela; Tari, Roberto; Nicola, Stefania; Deidda, Francesca; Pane, Marco

2014-01-01

(d45). The monosaccharide composition of EPSs was used to quantify the possible contribution of tara gum to the amount of polysaccharides detected in the faecal material. Intestinal permeability was evaluated at the same time by means of the lactitol/mannitol ratio (small intestine permeability) and sucralose concentration (colonic permeability) in urine specimens sampled after specified times. A statistical comparison was made between the concentration of EPSs, the lactulose/mannitol ratio, and the amount of excreted sucralose in the 2 groups at d0, d30, and d45. In the active group, supplementation with S. thermophilus ST10 and tara gum was able to significantly increase the faecal EPSs concentration compared with placebo (from 0.169 mg/g to 0.633 mg/g after 30 d, P<0.001). An interesting decrease in intestinal permeability, both of the small bowel and in the colon, was also recorded. The L/M ratio diminished from 0.021 in the active group to 0.014 and 0.015 after 30 and 45 days, respectively (P=0.045 and P=0.033 compared with placebo). The sucralose concentration decreased from 35.8 mg to 27.9 mg and 29.1 mg (P=0.038 and P=0.026 compared with placebo) at the end of the supplementation period and after the follow-up, respectively. No significant differences were recorded in the placebo after 30 days or at the end of the follow-up. The association of the EPSs produced by S. thermophilus ST10 and tara gum seems capable of significantly improving the intestinal functional barrier in healthy subjects. A wider study in subjects presenting impaired gut permeability would be useful in the future to confirm the positive results from this pilot trial. In any case, our findings are consistent with the parallel increase in exopolysaccharide concentration in the faecal material, thus suggesting the effective ability of the strain used to secrete EPSs in the gut lumen. An innovative approach of this type may be useful in helping to restore the physiological barrier by means of