Fecal microbiota transplantation: past, present and future perspectives.

PubMed

Bibbò, Stefano; Ianiro, Gianluca; Gasbarrini, Antonio; Cammarota, Giovanni

2017-12-01

Gut microbiota is known to play a main role in regulating both health and disease in humans. Strategies for the therapeutic modulation of gut microbiota are therefore expected to give a relevant contribution in the management of disorders associated with its impairment. Among these options, one of the most renowned is fecal microbiota transplantation (FMT). A growing body of evidence showed clearly that FMT is an effective treatment against recurrent Clostridium difficile infection. Moreover, it was shown to be a promising therapy for the management of several noncommunicable disorders, including inflammatory bowel diseases and metabolic disorders. Standardization of procedural protocols for different disorders will surely increase the therapeutic power of FMT. The aim of this narrative review was to make an overview of methodology, indications, and future perspectives of FMT for the management of disorders associated with gut microbiota impairment.

Treating Clostridium difficile Infection with Fecal Microbiota Transplantation

PubMed Central

Bakken, Johan S.; Borody, Thomas; Brandt, Lawrence J.; Brill, Joel V.; Demarco, Daniel C.; Franzos, Marc Alaric; Kelly, Colleen; Khoruts, Alexander; Louie, Thomas; Martinelli, Lawrence P.; Moore, Thomas A.; Russell, George; Surawicz, Christina

2011-01-01

Clostridium difficile infection is increasing in incidence, severity, and mortality. Treatment options are limited and appear to be losing efficacy. Recurrent disease is especially challenging; extended treatment with oral vancomycin is becoming increasingly common but is expensive. Fecal microbiota transplantation (FMT) is safe, inexpensive, and effective; according to case and small series reports, about 90% of patients are cured. We discuss the rationale, methods, and use of FMT. PMID:21871249

Fecal microbiota transplantation in children with recurrent Clostridium difficile infection.

PubMed

Pierog, Anne; Mencin, Ali; Reilly, Norelle Rizkalla

2014-11-01

Clostridium difficile eradication using fecal microbiota transplantation (FMT) has been successful in adults but little information is available in pediatrics. We report 6 pediatric patients with refractory C. difficile cured by FMT with no recurrences to date. Our results demonstrate that FMT can be an effective treatment for refractory C. difficile infection in pediatrics. Long-term safety and efficacy need to be studied.

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

PubMed Central

Hudson, Lauren E.; Anderson, Sarah E.; Corbett, Anita H.

2016-01-01

SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases. PMID:27856521

Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring.

PubMed

McCormack, Ursula M; Curião, Tânia; Wilkinson, Toby; Metzler-Zebeli, Barbara U; Reyer, Henry; Ryan, Tomas; Calderon-Diaz, Julia A; Crispie, Fiona; Cotter, Paul D; Creevey, Christopher J; Gardiner, Gillian E; Lawlor, Peadar G

2018-01-01

Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring's intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia , respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from highly feed

Fecal Microbiota Transplantation for Refractory Clostridium difficile Colitis in Solid Organ Transplant Recipients

PubMed Central

Friedman-Moraco, R. J.; Mehta, A. K.; Lyon, G. M.; Kraft, C. S.

2015-01-01

Fecal microbiota transplantation (FMT) has been shown to be safe and efficacious in individuals with refractory Clostridium difficile . It has not been widely studied in individuals with immunosuppression due to concerns about infectious complications. We describe two solid organ transplant recipients, one lung and one renal, in this case report that both had resolution of their diarrhea caused by C. difficile after FMT. Both recipients required two FMTs to achieve resolution of their symptoms and neither had infectious complications. Immunosuppressed individuals are at high risk for acquisition of C. difficile and close monitoring for infectious complications after FMT is necessary, but should not preclude its use in patients with refractory disease due to C. difficile . Sequential FMT may be used to achieve cure in these patients with damaged microbiota from antibiotic use and immunosuppression. PMID:24433460

Fecal Microbiota Transplantation in Inflammatory Bowel Disease.

PubMed

Reinisch, Walter

2017-01-01

The etiology of inflammatory bowel disease (IBD) is unknown, but it is thought to arise from an aberrant immune response to a change in colonic environment in a genetically susceptible individual. The intestinal microbiota are located at the complex interface of the epithelial barrier and are sensitive to changes in environmental factors, such as diets, drugs or smoking and signals derived from the intestinal immune system and the gut-brain axis. In patients with IBD, an imbalance in the structural and/or functional configuration of the intestinal microbiota leading to the disruption of the host-microorganism homeostasis (dysbiosis) has been reproducibly reported. As animal models of IBD require gut bacteria to induce inflammation, it is hypothesized that the dysbiosis observed in patients is not only a surrogate of changes at the intestinal barrier but also a potential cause or at least enhancer of the mucosal inflammatory process. That burgeoning notion has stimulated thoughts to modify the intestinal microbiota and rekindled interest in previous work on the efficacy of antibiotics in patients with IBD. The feasibility and tremendous success of fecal microbiota transplantation (FMT) to treat antibiotic resistant Clostridium difficile has finally paved the way to embark into the unchartered territory of IBD using FMT. Different routes and number of administrations, choices of donors, disease status and permitted therapies might have contributed to mixed results, particularly from the so far published randomized controlled trials. However, microbiome analysis suggests that a durable transplantation of donor bacteria to the host appears feasible and might be associated with a higher likelihood of response. On the other hand, this raises the concern of transplanting not only anti-inflammatory active bacteria and their products, but also not-yet-known dispositions for other diseases including cancer. Attempts are being made to better characterize those components of

Fecal microbiota transplantation in puppies with canine parvovirus infection

PubMed Central

Pereira, Giorgio Q.; Gomes, Lucas A.; Santos, Iago S.; Alfieri, Alice F.; Weese, J. S.

2018-01-01

Background Diarrhea associated with parvovirus infection is common in dogs. Supportive care is the mainstay of treatment, but recovery may be prolonged and mortality rate can be high. Modification of the intestinal bacterial microbiota has been promising in human and veterinary medicine as an adjunctive treatment of various enteric diseases. Objectives To investigate the safety and efficacy of fecal microbiota transplantation (FMT) on the clinical recovery of puppies with acute hemorrhagic diarrhea syndrome. Animals Sixty‐six puppies with parvovirus infection were evaluated at 2 veterinary hospitals. Methods Randomized clinical trial. Puppies were randomly distributed into 2 groups: standard treatment (STD) and standard treatment + FMT (STD + FMT). The STD puppies (n = 33) received only treatment with IV fluids and antimicrobials and the STD + FMT puppies (n = 33) received FMT in addition to standard treatment. For FMT, 10 g of feces from a healthy dog diluted in 10 mL of saline were administered rectally 6‐12 hours post‐admission. Results Among survivors, treatment with FMT was associated with faster resolution of diarrhea (P < .001) and shorter hospitalization time (P = .001; median, 3 days in STD + FMT; median, 6 days in STD) compared to standard treatment. Mortality in STD was 36.4% (12/33) as compared to 21.2% (7/33) in puppies treated with FMT, but there was no statistical difference between groups (P = .174). Polymerase chain reaction indicated that all animals carried canine parvovirus, strain CPV‐2b. Conclusions Fecal microbiota transplantation in parvovirus‐infected puppies was associated with faster resolution of diarrhea. PMID:29460302

Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring

PubMed Central

2018-01-01

ABSTRACT Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring’s intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia, respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation.

PubMed

Kim, Ji Eun; Gweon, Tae-Geun; Yeo, Chang Dong; Cho, Young-Seok; Kim, Gi Jun; Kim, Jae Young; Kim, Jong Wook; Kim, Hyunho; Lee, Hye Won; Lim, Taeseok; Ham, Hyoju; Oh, Hyun Jin; Lee, Yeongbok; Byeon, Jaeho; Park, Sung Soo

2014-09-21

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

Step-up fecal microbiota transplantation (FMT) strategy

PubMed Central

Cui, Bota; Li, Pan; Xu, Lijuan; Peng, Zhaoyuan; Xiang, Jie; He, Zhi; Zhang, Ting; Ji, Guozhong; Nie, Yongzhan; Wu, Kaichun; Fan, Daiming; Zhang, Faming

2016-01-01

ABSTRACT Gut dysbiosis is a characteristic of inflammatory bowel disease (IBD) and is believed to play a role in the pathogenesis of IBD. Fecal microbiota transplantation (FMT) is an effective strategy to restore intestinal microbial diversity and has been reported to have a potential therapeutic value in IBD. Our recent study reported a holistic integrative therapy called “step-up FMT strategy,” which was beneficial in treating steroid-dependent IBD patients. This strategy consists of scheduled FMTs combined with steroids, anti-TNF-α antibody treatment or enteral nutrition. Herein, we will elaborate the strategy thoroughly, introducing the concept, potential indication, methodology, and safety of “step-up FMT strategy” in detail. PMID:26939622

Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.

PubMed

Smits, Loek P; Kootte, Ruud S; Levin, Evgeni; Prodan, Andrei; Fuentes, Susana; Zoetendal, Erwin G; Wang, Zeneng; Levison, Bruce S; Cleophas, Maartje C P; Kemper, E Marleen; Dallinga-Thie, Geesje M; Groen, Albert K; Joosten, Leo A B; Netea, Mihai G; Stroes, Erik S G; de Vos, Willem M; Hazen, Stanley L; Nieuwdorp, Max

2018-03-26

Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d 6 -choline and d 3 -carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18 F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. URL: http://www.trialregister.nl. Unique identifier: NTR 4338. © 2018 The Authors. Published on

Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Primer for Internists.

PubMed

Syal, Gaurav; Kashani, Amir; Shih, David Q

2018-03-29

Inflammatory bowel disease consists of disorders characterized by chronic idiopathic bowel inflammation. The concept of host-gut-microbiome interaction in the pathogenesis of various complex immune-mediated chronic diseases, including inflammatory bowel disease, has recently generated immense interest. Mounting evidence confirms alteration of intestinal microflora in patients with inflammatory bowel disease. Thus, restoration of normal gut microbiota has become a focus of basic and clinical research in recent years. Fecal microbiota transplantation is being explored as one such therapeutic strategy and has shown encouraging results in the management of patients with inflammatory bowel disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Fecal microbiota transplantation in the treatment of Clostridium difficile infection: state of the art and literature review.

PubMed

Messias, Bruno Amantini; Franchi, Bárbara Freitas; Pontes, Pedro Henrique; Barbosa, Daniel Átila DE Andrade Medeiros; Viana, César Augusto Sanita

2018-01-01

Clostridium difficile infection is a common complication following intestinal dysbiosis caused by abusive antibiotic use. It presents medical importance due to the high rates of recurrence and morbidity. Fecal microbiota transplantation is an effective alternative for the treatment of recurrent and refractory C. difficile infection and consists of introducing the intestinal microbiota from a healthy donor into a patient with this infection. The exact physiological mechanism by which fecal microbiota transplantation alters the intestinal microbiota is not well established, but it is clear that it restores the diversity and structure of the microbiota by promoting increased resistance to colonization by C. difficile. Several routes of transplant administration are being studied and used according to the advantages presented. All forms of application had a high cure rate, and the colonoscopic route was the most used. No relevant complications and adverse events have been documented, and the cost-effectiveness over conventional treatment has proven advantageous. Despite its efficacy, it is not commonly used as initial therapy, and more studies are needed to establish this therapy as the first option in case of refractory and recurrent Clostridium difficileinfection.

FECAL MICROBIOTA TRANSPLANT RESTORES MUCOSAL INTEGRITY IN A MURINE MODEL OF BURN INJURY

PubMed Central

Kuethe, Joshua W.; Armocida, Stephanie M.; Midura, Emily F.; Rice, Teresa C.; Hildeman, David A.; Healy, Daniel P.; Caldwell, Charles C.

2016-01-01

The gut microbiome is a community of commensal organisms that are known to play a role in nutrient production as well as gut homeostasis. The composition of the gut flora can be affected by many factors; however, the impact of burn injury on the microbiome is not fully known. Here, we hypothesized that burn-induced changes to the microbiome would impact overall colon health. After scald-burn injury, cecal samples were analyzed for aerobic and anaerobic colony forming units, bacterial community, and butyrate levels. In addition, colon and total intestinal permeabilities were determined. These parameters were further determined in a germ-reduced murine model. Following both burn injury and germ reduction, we observed decreases in aerobic and anaerobic bacteria, increased colon permeability and no change to small intestinal permeability. After burn injury, we further observed a significant decrease in the butyrate producing bacteria R. Gnavus, C. Eutactus, and Roseburia species as well as decreases in colonic butyrate. Finally, in mice that underwent burn followed by fecal microbiota transplant, bacteria levels and mucosal integrity were restored. Altogether our data demonstrate that burn injury can alter the microbiome leading to decreased butyrate levels and increased colon permeability. Of interest, fecal microbiota transplant treatment was able to ameliorate the burn-induced changes in colon permeability. Thus, fecal transplantation may represent a novel therapy in restoring colon health after burn injury. PMID:26682948

Fecal microbiota transplantation in metabolic syndrome: History, present and future

PubMed Central

de Groot, P. F.; de Clercq, N. C.; Nieuwdorp, M.

2017-01-01

ABSTRACT The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome. With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects. PMID:28609252

Fecal microbiota transplantation in metabolic syndrome: History, present and future.

PubMed

de Groot, P F; Frissen, M N; de Clercq, N C; Nieuwdorp, M

2017-05-04

The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome. With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects.

Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota.

PubMed

Staley, Christopher; Vaughn, Byron P; Graiziger, Carolyn T; Singroy, Stephanie; Hamilton, Matthew J; Yao, Dan; Chen, Chi; Khoruts, Alexander; Sadowsky, Michael J

2017-05-04

Fecal microbiota transplantation (FMT) is a highly effective treatment of recurrent and recalcitrant Clostridium difficile infection (rCDI). In a recent study oral-delivery of encapsulated, freeze-dried donor material, resulted in comparable rates of cure to colonoscopic approaches. Here we characterize shifts in the fecal bacterial community structure of patients treated for rCDI using encapsulated donor material. Prior to FMT, patient fecal samples showed declines in diversity and abundance of Firmicutes and Bacteroidetes, with concurrent increases in members of the Proteobacteria, specifically Enterobacteriaceae. Moreover, patients who experienced recurrence of CDI within the 2-month clinical follow-up had greater abundances of Enterobacteriaceae and did not show resolution of dysbioses. Despite resolution of rCDI following oral-administration of encapsulated fecal microbiota, community composition was slow to return to a normal donor-like assemblage. Post-FMT taxa within the Firmicutes showed rapid increases in relative abundance and did not vary significantly over time. Conversely, Bacteroidetes taxa only showed significant increases in abundance after one month post-FMT, corresponding to significant increases in the community attributable to the donors. Changes in the associations among dominant OTUs were observed at days, weeks, and months post-FMT, suggesting shifts in community dynamics may be related to the timing of increases in abundance of specific taxa. Administration of encapsulated, freeze-dried, fecal microbiota to rCDI patients resulted in restoration of bacterial diversity and resolution of dysbiosis. However, shifts in the fecal microbiome were incremental rather than immediate, and may be driven by changes in community dynamics reflecting changes in the host environment.

Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond.

PubMed

Borody, Thomas J; Peattie, Debra; Mitchell, Scott W

2015-07-06

Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases.

Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond

PubMed Central

Borody, Thomas J.; Peattie, Debra; Mitchell, Scott W.

2015-01-01

Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases. PMID:27025624

Fecal microbiota transplantation and its potential therapeutic uses in gastrointestinal disorders.

PubMed

Heath, Ryan D; Cockerell, Courtney; Mankoo, Ravinder; Ibdah, Jamal A; Tahan, Veysel

2018-01-01

Typical human gut flora has been well characterized in previous studies and has been noted to have significant differences when compared with the typical microbiome of various disease states involving the gastrointestinal tract. Such diseases include Clostridium difficile colitis, inflammatory bowel disease, functional bowel syndromes, and various states of liver disease. A growing number of studies have investigated the use of a fecal microbiota transplant as a potential therapy for these disease states.

Fecal microbiota transplantation and its potential therapeutic uses in gastrointestinal disorders

PubMed Central

Heath, Ryan D.; Cockerell, Courtney; Mankoo, Ravinder; Ibdah, Jamal A.; Tahan, Veysel

2018-01-01

Typical human gut flora has been well characterized in previous studies and has been noted to have significant differences when compared with the typical microbiome of various disease states involving the gastrointestinal tract. Such diseases include Clostridium difficile colitis, inflammatory bowel disease, functional bowel syndromes, and various states of liver disease. A growing number of studies have investigated the use of a fecal microbiota transplant as a potential therapy for these disease states. PMID:29607440

Successful Fecal Microbiota Transplantation in a Patient with Severe Complicated Clostridium difficile Infection after Liver Transplantation.

PubMed

Schneider, Kai Markus; Wirtz, Theresa H; Kroy, Daniela; Albers, Stefanie; Neumann, Ulf Peter; Strowig, Till; Sellge, Gernot; Trautwein, Christian

2018-01-01

Clostridium difficile infection (CDI) represents one of the most common healthcare-associated infections. Due to increasing numbers of recurrences and therapy failures, CDI has become a major disease burden. Studies have shown that fecal microbiota transplantation (FMT) can both be a safe and highly efficacious therapy for patients with therapy-refractory CDI. However, patients undergoing solid organ transplantation are at high risk for CDI due to long-term immunosuppression, previous antibiotic therapy, and proton pump inhibitor use. Additionally, these patients may be especially prone to adverse events related to FMT. Here, we report a successful FMT in a patient with severe therapy-refractory CDI after liver transplantation.

A repeat offender: Recurrent extraintestinal Clostridium difficile infection following fecal microbiota transplantation.

PubMed

Gardiner, Bradley J; Thorpe, Cheleste M; Pinkham, Nicholas V; McDermott, Laura A; Walk, Seth T; Snydman, David R

2018-06-01

Extraintestinal infection with Clostridium difficile has been reported but remains uncommon. Treatment of this unusual complication is complex given the limitations of current therapeutic options. Here we report a novel case of recurrent extraintestinal C. difficile infection that occurred following fecal microbiota transplantation. Using whole genome sequencing, we confirmed recrudescence rather than reinfection was responsible. The patient ultimately responded to prolonged, targeted antimicrobial therapy informed by susceptibility testing. Copyright © 2018 Elsevier Ltd. All rights reserved.

THE POWER OF POOP: FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIUM DIFFICILE INFECTION

PubMed Central

EDMOND, MICHAEL B.

2016-01-01

The human gut is colonized with 200 to 1,000 bacterial species. Administration of antibiotics reduces the diversity of the intestinal microbiota, reduces colonization resistance, and can lead to infection with Clostridium difficile. These infections have become more prevalent and increasingly patients are experiencing multiple recurrences that are incurable with standard treatment. Although fecal microbiota transplantation (FMT) has been used for centuries in human and veterinary medicine, only recently has it be shown to be highly effective for recurrent C. difficile infection. The goal of FMT is to re-introduce a complete, stable community of gut microorganisms to repair or replace the disrupted native microbiota. FMT can be delivered via nasoenteric tube, colonoscopy, or enema. Despite a cure rate approximating 90%, many barriers to FMT have limited its availability to patients. The recent development of a not-for-profit stool bank has helped to make this therapy more accessible. Additional indications for FMT are currently under investigation. PMID:28066039

THE POWER OF POOP: FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIUM DIFFICILE INFECTION.

PubMed

Edmond, Michael B

2016-01-01

The human gut is colonized with 200 to 1,000 bacterial species. Administration of antibiotics reduces the diversity of the intestinal microbiota, reduces colonization resistance, and can lead to infection with Clostridium difficile . These infections have become more prevalent and increasingly patients are experiencing multiple recurrences that are incurable with standard treatment. Although fecal microbiota transplantation (FMT) has been used for centuries in human and veterinary medicine, only recently has it be shown to be highly effective for recurrent C. difficile infection. The goal of FMT is to re-introduce a complete, stable community of gut microorganisms to repair or replace the disrupted native microbiota. FMT can be delivered via nasoenteric tube, colonoscopy, or enema. Despite a cure rate approximating 90%, many barriers to FMT have limited its availability to patients. The recent development of a not-for-profit stool bank has helped to make this therapy more accessible. Additional indications for FMT are currently under investigation.

Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.

PubMed

Weingarden, Alexa R; Chen, Chi; Bobr, Aleh; Yao, Dan; Lu, Yuwei; Nelson, Valerie M; Sadowsky, Michael J; Khoruts, Alexander

2014-02-15

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.

Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway.

PubMed

Sun, Meng-Fei; Zhu, Ying-Li; Zhou, Zhi-Lan; Jia, Xue-Bing; Xu, Yi-Da; Yang, Qin; Cui, Chun; Shen, Yan-Qin

2018-05-01

Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs, alleviated physical impairment, and increased striatal DA and 5-HT content of PD mice. Further, FMT reduced the activation of microglia and astrocytes in the substantia nigra, and reduced expression of TLR4/TNF-α signaling pathway components in gut and brain. Our study demonstrates that gut microbial dysbiosis is involved in PD pathogenesis, and FMT can protect PD mice by suppressing neuroinflammation and reducing TLR4/TNF-α signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

Economic evaluation of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection in Australia.

PubMed

Merlo, Gregory; Graves, Nicholas; Brain, David; Connelly, Luke B

2016-12-01

Clostridium difficile is the most common cause of hospital-acquired diarrhea in Australia. In 2013, a randomized controlled trial demonstrated the effectiveness of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The aim of this study is to evaluate the cost-effectiveness of fecal microbiota transplantation-via either nasoduodenal or colorectal delivery-compared with vancomycin for the treatment of recurrent CDI in Australia. A Markov model was developed to compare the cost-effectiveness of fecal microbiota transplantation compared with standard antibiotic therapy. A literature review of clinical evidence informed the structure of the model and the choice of parameter values. Clinical effectiveness was measured in terms of quality-adjusted life years. Uncertainty in the model was explored using probabilistic sensitivity analysis. Both nasoduodenal and colorectal FMT resulted in improved quality of life and reduced cost compared with vancomycin. The incremental effectiveness of either FMT delivery compared with vancomycin was 1.2 (95% CI: 0.1, 2.3) quality-adjusted life years, or 1.4 (95% CI: 0.4, 2.4) life years saved. Treatment with vancomycin resulted in an increased cost of AU$4094 (95% CI: AU$26, AU$8161) compared with nasoduodenal delivery of FMT and AU$4045 (95% CI: -AU$33, AU$8124) compared with colorectal delivery. The mean difference in cost between colorectal and nasoduodenal FMT was not significant. If FMT, rather than vancomycin, became standard care for recurrent CDI in Australia, the estimated national healthcare savings would be over AU$4000 per treated person, with a substantial increase in quality of life. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Fecal Microbiota Transplantation Inhibits Multidrug-Resistant Gut Pathogens: Preliminary Report Performed in an Immunocompromised Host.

PubMed

Biliński, Jarosław; Grzesiowski, Paweł; Muszyński, Jacek; Wróblewska, Marta; Mądry, Krzysztof; Robak, Katarzyna; Dzieciątkowski, Tomasz; Wiktor-Jedrzejczak, Wiesław; Basak, Grzegorz W

2016-06-01

Colonization of the gastrointestinal tract with multidrug-resistant (MDR) bacteria is a consequence of gut dysbiosis. We describe the successful utilization of fecal microbiota transplantation to inhibit Klebsiella pneumoniae MBL(+) and Escherichia coli ESBL(+) gut colonization in the immunocompromised host as a novel tool in the battle against MDR microorganisms. ClinicalTrials.gov identifier NCT02461199.

Endoscopic peroral jejunal fecal microbiota transplantation.

PubMed

Link, Alexander; Lachmund, Tim; Schulz, Christian; Weigt, Jochen; Malfertheiner, Peter

2016-11-01

Fecal microbiota transplantation (FMT) is a valuable treatment modality for recurrent Clostridium difficile (C. difficile) colitis. Multiple questions including the best delivery route and volume remain unanswered. Here, we report a case series of high-volume FMT using endoscopic jejunal application route. In prospective observational study, FMT was performed using fresh specimen from healthy unrelated donors to the patients with recurrent or refractory C. difficile colitis. Selection of the route was based on the patient's preferences. Specimens of at least 50g were dissolved in 500ml of electrolyte solution and administered using endoscope directly in jejunum. All procedures led to cure of C. difficile colitis. With exception of one case the procedure was well tolerated. In two cases, we observed FMT-reflux into the stomach despite deep jejunal application and in single case the FMT-reflux led to tracheal aspiration and severe pneumonia. High-volume FMT via endoscopic jejunal route is an effective treatment option that is well tolerated and easy to perform. Nevertheless, aspiration is potential life-threatening event that needs to be kept in mind during the FMT-procedure. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Intestinal microbial and metabolic alterations following successful fecal microbiota transplant for D-lactic acidosis.

PubMed

Bulik-Sullivan, Emily C; Roy, Sayanty; Elliott, Ryan J; Kassam, Zain; Lichtman, Steven N; Carroll, Ian M; Gulati, Ajay S

2018-06-12

Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.

Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile.

PubMed

Bakker, Guido J; Nieuwdorp, Max

2017-08-01

The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.

Efficacy of fecal microbiota transplantation in 2 children with recurrent Clostridium difficile infection and its impact on their growth and gut microbiome.

PubMed

Walia, Ritu; Garg, Shashank; Song, Yang; Girotra, Mohit; Cuffari, Carmen; Fricke, Wolfgang Florian; Dutta, Sudhir K

2014-11-01

Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.

Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers.

PubMed

Li, Bo; Guo, Kenan; Zeng, Li; Zeng, Benhua; Huo, Ran; Luo, Yuanyuan; Wang, Haiyang; Dong, Meixue; Zheng, Peng; Zhou, Chanjuan; Chen, Jianjun; Liu, Yiyun; Liu, Zhao; Fang, Liang; Wei, Hong; Xie, Peng

2018-01-31

Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about "depression microbes" impacting on liver metabolism.

Fecal Microbiota Transplantation: A Review of Emerging Indications Beyond Relapsing Clostridium difficile Toxin Colitis

PubMed Central

Lee, Woo Jung; Lattimer, Lakshmi D. N.; Stephen, Sindu; Borum, Marie L.

2015-01-01

The symbiotic relationship between gut microbiota and humans has been forged over many millennia. This relationship has evolved to establish an intimate partnership that we are only beginning to understand. Gut microbiota were once considered pathogenic, but the concept of gut microbiota and their influence in human health is undergoing a major paradigm shift, as there is mounting evidence of their impact in the homeostasis of intestinal development, metabolic activities, and the immune system. The disruption of microbiota has been associated with many gastrointestinal and nongastrointestinal diseases, and the reconstitution of balanced microbiota has been postulated as a potential therapeutic strategy. Fecal microbiota transplantation (FMT), a unique method to reestablish a sustained balance in the disrupted microbiota of diseased intestine, has demonstrated great success in the treatment of recurrent Clostridium difficile infection and has gained increasing acceptance in clinical use. The possibility of dysfunctional micro-biota playing a causative role in other gastrointestinal and nongas-trointestinal diseases, therefore, has also been raised, and there are an increasing number of studies supporting this hypothesis. FMT is emerging as a feasible therapeutic option for several diseases; however, its efficacy remains in question, given the lack of clinical trial data. Altering microbiota with FMT holds great promise, but much research is needed to further define FMT’s therapeutic role and optimize the microbiota delivery system. PMID:27099570

Fecal Microbiota Transplantation: A Review of Emerging Indications Beyond Relapsing Clostridium difficile Toxin Colitis.

PubMed

Jung Lee, Woo; Lattimer, Lakshmi D N; Stephen, Sindu; Borum, Marie L; Doman, David B

2015-01-01

The symbiotic relationship between gut microbiota and humans has been forged over many millennia. This relationship has evolved to establish an intimate partnership that we are only beginning to understand. Gut microbiota were once considered pathogenic, but the concept of gut microbiota and their influence in human health is undergoing a major paradigm shift, as there is mounting evidence of their impact in the homeostasis of intestinal development, metabolic activities, and the immune system. The disruption of microbiota has been associated with many gastrointestinal and nongastrointestinal diseases, and the reconstitution of balanced microbiota has been postulated as a potential therapeutic strategy. Fecal microbiota transplantation (FMT), a unique method to reestablish a sustained balance in the disrupted microbiota of diseased intestine, has demonstrated great success in the treatment of recurrent Clostridium difficile infection and has gained increasing acceptance in clinical use. The possibility of dysfunctional micro-biota playing a causative role in other gastrointestinal and nongas-trointestinal diseases, therefore, has also been raised, and there are an increasing number of studies supporting this hypothesis. FMT is emerging as a feasible therapeutic option for several diseases; however, its efficacy remains in question, given the lack of clinical trial data. Altering microbiota with FMT holds great promise, but much research is needed to further define FMT's therapeutic role and optimize the microbiota delivery system.

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation.

PubMed

Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi

2017-04-01

Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides , Enterobacteriaceae , Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae , Lactobacillaceae , Clostridiaceae , Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.

Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice.

PubMed

Ferrere, Gladys; Wrzosek, Laura; Cailleux, Frédéric; Turpin, Williams; Puchois, Virginie; Spatz, Madeleine; Ciocan, Dragos; Rainteau, Dominique; Humbert, Lydie; Hugot, Cindy; Gaudin, Françoise; Noordine, Marie-Louise; Robert, Véronique; Berrebi, Dominique; Thomas, Muriel; Naveau, Sylvie; Perlemuter, Gabriel; Cassard, Anne-Marie

2017-04-01

Alcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities to test the efficiency of two complementary strategies (fecal microbiota transplantation and prebiotic treatment) to reverse dysbiosis and prevent ALD. Mice were fed alcohol in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota transplantation was performed with fresh feces from alcohol-resistant donor mice to alcohol-sensitive receiver mice three times a week. Another group of mice received pectin during the entire alcohol consumption period. Ethanol induced steatosis and liver inflammation, which were associated with disruption of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM analysis showed that the proportion of Bacteroides was specifically lower in alcohol-sensitive mice (p<0.05). Principal coordinate analysis showed that the IM of sensitive and resistant mice clustered differently. We targeted IM using two different strategies to prevent alcohol-induced liver lesions: (1) pectin treatment which induced major modifications of the IM, (2) fecal microbiota transplantation which resulted in an IM very close to that of resistant donor mice in the sensitive recipient mice. Both methods prevented steatosis, liver inflammation, and restored gut homeostasis. Manipulation of IM can prevent alcohol-induced liver injury. The IM should be considered as a new therapeutic target in ALD. Sensitivity to alcoholic liver disease (ALD) is driven by intestinal microbiota in alcohol fed mice. Treatment of mice with alcohol-induced liver lesions by fecal transplant from alcohol fed mice resistant to ALD or with prebiotic (pectin) prevents ALD. These findings open new possibilities for treatment of human

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation

PubMed Central

Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi

2017-01-01

Background Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. Methods We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Results Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. Conclusions The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes. PMID:28405600

Gut microbiota in cirrhotic liver transplant candidates.

PubMed

Grąt, Michał; Hołówko, Wacław; Gałecka, Mirosława; Grąt, Karolina; Szachtaz, Patrycja; Lewandowsk, Zbigniew; Kosińska, Irena; Schmidts, Marcin; Olejnik-Schmidt, Agnieszka; Krawczyk, Marek

2014-09-01

The purpose of this study was to evaluate the gut microflora of liver transplant candidates. Fecal microflora of 20 cirrhotic liver transplant candidates was analyzed basing on prospectively collected stool samples. The results were compared with those of 20 non-cirrhotic patients with liver disease and/or abnormal liver function tests, 20 patients with Crohn’s disease, and 20 patients without any gastrointestinal disease. Moreover, correlations between particular counts of microbiota, as well as between microbial counts and stool pH were examined. The pattern of fecal microbiota of liver transplant candidates was characterized by increased counts of lactobacilli (p=0.001), including hydrogen peroxide producing strains (p=0.008). In these patients, lactobacilli were positively correlated to enterococci (p=0.006) and bifidobacteria (p=0.004). No correlations other than those observed for lactobacilli in general were observed between hydrogen peroxide producing lactobacilli and the remaining microbiota. Increased yeast and Escherichia coli counts were associated with a tendency towards lower (p=0.095) and higher (p=0.072) stool pH, respectively. Surprisingly, gut microflora of liver transplant candidates with cirrhosis is particularly enriched with lactobacilli, including hydrogen peroxide producing strains. Thus, the use of other potentially beneficial microorganisms, such as particular yeast strains, might be more appropriate for these patients.

Microbiota transplantation: concept, methodology and strategy for its modernization.

PubMed

Zhang, Faming; Cui, Bota; He, Xingxiang; Nie, Yuqiang; Wu, Kaichun; Fan, Daiming

2018-05-01

Fecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts' perspectives.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. We conducted this systematic review to assess the efficacy and safety of FMT in UC. PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.

Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota.

PubMed

Zhou, Da; Pan, Qin; Shen, Feng; Cao, Hai-Xia; Ding, Wen-Jin; Chen, Yuan-Wen; Fan, Jian-Gao

2017-05-08

Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined. Our results showed that after FMT, the gut microbiota disturbance was corrected in HFD-fed mice with elevated abundances of the beneficial bacteria Christensenellaceae and Lactobacillus. FMT also increased butyrate concentrations of the cecal content and the intestinal tight junction protein ZO-1, resulting in relief of endotoxima in HFD-fed mice. Steatohepatitis was alleviated after FMT, as indicated by a significant decrease in intrahepatic lipid accumulation (reduced Oli-red staining, decreased intrahepatic triglyceride and cholesterol), intrahepatic pro-inflammatory cytokines, and the NAS score. Accordingly, intrahepatic IFN-γ and IL-17 were decreased, but Foxp3, IL-4 and IL-22 were increased after FMT intervention. These data indicate that FMT attenuated HFD-induced steatohepatitis in mice via a beneficial effect on the gut microbiota.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis

PubMed Central

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Background Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. Objective We conducted this systematic review to assess the efficacy and safety of FMT in UC. Data Sources PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. Data Extraction and Synthesis We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Results Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. Conclusion FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition. PMID:27295210

Ensuring the safe and effective FDA regulation of fecal microbiota transplantation

PubMed Central

Sachs, Rachel E.; Edelstein, Carolyn A.

2015-01-01

Scientists, policymakers, and medical professionals alike have become increasingly worried about the rise of antibiotic resistance, and the growing number of infections due to bacteria like Clostridium difficile, which cause a significant number of deaths and are imposing increasing costs on our health care system. However, in the last few years, fecal microbiota transplantation (FMT), the transplantation of stool from a healthy donor into the bowel of a patient, has emerged as a startlingly effective means to treat recurrent C. difficile infections. At present, the FDA is proposing to regulate FMT as a biologic drug. However, this proposed classification is both underregulatory and overregulatory. The FDA's primary goal is to ensure that patients have access to safe, effective treatments—and as such they should regulate some aspects of FMT more stringently than they propose to, and others less so. This essay will examine the nature of the regulatory challenges the FDA will face in deciding to regulate FMT as a biologic drug, and will then evaluate available policy alternatives for the FDA to pursue, ultimately concluding that the FDA ought to consider adopting a hybrid regulatory model as it has done in the case of cord blood. PMID:27774199

From Stool Transplants to Next-generation Microbiota Therapeutics

PubMed Central

2014-01-01

The epidemic of Clostridium difficile infection fueled by new virulent strains of the organism has led to increased use of fecal microbiota transplantation (FMT). The procedure is effective for even the most desperate cases, after failure of multiple courses of antibiotics. The approach recognizes microbiota to be integral to normal human physiology, and microbiota being used in FMT represents a new class of therapeutics. Imbalance in the composition and altered activity of the microbiota are associated with many diseases. Consequently, there is growing interest in applying FMT to non-C. difficile indications. However, this may succeed only if microbiota therapeutics are developed systematically, based on mechanistic understanding, and applying updo-date principles of microbial ecology. We discuss two pathways in development of this new therapeutic class: whole microbial communities separated from donor stool and an assembly of specific fecal microorganisms grown in vitro. PMID:24412527

Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease.

PubMed

Newman, Krista M; Rank, Kevin M; Vaughn, Byron P; Khoruts, Alexander

2017-05-04

We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.

Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis.

PubMed

Qin, Chenjie; Zhang, Huilu; Zhao, Linghao; Zeng, Min; Huang, Weijian; Fu, Gongbo; Zhou, Weiping; Wang, Hongyang; Yan, Hexin

2017-11-29

Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine (DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium (DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine, the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota.

Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile.

PubMed

Kumar, Ranjit; Maynard, Craig L; Eipers, Peter; Goldsmith, Kelly T; Ptacek, Travis; Grubbs, J Aaron; Dixon, Paula; Howard, Donna; Crossman, David K; Crowley, Michael R; Benjamin, William H; Lefkowitz, Elliot J; Weaver, Casey T; Rodriguez, J Martin; Morrow, Casey D

2016-01-13

Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%. We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early

Gut Microbiota Dysbiosis and Diarrhea in Kidney Transplant Recipients.

PubMed

Lee, John Richard; Magruder, Matthew; Zhang, Lisa; Westblade, Lars F; Satlin, Michael J; Robertson, Amy; Edusei, Emmanuel; Crawford, Carl; Ling, Lilan; Taur, Ying; Schlueter, Jonas; Lubetzky, Michelle; Dadhania, Darshana; Pamer, Eric; Suthanthiran, Manikkam

2018-06-19

Post-transplant diarrhea is associated with kidney allograft failure and death but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether post-transplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S rRNA gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with post-transplant diarrhea than in 112 fecal specimens from 46 recipients without post-transplant diarrhea. We found lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted p value ≤ 0.15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed PCR assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt to predict metagenomic functions, we found diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that post-transplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation.

PubMed

Jeon, Seong Ran; Chai, Jocelyn; Kim, Christiana; Lee, Christine H

2018-05-26

Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD. Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn's disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients' stools. FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.

Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in a Pediatric Heart Transplant Patient.

PubMed

Flannigan, Kyle L; Rajbar, Taylor; Moffat, Andrew; McKenzie, Leanna S; Dicke, Frank; Rioux, Kevin; Workentine, Matthew L; Louie, Thomas J; Hirota, Simon A; Greenway, Steven C

2017-01-01

The microbiome is increasingly recognized as an important influence on human health and many of the comorbidities that affect patients after solid organ transplantation (SOT) have been shown to involve changes in gut bacterial populations. Thus, microbiome changes in an individual patient may have important health implications after SOT but this area remains understudied. We describe changes in the composition of the fecal microbiome from a pediatric heart transplant recipient before and >2.5 years after he underwent repeated fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI). With both documented episodes of CDI, there was marked loss of bacterial diversity with overgrowth of Proteobacteria (>98.9% of phyla identified) associated with symptomatic colitis that was corrected after FMT. We hypothesize that a second CDI occurring after FMT was related to incomplete restoration of normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae . Following the second FMT, there was a gradual shift in gut bacterial composition coincident with the recipient developing lymphonodular hyperplasia of the colon and painless hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF). This case documents dynamic changes in the bacterial microbiome after FMT and suggests that MMF may influence the gut microbiome with consequences for the patient.

Systematic Review and Meta-analysis: Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis.

PubMed

Narula, Neeraj; Kassam, Zain; Yuan, Yuhong; Colombel, Jean-Frederic; Ponsioen, Cyriel; Reinisch, Walter; Moayyedi, Paul

2017-10-01

Changes in the colonic microbiota may play a role in the pathogenesis of ulcerative colitis (UC) and restoration of healthy gut microbiota may ameliorate disease. A systematic review and meta-analysis was conducted to assess fecal microbiota transplantation (FMT) as a treatment for active UC. A literature search was conducted to identify high-quality studies of FMT as a treatment for patients with UC. The primary outcome was combined clinical remission and endoscopic remission or response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Odds ratios with 95% confidence intervals (CIs) are reported. Overall, 4 studies with 277 participants were eligible for inclusion. Among 4 randomized controlled trials, FMT was associated with higher combined clinical and endoscopic remission compared with placebo (risk ratio UC not in remission was 0.80; 95% CI: 0.71-0.89) with a number needed to treat of 5 (95% CI: 4-10). There was no statistically significant increase in serious adverse events with FMT compared with controls (risk ratio adverse event was 1.4; 95% CI: 0.55-3.58). Among randomized controlled trials, short-term use of FMT shows promise as a treatment to induce remission in active UC based on the efficacy and safety observed. However, there remain many unanswered questions that require further research before FMT can be considered for use in clinical practice.

Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora.

PubMed

Wei, Yao; Gong, Jianfeng; Zhu, Weiming; Tian, Hongliang; Ding, Chao; Gu, Lili; Li, Ning; Li, Jieshou

2016-11-03

Fecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients. Three FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P = 0.042 and P = 0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment. Pectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC. Current Controlled Trial NCT02016469 . Registered 10 November 2013.

Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis.

PubMed

Philips, Cyriac Abby; Phadke, Nikhil; Ganesan, Karthik; Ranade, Shatakshi; Augustine, Philip

2018-06-21

Alcohol-induced intestinal dysbiosis is central to the development of the severe alcoholic liver disease. We present the first study to compare outcomes in patients of severe alcoholic hepatitis (SAH) on nutritional therapy, corticosteroids, pentoxifylline, and healthy donor fecal transplantation (FMT) and discuss distinct microbial community and microbiome metabolic functional changes after FMT. Out of 1271 liver disease patients, 809 (63.7%) were diagnosed to have the alcoholic liver disease, of which 51 patients (8 treated with corticosteroids, 17 with nutritional support only, 10 with pentoxifylline, 16 receiving FMT) were included. Clinical, biochemical parameters, liver disease, and alcoholic hepatitis severity scores at baseline and mortality at the end of 1 and 3 months were analyzed between groups. Stool microbiota (SM) analysis was performed for healthy controls (HC) and respective recipients after FMT. All the patients were male. The proportions of patients surviving at the end of 1 and 3 months in the steroids, nutrition, pentoxifylline, and FMT group were 63%, 47%, 40% and 75% [p = 0.179] and 38%, 29%, 30%, and 75% [p = 0.036], respectively. When compared with FMT, relative risk and hazard ratios for death were higher in all the other groups. Following FMT, distinct and beneficial modulation of SM and pathways of dysregulated metabolism, infections, inflammation, and oxidative stress in SAH patients were noted in tandem with improved clinical outcomes. Healthy donor FMT for SAH improves survival beyond what is offered by current therapies and can function as a cost-effective bridge to liver transplant (LT) or for improving transplant-free survival. Larger studies and randomized trials are unmet needs.

A proposed definition of microbiota transplantation for regulatory purposes

PubMed Central

Hoffmann, Diane E.; Palumbo, Francis B.; Rowthorn, Virginia; von Rosenvinge, Erik

2017-01-01

ABSTRACT The advent of fecal microbiota transplantation (FMT) and the prospect of other types of microbiota transplants (MT), e.g. vaginal, skin, oral and nasal, are challenging regulatory agencies. Although FDA is regulating FMT (as a biologic), there is currently no widely accepted or agreed upon scientific or legal definition of FMT or MT. The authors report on discussions regarding a definition of MT that took place among a working group of stakeholders convened under a National Institutes for Allergies and Infectious Diseases grant to address the regulation of MT. In arriving at a definition, the group considered the 1) nature of the material being transplanted; 2) degree of manipulation of the transferred materials prior to implantation; 3) ability to characterize the transplanted product using external techniques; and 4) origin of the stool product (single vs multiple donors). PMID:28318396

Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study

PubMed Central

Staley, Christopher; Hamilton, Matthew J.; Vaughn, Byron P.; Graiziger, Carolyn T.; Newman, Krista M.; Kabage, Amanda J.; Sadowsky, Michael J.; Khoruts, Alexander

2017-01-01

OBJECTIVES Fecal microbiota transplantation (FMT) is increasingly being used for treatment of recurrent Clostridium difficile infection (R-CDI) that cannot be cured with antibiotics alone. In addition, FMT is being investigated for a variety of indications where restoration or restructuring of the gut microbial community is hypothesized to be beneficial. We sought to develop a stable, freeze-dried encapsulated preparation of standardized fecal microbiota that can be used for FMT with ease and convenience in clinical practice and research. METHODS We systematically developed a lyophilization protocol that preserved the viability of bacteria across the taxonomic spectrum found in fecal microbiota and yielded physicochemical properties that enabled consistent encapsulation. We also treated a cohort of R-CDI patients with a range of doses of encapsulated microbiota and analyzed the associated changes in the fecal microbiome of the recipients. RESULTS The optimized lyophilized preparation satisfied all our preset goals for physicochemical properties, encapsulation ease, stability at different temperatures, and microbiota viability in vitro and in vivo (germ-free mice). The capsule treatment was administered to 49 patients. Overall, 43/49 (88%) of patients achieved a clinical success, defined as no recurrence of CDI over 2 months. Analysis of the fecal microbiome demonstrated near normalization of the fecal microbial community by 1 month following FMT treatment. The simplest protocol using the lowest dose (2.1–2.5×1011 bacteria in 2–3 capsules) without any colon purgative performed equally well in terms of clinical outcomes and microbiota engraftment. CONCLUSIONS A single administration of encapsulated, freeze-dried fecal microbiota from a healthy donor was highly successful in treating antibiotic-refractory R-CDI syndrome. PMID:28195180

Characterizing the fecal microbiota of infants with botulism.

PubMed

Shirey, T Brian; Dykes, Janet K; Lúquez, Carolina; Maslanka, Susan E; Raphael, Brian H

2015-11-23

Infant botulism is the most prevalent form of botulism in the USA, representing 68.5 % of cases reported from 2001-2012. Infant botulism results when botulinum toxin-producing clostridia (BTPC) colonize the infant gut with concomitant in vivo production of the highly potent botulinum neurotoxin (BoNT). The gut microbiota of infants with botulism is largely uncharacterized; therefore, it remains unclear whether the microbiota profile of these patients are distinct in composition, abundance, or diversity. To address this uncertainty, we employed 16S rRNA gene profiling to characterize the fecal microbiota in 14 stool samples among laboratory-confirmed and non-confirmed infant botulism cases. Seven bacterial phyla were identified among all 14 infant stool samples examined. Compared to samples from non-confirmed cases, the fecal microbiota of infant botulism patients displayed significantly higher Proteobacteria abundance. Of the 20 bacterial families identified, Enterobacteriaceae was significantly more abundant in samples from infants with botulism. Firmicutes abundance and the abundance ratio of Firmicutes/Proteobacteria was significantly lower in samples from infants with botulism. Lactobacillus spp. abundance was notably reduced in 12 of the 14 samples. Clostridium botulinum and Clostridium baratii were identified in low relative abundances in confirmed and non-confirmed samples based on their 16S rRNA gene profiles, although their toxigenicity remained undetermined. No significant differences were observed in the number of operational taxonomic units (OTUs) observed or in fecal microbiota diversity between laboratory-confirmed and non-confirmed samples. Correlations between individual phylum abundances and infant age were variable, and no significant differences were shown in number of OTUs observed or in fecal microbiota diversity between samples delineated by overall mean age. Significant differences in Proteobacteria, Firmicutes, and Enterobacteriaceae

What nurses need to know about fecal microbiota transplantation: education, assessment, and care for children and young adults.

PubMed

Samuel, Bennett P; Crumb, Teri L; Duba, Mary M

2014-01-01

Fecal microbiota transplantation (FMT) is an emerging experimental therapy for treatment of recurrent Clostridium difficile infection. In the future, FMT has the potential to be a treatment modality in other diseases that involve gut dysbiosis. As use of FMT is likely to expand, pediatric nurses need a clear understanding of FMT to provide appropriate education, assessment, and care for these patients. Pediatric research and clinical nurses are a resource to help children and parents understand the procedure. Important topics include donor screening, patient assessment before, during, and after treatment; routes of administration and positioning; preparation for discharge and followup evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach

PubMed Central

Fischer, Monika; Phelps, Emmalee; Rogers, Nicholas; Sagi, Sashidhar; Bohm, Matthew; Xu, Huiping; Kassam, Zain

2017-01-01

ABSTRACT Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients. PMID:28001467

Gut microbiota of liver transplantation recipients.

PubMed

Sun, Li-Ying; Yang, Yun-Sheng; Qu, Wei; Zhu, Zhi-Jun; Wei, Lin; Ye, Zhi-Sheng; Zhang, Jian-Rui; Sun, Xiao-Ye; Zeng, Zhi-Gui

2017-06-19

The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.

Does the Internet promote the unregulated use of fecal microbiota transplantation: a potential public health issue?

PubMed

Segal, Jonathan Philip; Abbasi, Faisal; Kanagasundaram, Cynthia; Hart, Ailsa

2018-01-01

The Internet has become an increasingly popular resource for medical information. Fecal microbiota transplantation (FMT) has changed the treatment of Clostridium difficile with cure rates of 81% following one infusion of FMT, further studies have since validated these findings. The Medicines and Health care Products Regulatory Agency has classified FMT as a medicine and hence should be only utilized in strict clinical settings. We searched Facebook, Twitter, Google, and YouTube using the words "Faecal Microbiota Transplantation" and "FMT". We utilized the first 50 hits on each site. We analyzed the percentage of articles that fell outside regulated medical practice. We searched how many clinics in the UK advertised practice that falls outside suggested guidelines. Google, YouTube, and Facebook had a variety of information regarding FMT available. Nine out of 50 (18%) of the top 50 google searches can be considered articles that fall outside regulated practice. YouTube highlighted four videos describing how to self-administer FMT, one of these was for ulcerative colitis. Fourteen percent of the top 50 YouTube videos fall outside regulated practice and 8% of the top 50 Facebook searches fall outside regulated clinical practice. There were two clinics in the UK advertising FMT for uses that fall outside regulated practice. Clinicians and patients need to be aware of the resources available through social media and the Internet. It should be appreciated that some websites fall outside regulated clinical practice. Private clinics offering FMT need to ensure that they are offering FMT within a regulated framework.

Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial.

PubMed

Bajaj, Jasmohan S; Kassam, Zain; Fagan, Andrew; Gavis, Edith A; Liu, Eric; Cox, I Jane; Kheradman, Raffi; Heuman, Douglas; Wang, Jessica; Gurry, Thomas; Williams, Roger; Sikaroodi, Masoumeh; Fuchs, Michael; Alm, Eric; John, Binu; Thacker, Leroy R; Riva, Antonio; Smith, Mark; Taylor-Robinson, Simon D; Gillevet, Patrick M

2017-12-01

Recurrent hepatic encephalopathy (HE) is a leading cause of readmission despite standard of care (SOC) associated with microbial dysbiosis. Fecal microbiota transplantation (FMT) may improve dysbiosis; however, it has not been studied in HE. We aimed to define whether FMT using a rationally derived stool donor is safe in recurrent HE compared to SOC alone. An open-label, randomized clinical trial with a 5-month follow-up in outpatient men with cirrhosis with recurrent HE on SOC was conducted with 1:1 randomization. FMT-randomized patients received 5 days of broad-spectrum antibiotic pretreatment, then a single FMT enema from the same donor with the optimal microbiota deficient in HE. Follow-up occurred on days 5, 6, 12, 35, and 150 postrandomization. The primary outcome was safety of FMT compared to SOC using FMT-related serious adverse events (SAEs). Secondary outcomes were adverse events, cognition, microbiota, and metabolomic changes. Participants in both arms were similar on all baseline criteria and were followed until study end. FMT with antibiotic pretreatment was well tolerated. Eight (80%) SOC participants had a total of 11 SAEs compared to 2 (20%) FMT participants with SAEs (both FMT unrelated; P = 0.02). Five SOC and no FMT participants developed further HE (P = 0.03). Cognition improved in the FMT, but not the SOC, group. Model for End-Stage Liver Disease (MELD) score transiently worsened postantibiotics, but reverted to baseline post-FMT. Postantibiotics, beneficial taxa, and microbial diversity reduction occurred with Proteobacteria expansion. However, FMT increased diversity and beneficial taxa. SOC microbiota and MELD score remained similar throughout. FMT from a rationally selected donor reduced hospitalizations, improved cognition, and dysbiosis in cirrhosis with recurrent HE. (Hepatology 2017;66:1727-1738). © 2017 by the American Association for the Study of Liver Diseases.

Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory bowel disease.

PubMed

Zhang, Ting; Xiang, Jie; Cui, Bota; He, Zhi; Li, Pan; Chen, Hai; Xu, Lijuan; Ji, Guozhong; Nie, Yongzhan; Wu, Kaichun; Fan, Daiming; Huang, Guangming; Bai, Jianling; Zhang, Faming

2017-10-24

There is a lack of health economics evidence on the use of fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD). This study aims to evaluate the cost-effectiveness before (with conventional therapy) and after introducing FMT for treating IBD. 104 patients with IBD received FMT were recruited. Health status was evaluated by European dimension health table (ED-5Q). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB) were calculated by different age groups, genders, smoking status, and disease subtypes. The willingness-to-pay threshold was set to the value equal to three times China's per capita GDP (141240 CNY/QALY, 2014). From the health-care perspective, FMT strategy was 73% likely to be cost-effective compared with the conventional therapy before FMT with an ICER of -185712 CNY/QALY and a positive NB of CNY 45150. From the societal perspective, FMT strategy was 75% likely to be cost-effective with an ICER of -207417 CNY/QALY and a positive NB of CNY 48395. Moreover, younger patients (≤ 24), females, non-smokers and Crohn's disease (CD) achieved more benefits. This study for the first time demonstrated that FMT showed its cost-effectiveness, especially on improving the life quality and decreasing the medical and societal cost, for the moderate to severe IBD in a Chinese cohort.

Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory bowel disease

PubMed Central

Zhang, Ting; Xiang, Jie; Cui, Bota; He, Zhi; Li, Pan; Chen, Hai; Xu, Lijuan; Ji, Guozhong; Nie, Yongzhan; Wu, Kaichun; Fan, Daiming; Huang, Guangming; Bai, Jianling; Zhang, Faming

2017-01-01

There is a lack of health economics evidence on the use of fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD). This study aims to evaluate the cost-effectiveness before (with conventional therapy) and after introducing FMT for treating IBD. 104 patients with IBD received FMT were recruited. Health status was evaluated by European dimension health table (ED-5Q). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB) were calculated by different age groups, genders, smoking status, and disease subtypes. The willingness-to-pay threshold was set to the value equal to three times China’s per capita GDP (141240 CNY/QALY, 2014). From the health-care perspective, FMT strategy was 73% likely to be cost-effective compared with the conventional therapy before FMT with an ICER of -185712 CNY/QALY and a positive NB of CNY 45150. From the societal perspective, FMT strategy was 75% likely to be cost-effective with an ICER of -207417 CNY/QALY and a positive NB of CNY 48395. Moreover, younger patients (≤ 24), females, non-smokers and Crohn’s disease (CD) achieved more benefits. This study for the first time demonstrated that FMT showed its cost-effectiveness, especially on improving the life quality and decreasing the medical and societal cost, for the moderate to severe IBD in a Chinese cohort. PMID:29179485

Gut microbiota composition modifies fecal metabolic profiles in mice.

PubMed

Zhao, Ying; Wu, Junfang; Li, Jia V; Zhou, Ning-Yi; Tang, Huiru; Wang, Yulan

2013-06-07

The gut microbiome is known to be extensively involved in human health and disease. In order to reveal the metabolic relationship between host and microbiome, we monitored recovery of the gut microbiota composition and fecal profiles of mice after gentamicin and/or ceftriaxone treatments. This was performed by employing (1)H nuclear magnetic resonance (NMR)-based metabonomics and denaturing gradient gel electrophoresis (DGGE) fingerprint of gut microbiota. The common features of fecal metabolites postantibiotic treatment include decreased levels of short chain fatty acids (SCFAs), amino acids and primary bile acids and increased oligosaccharides, d-pinitol, choline and secondary bile acids (deoxycholic acid). This suggests suppressed bacterial fermentation, protein degradation and enhanced gut microbial modification of bile acids. Barnesiella, Prevotella, and Alistipes levels were shown to decrease as a result of the antibiotic treatment, whereas levels of Bacteroides, Enterococcus and Erysipelotrichaceae incertae sedis, and Mycoplasma increased after gentamicin and ceftriaxone treatment. In addition, there was a strong correlation between fecal profiles and levels of Bacteroides, Barnesiella, Alistipes and Prevotella. The integration of metabonomics and gut microbiota profiling provides important information on the changes of gut microbiota and their impact on fecal profiles during the recovery after antibiotic treatment. The correlation between gut microbiota and fecal metabolites provides important information on the function of bacteria, which in turn could be important in optimizing therapeutic strategies, and developing potential microbiota-based disease preventions and therapeutic interventions.

Household siblings and nasal and fecal microbiota in infants.

PubMed

Hasegawa, Kohei; Linnemann, Rachel W; Mansbach, Jonathan M; Ajami, Nadim J; Espinola, Janice A; Fiechtner, Lauren G; Petrosino, Joseph F; Camargo, Carlos A

2017-04-01

Early-life exposure to older siblings is associated with a lower risk of asthma. To date, no study has addressed the impact of having siblings on both the airway and fecal microbiota during infancy. The aim of this study was therefore to profile the nasal airway and fecal microbiota in infants, and to examine the association between having siblings and microbiota profile. We conducted a cross-sectional study of 105 healthy infants (aged <1 year). Using 16S rRNA gene sequencing and an unbiased clustering approach to the nasal airway and fecal samples, we identified microbiota profiles and then determined the association between having siblings and microbiome profile. Overall, the median age was 3.4 months (IQR, 2.0-4.7 months); 43% had siblings in the household. Unbiased clustering of nasal airway microbiota identified three profiles: Moraxella dominant (43%), Corynebacterium/Dolosigranulum dominant (36%), and mixed (21%). Infants with siblings were more likely to have a Moraxella-dominant profile than Corynebacterium/Dolosigranulum-dominant profile (76% vs 18%), while those without siblings had the opposite pattern (18% vs 50%; P < 0.001, multivariable-adjusted). Fecal microbiota consisted of three profiles: Bifidobacterium dominant (39%), Escherichia dominant (31%), and Enterobacter dominant (30%). Infants with siblings were more likely to have a Bifidobacterium-dominant profile than Escherichia-dominant profile (49% vs 24%) while those without siblings had the opposite pattern (32% vs 37%; P = 0.04, multivariable-adjusted). In this cross-sectional study, infants with siblings were more likely to have a Moraxella-dominant nasal microbiota profile and Bifidobacterium-dominant fecal microbiota profile. These findings should facilitate further investigation of the interplay between early-life environmental exposure, the microbiome, and childhood asthma. © 2016 Japan Pediatric Society.

Alteration of the fecal microbiota in Chinese patients with Parkinson's disease.

PubMed

Qian, Yiwei; Yang, Xiaodong; Xu, Shaoqing; Wu, Chunyan; Song, Yanyan; Qin, Nan; Chen, Sheng-Di; Xiao, Qin

2018-05-01

Emerging evidences suggest that gut microbiota dysbiosis plays a role in Parkinson's disease (PD). However, the alterations in fecal microbiome in Chinese PD patients remains unknown. This case-control study was conducted to explore fecal microbiota compositions in Chinese PD patients. Microbiota communities in the feces of 45 patients and their healthy spouses were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between fecal microbiota and PD clinical characteristics were analyzed. The structure and richness of the fecal microbiota differed between PD patients and healthy controls. Genera Clostridium IV, Aquabacterium, Holdemania, Sphingomonas, Clostridium XVIII, Butyricicoccus and Anaerotruncus were enriched in the feces of PD patients after adjusting for age, gender, body mass index (BMI), and constipation. Furthermore, genera Escherichia/Shigella were negatively associated with disease duration. Genera Dorea and Phascolarctobacterium were negatively associated with levodopa equivalent doses (LED). Among the non-motor symptoms (NMSs), genera Butyricicoccus and Clostridium XlVb were associated with cognitive impairment. Overall, we confirmed that gut microbiota dysbiosis occurs in Chinese patients with PD. A well-controlled population involved was beneficial for the identification of microbiota associated with diseases. Additionally, the fecal microbiota was closely related to PD clinical characteristics. Elucidating these differences in the fecal microbiome will provide a foundation to improve our understanding the pathogenesis of PD and to support the potentially therapeutic options modifying the gut microbiota. Copyright © 2018 Elsevier Inc. All rights reserved.

Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis

PubMed Central

Sun, Dali; Li, Weiming; Li, Shumin; Cen, Yunyun; Xu, Qingwen; Li, Yijun; Sun, Yanbo; Qi, Yuxing; Lin, Yueying; Yang, Ting; Xu, Pengyuan; Lu, Qiping

2016-01-01

Abstract Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC. A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome. Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6–39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I2 = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events. FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT. PMID:27281075

Transplantation of human microbiota into conventional mice durably reshapes the gut microbiota.

PubMed

Wrzosek, Laura; Ciocan, Dragos; Borentain, Patrick; Spatz, Madeleine; Puchois, Virginie; Hugot, Cindy; Ferrere, Gladys; Mayeur, Camille; Perlemuter, Gabriel; Cassard, Anne-Marie

2018-05-01

Human microbiota-associated (HMA) mice are an important model to study the relationship between liver diseases and intestinal microbiota. We describe a new method to humanize conventional mice based on bowel cleansing with polyethylene glycol followed by fecal microbiota transplantation (FMT) from a human donor. Four successive bowel cleansings were sufficient to empty the intestine and decrease the microbiota by 90%. We then compared four different strategies based on the frequency of FMT over four weeks: (1) twice a week; (2) once a week; (3) two FMTs; (4) one FMT. We were able to transfer human bacteria to mice, irrespective of the strategy used. We detected human bacteria after four weeks, even if only one FMT was performed, but there was a shift of the microbiota over time. FMT twice a week for four weeks was too frequent and perturbed the stability of the newly formed ecosystem. FMT once a week appears to be the best compromise as it allowed engraftment of Faecalibacterium, and a higher diversity of bacteria belonging to the Bacteroidales order. Our easy to establish HMA mouse model could be used as an alternative to classical HMA mice to study the relationship between the liver and the microbiota.

Antibiotic treatment induces long-lasting changes in the fecal microbiota that protect against colitis

PubMed Central

Ward, Naomi L.; Phillips, Caleb D.; Nguyen, Deanna D.; Shanmugam, Nanda Kumar N.; Song, Yan; Hodin, Richard; Shi, Hai Ning; Cherayil, Bobby J.; Goldstein, Allan M.

2017-01-01

Background The interplay between host genetics, immunity, and microbiota is central to the pathogenesis of inflammatory bowel disease (IBD). Previous population-based studies suggested a link between antibiotic use and increased IBD risk, but the mechanisms are unknown. The purpose of this study was to determine the long-term effects of antibiotic administration on microbiota composition, innate immunity, and susceptibility to colitis, as well as the mechanism by which antibiotics alter host colitogenicity. Methods Wild-type mice were given broad-spectrum antibiotics or no antibiotics for two weeks, and subsequent immunophenotyping and 16S rRNA gene sequencing-based analysis of the fecal microbiome were performed six weeks later. In a separate experiment, control and antibiotic-treated mice were given seven days of DSS, six weeks after completing antibiotic treatment, and the severity of colitis scored histologically. Fecal transfer was performed from control or antibiotic-treated mice to recipient mice whose endogenous microbiota had been cleared with antibiotics, and the susceptibility of the recipients to DSS-induced colitis was analyzed. Naïve CD4+ T cells were transferred from control and antibiotic-treated mice to immunodeficient Rag-1-/- recipients and the severity of colitis compared. Results Antibiotics led to sustained dysbiosis and changes in T-cell subpopulations, including reductions in colonic lamina propria total T cells and CD4+ T cells. Antibiotics conferred protection against DSS colitis, and this effect was transferable by fecal transplant but not by naïve T cells. Conclusions Antibiotic exposure protects against colitis, and this effect is transferable with fecal microbiota from antibiotic-treated mice, supporting a protective effect of the microbial community. PMID:27607336

Gut Microbiota and Tacrolimus Dosing in Kidney Transplantation

PubMed Central

Lee, John R.; Muthukumar, Thangamani; Dadhania, Darshana; Taur, Ying; Jenq, Robert R.; Toussaint, Nora C.; Ling, Lilan; Pamer, Eric; Suthanthiran, Manikkam

2015-01-01

Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2±1.1 mg/day vs. 3.8±0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6±2.4 mg/day vs. 3.3±1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient±standard error of 1.0±0.6 (P=0.08) after multivariable linear regression. Our novel

Fecal transplant policy and legislation

PubMed Central

Vyas, Dinesh; Aekka, Apoorva; Vyas, Arpita

2015-01-01

Fecal microbiota transplantation (FMT) has garnered significant attention in recent years in the face of a reemerging Clostridium difficile (C. difficile) epidemic. Positive results from the first randomized control trial evaluating FMT have encouraged the medical community to explore the process further and expand its application beyond C. difficile infections and even the gastrointestinal domain. However promising and numerous the prospects of FMT appear, the method remains limited in scope today due to several important barriers, most notably a poorly defined federal regulatory policy. The Food and Drug Administration has found it difficult to standardize and regulate the administration of inherently variable, metabolically active, and ubiquitously available fecal material. The current cumbersome policy, which classifies human feces as a drug, has prevented physicians from providing FMT and deserving patients from accessing FMT in a timely fashion, and subsequent modifications seem only to be temporary. The argument for reclassifying fecal material as human tissue is well supported. Essentially, this would allow for a regulatory framework that is sufficiently flexible to expand access to care and facilitate research, but also appropriately restrictive and centralized to ensure patient safety. Such an approach can facilitate the advancement of FMT to a more refined, controlled, and aesthetic process, perhaps in the form of a customized and well-characterized stool substitute therapy. PMID:25574076

Gut microbiota and allogeneic transplantation.

PubMed

Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

2015-08-23

The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

Coordinated Hospital-Home Fecal Microbiota Transplantation via Percutaneous Endoscopic Cecostomy for Recurrent Steroid-Dependent Ulcerative Colitis.

PubMed

Ni, Xiaodong; Fan, Shengxian; Zhang, Yongliang; Wang, Zhiming; Ding, Lan; Li, Yousheng; Li, Jieshou

2016-11-15

Since its introduction as an alternative intestinal microbiota alteration approach, fecal microbiota transplantation (FMT) has been increasingly used as a treatment of choice for patients with ulcerative colitis (UC), but no reports exist regarding FMT via percutaneous endoscopic cecostomy (PEC). This report describes the case of a 24-year-old man with a 7-year history of recurrent, steroid-dependent UC. He received FMT via PEC once per day for 1 month in the hospital. After the remission of gastrointestinal symptoms, he was discharged from the hospital and continued FMT via PEC twice per week for 3 months at home. The frequency of stools decreased, and the characteristics of stools improved soon thereafter. Enteral nutrition was regained after 1 week, and an oral diet was begun 1 month later. Two months after the FMT end point, the patient resumed a normal diet, with formed soft stools once per day. The follow-up colonoscopy showed normal mucus membranes; then, the PEC set was removed. On the subsequent 12 months follow-up, the patient resumed orthobiosis without any gastrointestinal discomfort and returned to work. This case emphasizes that FMT via PEC can not only induce remission but also shorten the duration of hospitalization and reduce the medical costs; therefore, this approach should be considered an alternative option for patients with UC.

The Fecal Microbiota Profile and Bronchiolitis in Infants

PubMed Central

Linnemann, Rachel W.; Mansbach, Jonathan M.; Ajami, Nadim J.; Espinola, Janice A.; Petrosino, Joseph F.; Piedra, Pedro A.; Stevenson, Michelle D.; Sullivan, Ashley F.; Thompson, Amy D.; Camargo, Carlos A.

2016-01-01

BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case–control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58–15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56–12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case–control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis. PMID:27354456

Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.

PubMed

Woodworth, Michael H; Kraft, Colleen S; Meredith, Erika J; Mehta, Aneesh K; Wang, Tiffany; Mamo, Yafet T; Dhere, Tanvi; Sitchenko, Kaitlin L; Patzer, Rachel E; Friedman-Moraco, Rachel J

2018-04-01

Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Core fecal microbiota of domesticated herbivorous ruminant, hindgut fermenters, and monogastric animals.

PubMed

O' Donnell, Michelle M; Harris, Hugh M B; Ross, R Paul; O'Toole, Paul W

2017-10-01

In this pilot study, we determined the core fecal microbiota composition and overall microbiota diversity of domesticated herbivorous animals of three digestion types: hindgut fermenters, ruminants, and monogastrics. The 42 animals representing 10 animal species were housed on a single farm in Ireland and all the large herbivores consumed similar feed, harmonizing two of the environmental factors that influence the microbiota. Similar to other mammals, the fecal microbiota of all these animals was dominated by the Firmicutes and Bacteroidetes phyla. The fecal microbiota spanning all digestion types comprised 42% of the genera identified. Host phylogeny and, to a lesser extent, digestion type determined the microbiota diversity in these domesticated herbivores. This pilot study forms a platform for future studies into the microbiota of nonbovine and nonequine domesticated herbivorous animals. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation.

PubMed

Broecker, Felix; Klumpp, Jochen; Schuppler, Markus; Russo, Giancarlo; Biedermann, Luc; Hombach, Michael; Rogler, Gerhard; Moelling, Karin

2016-01-01

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients' gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.5 yr post-FMT compared with the stool donor. Feces were subjected to DNA sequencing to characterize bacteria and double-stranded DNA (dsDNA) viruses including phages. The patient's microbial communities varied over time and showed little overall similarity to the donor until 7 mo post-FMT, indicating ongoing gut microbiota adaption in this time period. After 4.5 yr, the patient's bacteria attained donor-like compositions at phylum, class, and order levels with similar bacterial diversity. Differences in the bacterial communities between donor and patient after 4.5 yr were seen at lower taxonomic levels. C. difficile remained undetectable throughout the entire timespan. This demonstrated sustainable donor feces engraftment and verified long-term therapeutic success of FMT on the molecular level. Full engraftment apparently required longer than previously acknowledged, suggesting the implementation of year-long patient follow-up periods into clinical practice. The identified dsDNA viruses were mainly Caudovirales phages. Unexpectedly, sequences related to giant algae-infecting Chlorella viruses were also detected. Our findings indicate that intestinal viruses may be implicated in the establishment of gut microbiota. Therefore, virome analyses should be included in gut microbiota studies to determine the roles of phages and other viruses-such as Chlorella viruses-in human health and disease, particularly during RCDI.

Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment.

PubMed

2016-01-01

Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians' perception of patients' lived experience, and a modified grounded theory method to analyze information from the survey. For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85-5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14-3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46-212.44; abdominal cramping, relative risk 14.81, 95% CI 2.07-105.97) (GRADE: low). For

Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of Recurrent Clostridium Difficile Infection: A Literature Review.

PubMed

Arbel, Leor T; Hsu, Edmund; McNally, Keegan

2017-08-23

Clostridium difficile ( C. difficile ) is a common cause of antibiotic--associated diarrhea (AAD), being responsible for 15--25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management.

Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics

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

Lee, Sonny T. M.; Kahn, Stacy A.; Delmont, Tom O.

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits. Here, we used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track themore » occurrence and distribution patterns of donor MAGs in two FMT recipients. Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8 weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems. Lastly, the analytical strategy adopted in our study can provide genomic insights

Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics

DOE PAGES

Lee, Sonny T. M.; Kahn, Stacy A.; Delmont, Tom O.; ...

2017-05-04

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits. Here, we used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track themore » occurrence and distribution patterns of donor MAGs in two FMT recipients. Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8 weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems. Lastly, the analytical strategy adopted in our study can provide genomic insights

Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment

PubMed Central

2016-01-01

Background Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). Methods We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians’ perception of patients’ lived experience, and a modified grounded theory method to analyze information from the survey. Results For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85–5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14–3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46–212.44; abdominal cramping, relative risk 14

Fecal microbiota variation across the lifespan of the healthy laboratory rat.

PubMed

Flemer, Burkhardt; Gaci, Nadia; Borrel, Guillaume; Sanderson, Ian R; Chaudhary, Prem P; Tottey, William; O'Toole, Paul W; Brugère, Jean-François

2017-09-03

Laboratory rats are commonly used in life science research as a model for human biology and disease, but the composition and development of their gut microbiota during life is poorly understood. We determined the fecal microbiota composition of healthy Sprague Dawley laboratory rats from 3 weeks to 2 y of age, kept under controlled environmental and dietary conditions. Additionally, we determined fecal short-chain fatty acid profiles, and we compared the rat fecal microbiota with that of mice and humans. Gut microbiota and to a lesser extent SCFAs profiles separated rats into 3 different clusters according to age: before weaning, first year of life (12- to 26-week-old animals) and second year of life (52- to 104-week-old). A core of 46 bacterial species was present in all rats but its members' relative abundance progressively decreased with age. This was accompanied by an increase of microbiota α-diversity, likely due to the acquisition of environmental microorganisms during the lifespan. Contrastingly, the functional profile of the microbiota across animal species became more similar upon aging. Lastly, the microbiota of rats and mice were most similar to each other but at the same time the microbiota profile of rats was more similar to that of humans than was the microbiota profile of mice. These data offer an explanation as to why germ-free rats are more efficient recipients and retainers of human microbiota than mice. Furthermore, experimental design should take into account dynamic changes in the microbiota of model animals considering that their changing gut microbiota interacts with their physiology.

Effect of Aging on the Composition of Fecal Microbiota in Donors for FMT and Its Impact on Clinical Outcomes.

PubMed

Anand, Rohit; Song, Yang; Garg, Shashank; Girotra, Mohit; Sinha, Amitasha; Sivaraman, Anita; Phillips, Laila; Dutta, Sudhir K

2017-04-01

Fecal microbiota transplantation (FMT) is emerging as an effective therapy for the treatment of recurrent Clostridium difficile infection (RCDI). Selecting an appropriate donor is vital to the success of FMT. However, the relationship between age of donors and the efficacy of FMT has not been examined to date. The aim of this study was to examine the effect of age of healthy donors on their fecal microbiota and assess the impact of these changes on the clinical efficacy of FMT. This IRB-approved prospective study enrolled donors who were deemed healthy for FMT after careful detailed screening for infectious diseases per institutional protocol. The study was conducted between January 2011 and October 2014. Fecal samples were processed and analyzed using 16S rRNA gene amplicon sequencing. Differences in relative abundance and diversity of the donor fecal microbiota were analyzed in donors above and below 60 years of age. Effect of fecal microbiota from donors of different age groups on the efficacy of FMT was also evaluated. Twenty-eight healthy human subjects from ages 20-82 years were enrolled as donors for FMT. All patients receiving FMT from their respective donors had resolution of RCDI symptoms and had a negative C. difficile toxin test 4-12 weeks after FMT. Genomic analysis showed that the relative abundance of phylum Actinobacteria and family Bifidobacteriaceae was reduced in the donors ≥60 years of age (p < 0.05). However, Bacteroidetes-to-Fermicutes ratio did not demonstrate a significant change between the two groups. Furthermore, microbial diversity did not change significantly with advancing age. These observations suggest that aging in healthy donors is associated with compositional alterations in the fecal microbiome without change in the overall microbial diversity. These changes do not seem to affect the clinical efficacy of FMT in RCDI patients over 12 months.

Fecal Microbiota Transplantation as Therapy for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

PubMed Central

Colman, Ruben J.; Rubin, David T.

2014-01-01

Background and aims Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD. Methods A systematic literature search was performed through May 2014. Inclusion criteria required FMT as primary therapeutic agent. Clinical remission (CR) and/or mucosal healing were defined as primary outcomes. Studies were excluded if they did not report clinical outcomes or included patients with infections. Results Eighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included in the analysis. 122 patients were described (79 ulcerative colitis (UC); 39 Crohn's disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow up. Among cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%-60.4%), with a moderate risk of heterogeneity (Cochran's Q, P=0.011; I2 = 37%). Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4%-40.8%) for UC (Cochran's Q, P=0.37; I2 =0%) and 60.5% (95% CI 28.4%-85.6%) for CD (Cochran's Q, P=0.05; I2 = 37%). Six studies performed microbiota analysis. Conclusions This analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis. PMID:25223604

Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection.

PubMed

Varier, Raghu U; Biltaji, Eman; Smith, Kenneth J; Roberts, Mark S; Kyle Jensen, M; LaFleur, Joanne; Nelson, Richard E

2015-04-01

Clostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA. We constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed. Base-case analysis showed that FMT was less costly ($1,669 vs $3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were ≥70% and <91%, respectively, and if the cost of FMT was <$3,206. Probabilistic sensitivity analysis, varying all parameters simultaneously, showed that FMT was the dominant strategy over 10, 000 second-order Monte Carlo simulations. Our results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.

GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis.

PubMed

Brittnacher, Mitchell J; Heltshe, Sonya L; Hayden, Hillary S; Radey, Matthew C; Weiss, Eli J; Damman, Christopher J; Zisman, Timothy L; Suskind, David L; Miller, Samuel I

2016-01-01

Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking. We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray-Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT. Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes

Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of Recurrent Clostridium Difficile Infection: A Literature Review

PubMed Central

Arbel, Leor T; McNally, Keegan

2017-01-01

Clostridium difficile (C. difficile) is a common cause of antibiotic-­associated diarrhea (AAD), being responsible for 15­-25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management. PMID:29067223

16S rDNA analysis of the effect of fecal microbiota transplantation on pulmonary and intestinal flora.

PubMed

Liu, Tianhao; Yang, Zhongshan; Zhang, Xiaomei; Han, Niping; Yuan, Jiali; Cheng, Yu

2017-12-01

This study aims to explore the effect of FMT on regulations of dysbacteriosis of pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups: normal control group (K), model control group (MX), and fecal microbiota transplantation group (FMT); each group contained nine rats. The OTU values of the pulmonary and intestinal flora of the MX group decreased significantly compared with the normal control group. After FMT, the OTU value of pulmonary flora increased, while the value of OTU in intestinal flora declined. At the phylum level, FMT down-regulated Proteobacteria , Firmicutes , and Bacteroidetes in the pulmonary flora. At the genus level, FMT down-regulated Pseudomonas , Sphingobium , Lactobacillus , Rhizobium , and Acinetobacter , thus maintaining the balance of the pulmonary flora. Moreover, FMT could change the structure and diversity of the pulmonary and intestinal flora by positively regulating the pulmonary flora and negatively regulating intestinal flora. This study may provide a scientific basis for FMT treatment of respiratory diseases.

The Present Status of Fecal Microbiota Transplantation and Its Value in the Elderly.

PubMed

Cheng, Yao-Wen; Fischer, Monika

2017-09-01

PURPOSE OF REVIEW: This article will review current literature describing fecal microbiota transplantation (FMT) in the treatment of various diseases, and its potential role in elderly patients (age ≥ 65 years). Research on FMT has blossomed in the last decade and its pivotal role in the treatment of recurrent Clostridium difficile infection (CDI) has been recognized by the American College of Gastroenterology in the latest guidelines. There is also emerging evidence that FMT may be beneficial in the treatment of severe and/or complicated CDI refractory to medical therapy, resulting in decreased rates of colectomy and mortality. In the elderly, CDI is associated with markedly higher rates of mortality and colectomy; outcomes are even worse when patients have underlying inflammatory bowel disease (IBD). While the majority of patients who receive FMT for CDI are older, only a handful of studies focused specifically on FMT treatment outcomes and safety in this age group. Current data corroborate the efficacy and safety profile of FMT, while also supporting its use for recurrent, severe, and/or complicated CDI in the elderly population. FMT is recommended for the treatment of recurrent, severe, and/or complicated CDI in patients older than 65 years of age. It may be prudent to offer FMT earlier in the disease course, possibly after just the second recurrence and for the first episode of severe CDI to avert complications including colectomy and end-organ failure that elderly patients are more prone to developing.

Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease.

PubMed

Khanna, Sahil; Vazquez-Baeza, Yoshiki; González, Antonio; Weiss, Sophie; Schmidt, Bradley; Muñiz-Pedrogo, David A; Rainey, John F; Kammer, Patricia; Nelson, Heidi; Sadowsky, Michael; Khoruts, Alexander; Farrugia, Stefan L; Knight, Rob; Pardi, Darrell S; Kashyap, Purna C

2017-05-15

Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD. There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD. FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.

Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation.

PubMed

Sokol, Harry; Galperine, Tatiana; Kapel, Nathalie; Bourlioux, Pierre; Seksik, Philippe; Barbut, Frederic; Scanzi, Julien; Chast, François; Batista, Rui; Joly, Francisca; Joly, Anne-Christine; Collignon, Anne; Guery, Benoit; Beaugerie, Laurent

2016-03-01

Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Evaluation of Fecal Microbiota Transfer as Treatment for Postweaning Diarrhea in Research-Colony Puppies.

PubMed

Burton, Erin N; O'Connor, Erin; Ericsson, Aaron C; Franklin, Craig L

2016-01-01

Frequently just prior to or at weaning (approximate age, 6 to 8 wk), puppies in research settings often develop diarrheal disease, which may be due, in part, to an immature and unstable intestinal microbiota that is permissive to opportunistic pathogens. The overall objective of this study was to assess whether fecal microbiota transfer (FMT) increased the transmission of a stable maternal microbiota to pups and decreased the incidence of postweaning diarrhea. Puppies were designated by litter as treated (FMT) or sham-treated. The FMT group received fecal inoculum orally for 5 consecutive days during weaning (at 6 to 8 wk of age). Diarrhea was evaluated according to a published scoring system for 11 d during the weaning period. Fresh feces were collected from dams and puppies at 3 d before weaning and 3, 10, and 24 d after weaning for analysis of the fecal microbiota by using 16S rRNA amplicon sequencing. The composition of fecal inoculum refrigerated at 3 to 5 °C was stable for at least 5 d. No diarrhea was reported in either group during the study period, making comparison of treated and control groups problematic. However, 16S rRNA gene analysis revealed microbial variability across time in both groups. Therefore, although the fecal microbiota of neither group of puppies mirrored the dam at any of the designated time points, the data provided fundamental and novel information regarding the dynamic maturation process of the fecal microbiota of puppies after weaning.

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis

PubMed Central

Grewal, Suman; LaComb, Joseph F.; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M.; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E.; Frank, Daniel N.; Li, Ellen

2018-01-01

Background Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). Method V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Results Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

PubMed

Mintz, Michael; Khair, Shanawaj; Grewal, Suman; LaComb, Joseph F; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E; Frank, Daniel N; Li, Ellen

2018-01-01

Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes

Characterization of the fecal microbiota using high-throughput sequencing reveals a stable microbial community during storage.

PubMed

Carroll, Ian M; Ringel-Kulka, Tamar; Siddle, Jennica P; Klaenhammer, Todd R; Ringel, Yehuda

2012-01-01

The handling and treatment of biological samples is critical when characterizing the composition of the intestinal microbiota between different ecological niches or diseases. Specifically, exposure of fecal samples to room temperature or long term storage in deep freezing conditions may alter the composition of the microbiota. Thus, we stored fecal samples at room temperature and monitored the stability of the microbiota over twenty four hours. We also investigated the stability of the microbiota in fecal samples during a six month storage period at -80°C. As the stability of the fecal microbiota may be affected by intestinal disease, we analyzed two healthy controls and two patients with irritable bowel syndrome (IBS). We used high-throughput pyrosequencing of the 16S rRNA gene to characterize the microbiota in fecal samples stored at room temperature or -80°C at six and seven time points, respectively. The composition of microbial communities in IBS patients and healthy controls were determined and compared using the Quantitative Insights Into Microbial Ecology (QIIME) pipeline. The composition of the microbiota in fecal samples stored for different lengths of time at room temperature or -80°C clustered strongly based on the host each sample originated from. Our data demonstrates that fecal samples exposed to room or deep freezing temperatures for up to twenty four hours and six months, respectively, exhibit a microbial composition and diversity that shares more identity with its host of origin than any other sample.

Faecal microbiota transplant - prospects and safety.

PubMed

Bartnicka, Anna; Szachta, Patrycja; Gałecka, Mirosława

2015-01-01

The intestinal microbiota, either directly or indirectly, plays an important role in maintaining the homeostasis of the body. The intestine microorganisms are significant due to the role they play in stimulating the development of the immune system, protecting against pathogens, and also managing metabolic and nutrient processing. The effectiveness of probiotics and prebiotics in various gastrointestinal diseases has been repeatedly confirmed. However, increasing interest in faecal transplantation has also been observed. Its efficacy in the treatment of pseudomembranous colitis has been repeatedly demonstrated. More often this method is discussed regarding the possibility of using it in other diseases linked with dysbiosis. Faecal microbiota transplantation, because of its rapid efficacy, minimal risk and adverse effects, relatively low cost, and the ability to re-establish the correct intestinal microbiota profile, could be an alternative treatment method in several other diseases. This paper will introduce the latest therapeutic aspects of microbiota transplantation, including its implications in the treatment of gastrointestinal diseases.

Toward an Understanding of Changes in Diversity Associated with Fecal Microbiome Transplantation Based on 16S rRNA Gene Deep Sequencing

PubMed Central

Shahinas, Dea; Silverman, Michael; Sittler, Taylor; Chiu, Charles; Kim, Peter; Allen-Vercoe, Emma; Weese, Scott; Wong, Andrew; Low, Donald E.; Pillai, Dylan R.

2012-01-01

ABSTRACT Fecal microbiome transplantation by low-volume enema is an effective, safe, and inexpensive alternative to antibiotic therapy for patients with chronic relapsing Clostridium difficile infection (CDI). We explored the microbial diversity of pre- and posttransplant stool specimens from CDI patients (n = 6) using deep sequencing of the 16S rRNA gene. While interindividual variability in microbiota change occurs with fecal transplantation and vancomycin exposure, in this pilot study we note that clinical cure of CDI is associated with an increase in diversity and richness. Genus- and species-level analysis may reveal a cocktail of microorganisms or products thereof that will ultimately be used as a probiotic to treat CDI. PMID:23093385

Association of dietary type with fecal microbiota in vegetarians and omnivores in Slovenia.

PubMed

Matijašić, Bojana Bogovič; Obermajer, Tanja; Lipoglavšek, Luka; Grabnar, Iztok; Avguštin, Gorazd; Rogelj, Irena

2014-06-01

The purpose of this study was to discover differences in the human fecal microbiota composition driven by long-term omnivore versus vegan/lacto-vegetarian dietary pattern. In addition, the possible association of demographic characteristics and dietary habits such as consumption of particular foods with the fecal microbiota was examined. This study was conducted on a Slovenian population comprising 31 vegetarian participants (11 lacto-vegetarians and 20 vegans) and 29 omnivore participants. Bacterial DNA was extracted from the frozen fecal samples by Maxwell 16 Tissue DNA Purification Kit (Promega). Relative quantification of selected bacterial groups was performed by real-time PCR. Differences in fecal microbiota composition were evaluated by PCR-DGGE fingerprinting of the V3 16S rRNA region. Participants' demographic characteristics, dietary habits and health status information were collected through a questionnaire. Vegetarian diet was associated with higher ratio (% of group-specific DNA in relation to all bacterial DNA) of Bacteroides-Prevotella, Bacteroides thetaiotaomicron, Clostridium clostridioforme and Faecalibacterium prausnitzii, but with lower ratio (%) of Clostridium cluster XIVa. Real-time PCR also showed a higher concentration and ratio of Enterobacteriaceae (16S rDNA copies/g and %) in female participants (p < 0.05 and p < 0.01) and decrease in Bifidobacterium with age (p < 0.01). DGGE analysis of the 16S rRNA V3 region showed that relative quantity of DGGE bands from certain bacterial groups was lower (Bifidobacterium, Streptococus, Collinsella and Lachnospiraceae) or higher (Subdoligranulum) among vegetarians, indicating the association of dietary type with bacterial community composition. Sequencing of selected DGGE bands revealed the presence of common representatives of fecal microbiota: Bacteroides, Eubacterium, Faecalibacterium, Ruminococcaceae, Bifidobacterium and Lachnospiraceae. Up to 4 % of variance in microbial community analyzed

Diet and Environment Shape Fecal Bacterial Microbiota Composition and Enteric Pathogen Load of Grizzly Bears

PubMed Central

Schwab, Clarissa; Cristescu, Bogdan; Northrup, Joseph M.; Stenhouse, Gordon B.; Gänzle, Michael

2011-01-01

Background Diet and environment impact the composition of mammalian intestinal microbiota; dietary or health disturbances trigger alterations in intestinal microbiota composition and render the host susceptible to enteric pathogens. To date no long term monitoring data exist on the fecal microbiota and pathogen load of carnivores either in natural environments or in captivity. This study investigates fecal microbiota composition and the presence of pathogenic Escherichia coli and toxigenic clostridia in wild and captive grizzly bears (Ursus arctos) and relates these to food resources consumed by bears. Methodology/Principal Findings Feces were obtained from animals of two wild populations and from two captive animals during an active bear season. Wild animals consumed a diverse diet composed of plant material, animal prey and insects. Captive animals were fed a regular granulated diet with a supplement of fruits and vegetables. Bacterial populations were analyzed using quantitative PCR. Fecal microbiota composition fluctuated in wild and in captive animals. The abundance of Clostridium clusters I and XI, and of C. perfringens correlated to regular diet protein intake. Enteroaggregative E. coli were consistently present in all populations. The C. sordellii phospholipase C was identified in three samples of wild animals and for the first time in Ursids. Conclusion This is the first longitudinal study monitoring the fecal microbiota of wild carnivores and comparing it to that of captive individuals of the same species. Location and diet affected fecal bacterial populations as well as the presence of enteric pathogens. PMID:22194798

Diet and environment shape fecal bacterial microbiota composition and enteric pathogen load of grizzly bears.

PubMed

Schwab, Clarissa; Cristescu, Bogdan; Northrup, Joseph M; Stenhouse, Gordon B; Gänzle, Michael

2011-01-01

Diet and environment impact the composition of mammalian intestinal microbiota; dietary or health disturbances trigger alterations in intestinal microbiota composition and render the host susceptible to enteric pathogens. To date no long term monitoring data exist on the fecal microbiota and pathogen load of carnivores either in natural environments or in captivity. This study investigates fecal microbiota composition and the presence of pathogenic Escherichia coli and toxigenic clostridia in wild and captive grizzly bears (Ursus arctos) and relates these to food resources consumed by bears. Feces were obtained from animals of two wild populations and from two captive animals during an active bear season. Wild animals consumed a diverse diet composed of plant material, animal prey and insects. Captive animals were fed a regular granulated diet with a supplement of fruits and vegetables. Bacterial populations were analyzed using quantitative PCR. Fecal microbiota composition fluctuated in wild and in captive animals. The abundance of Clostridium clusters I and XI, and of C. perfringens correlated to regular diet protein intake. Enteroaggregative E. coli were consistently present in all populations. The C. sordellii phospholipase C was identified in three samples of wild animals and for the first time in Ursids. This is the first longitudinal study monitoring the fecal microbiota of wild carnivores and comparing it to that of captive individuals of the same species. Location and diet affected fecal bacterial populations as well as the presence of enteric pathogens.

Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis.

PubMed

Jacob, Vinita; Crawford, Carl; Cohen-Mekelburg, Shirley; Viladomiu, Monica; Putzel, Gregory G; Schneider, Yecheskel; Chabouni, Fatiha; OʼNeil, Sarah; Bosworth, Brian; Woo, Viola; Ajami, Nadim J; Petrosino, Joseph F; Gerardin, Ylaine; Kassam, Zain; Smith, Mark; Iliev, Iliyan D; Sonnenberg, Gregory F; Artis, David; Scherl, Ellen; Longman, Randy S

2017-06-01

Recent trials suggest fecal microbiota transplantation (FMT) with repeated enemas and high-diversity FMT donors is a promising treatment to induce remission in ulcerative colitis. We designed a prospective, open-label pilot study to assess the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active ulcerative colitis using a 2-donor fecal microbiota preparation (FMP). Safety and clinical endpoints of response, remission, and mucosal healing at week 4 were assessed. Fecal DNA and rectal biopsies were used to characterize the microbiome and mucosal CD4 T cells, respectively, before and after FMT. Of the 20 patients enrolled in this study, 7 patients (35%) achieved a clinical response by week 4. Three patients (15%) were in remission at week 4 and 2 of these patients (10%) achieved mucosal healing. Three patients (15%) required escalation of care. No serious adverse events were observed. Microbiome analysis revealed that restricted diversity of recipients pre-FMT was significantly increased by high-diversity 2-donor FMP. The microbiome of recipients post-transplant was more similar to the donor FMP than the pretransplant recipient sample in both responders and nonresponders. Notably, donor composition correlated with clinical response. Mucosal CD4 T-cell analysis revealed a reduction in both Th1 and regulatory T-cells post-FMT. High-diversity, 2-donor FMP delivery by colonoscopy seems safe and effective in increasing fecal microbial diversity in patients with active ulcerative colitis. Donor composition correlated with clinical response and further characterization of immunological parameters may provide insight into factors influencing clinical outcome.

Effect of dietary starch source and concentration on equine fecal microbiota

USDA-ARS?s Scientific Manuscript database

Starch from corn is less susceptible to equine small intestinal digestion than starch from oats, and starch that reaches the hindgut can be utilized by the microbiota. The objective of the current study was to examine the effects of starch source on equine fecal microbiota. Thirty horses were assig...

Effect of Lactobacillus salivarius Ls-33 on fecal microbiota in obese adolescents.

PubMed

Larsen, Nadja; Vogensen, Finn K; Gøbel, Rikke Juul; Michaelsen, Kim F; Forssten, Sofia D; Lahtinen, Sampo J; Jakobsen, Mogens

2013-12-01

This study is a part of the clinical trials with probiotic bacterium Lactobacillus salivarius Ls-33 conducted in obese adolescents. Previously reported clinical studies showed no effect of Ls-33 consumption on the metabolic syndrome in the subject group. The aim of the study was to investigate the impact of L. salivarius Ls-33 on fecal microbiota in obese adolescents. The study was a double-blinded intervention with 50 subjects randomized to intake of L. salivarius Ls-33 or placebo for 12 weeks. The fecal microbiota was assessed by real-time quantitative PCR before and after intervention. Concentrations of fecal short chain fatty acids were determined using gas chromatography. Ratios of Bacteroides-Prevotella-Porphyromonas group to Firmicutes belonging bacteria, including Clostridium cluster XIV, Blautia coccoides_Eubacteria rectale group and Roseburia intestinalis, were significantly increased (p ≤ 0.05) after administration of Ls-33. The cell numbers of fecal bacteria, including the groups above as well as Clostridium cluster I, Clostridium cluster IV, Faecalibacterium prausnitzii, Enterobacteriaceae, Enterococcus, the Lactobacillus group and Bifidobacterium were not significantly altered by intervention. Similarly, short chain fatty acids remained unaffected. L. salivarius Ls-33 might modify the fecal microbiota in obese adolescents in a way not related to metabolic syndrome. NCT 01020617. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Saccharomyces cerevisiae colonization associated with fecal microbiota treatment failure

USDA-ARS?s Scientific Manuscript database

Background: Fecal microbiota therapy (FMT) has emerged as the gold standard for treatment of persistent, symptomatic Clostridium difficile infection (CDI) that does not respond to conventional antimicrobial treatment. Probiotics are commonly recommended in addition to antimicrobial treatment for CD...

Modulation of the Fecal Microbiota in Sprague-Dawley Rats Using Genetically Modified and Isogenic Corn Lines.

PubMed

Li, Penggao; Yang, Chun; Yue, Rong; Zhen, Yaping; Zhuo, Qin; Piao, Jianhua; Yang, Xiaoguang; Xiao, Rong

2018-01-17

This study investigated the composition and proportions of fecal microbiota in Sprague-Dawley rats after consuming two genetically modified (GM) corn lines in comparison with the isogenic corn and the AIN93G standard feed for 10 weeks using bar-coded 16S rRNA gene sequencing. As a result, GM corn did not significantly alter the overall health and alpha-diversity of fecal microbiota. Fecal microbiota structures could be separated into noncorn and corn but not non-GM and GM corn subgroups. Both non-GM and GM corn caused the increase in bacterial populations related to carbohydrates utilization, such as Lactobacillus, Barnesiella, and Bifidobacterium, and the reduction in potentially pathogenic populations, such as Tannerella and Moraxellaceae. In conclusion, similar effects on the fecal microbiota were observed after consuming a GM- and non-GM-corn-based diet for long periods. Further studies are warranted to elucidate the functional relevance of the changes in the proportions of bacterial populations in these diets.

Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

PubMed

Maharshak, Nitsan; Ringel, Yehuda; Katibian, David; Lundqvist, Ashley; Sartor, R Balfour; Carroll, Ian M; Ringel-Kulka, Tamar

2018-05-17

Irritable bowel syndrome (IBS) has been associated with changes in the intestinal microbiota. Only a few studies have explored differences in the mucosa-associated microbiota between IBS patients and healthy controls (HC). To characterize and compare the microbiota in mucosal and fecal samples from carefully selected patients with IBS-D and HC. The cohort was composed of 23 diarrhea-predominant IBS (IBS-D) patients and 24 HC. Fresh stool samples were collected from participants prior to the collection of colonic mucosal samples from an unprepped bowel. After DNA extraction, 16S rRNA genes were sequenced by 454 pyrosequencing and analyzed using the QIIME pipeline. The fecal microbiota (luminal niche) of IBS-D patients was found to have reduced enteric richness compared to HC (P < 0.05), whereas no differences were observed between the two groups within the mucosal microbiota. Within the luminal niche, the relative proportions of Faecalibacterium genus were found to be lower in IBS-D than in HC and the Dorea genus was higher in IBS-D. None of the taxa proportions were significantly different in IBS-D patients versus HC using an FDR of ≤ 0.1 when analyzing samples that appeared in > 25% samples of either niche. Fecal and mucosal microbiota of IBS-D patients and HC are very similar and are not sufficient to explain the reported altered physiology and symptomatology of IBS-D. Future studies should investigate intestinal microbiome-dependent functional activity in addition to the fecal and mucosal-associated microbial composition.

Therapeutic manipulation of the microbiota: past, present, and considerations for the future.

PubMed

Young, V B

2016-11-01

The growing appreciation of the potential role of indigenous microbiota in disease has resulted in a concomitant interest in manipulating the microbiome for therapeutic effect. The most successful example of microbiota manipulation for treatment of a disease is in recurrent infection with the bacterial pathogen Clostridium difficile. This review provides historic perspectives on development of microbiota transplantation and reviews evidence for its use in recurrent C. difficile infection. A PubMed search of the terms ([fecal transplant OR fecal transplantation] AND difficile) to 9 June 2016 yielded 415 articles. Recent work has pointed to potential mechanisms by which microbiota restoration in the form of faecal transplantation has been efficacious. This includes studies of microorganisms associated with successful faecal transplantation in human and animal studies and a focus on bacterial bile acid metabolism as a mechanism that mediates colonization resistance against the pathogen. The potential use of microbiota manipulation for other diseases such as inflammatory bowel diseases and metabolic disorders will be discussed. The case will be made that the lessons learned from treatment of recurrent C. difficile infection may not necessarily translate to use of faecal transplantation or other methods to alter the microbiome for the treatment of other diseases. A key conclusion that can be drawn is that understanding of the precise role of the microbiota in the pathogenesis of a specific disease is necessary prior to determining if microbiota manipulation represents a novel treatment therapy. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction.

PubMed

Wang, Wei-Wei; Zhang, Yu; Huang, Xiao-Bing; You, Nan; Zheng, Lu; Li, Jing

2017-10-14

To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl 4 )-induced acute hepatic dysfunction. A rat model of HE was established with CCl 4 . Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined. FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

Fecal excretion of Bifidobacterium infantis 35624 and changes in fecal microbiota after eight weeks of oral supplementation with encapsulated probiotic

PubMed Central

Charbonneau, Duane; Gibb, Roger D.; Quigley, Eamonn M.M.

2013-01-01

Certain randomized, placebo-controlled trials of oral supplementation with B. infantis 35624 have demonstrated the amelioration of symptoms of irritable bowel syndrome. Potential GI colonization by B. infantis 35624 or effects of supplementation on resident GI microbiota may pertain to these clinical observations. In this study, fecal excretion of B. infantis 35624 before, during and after 8 weeks of daily treatment was compared in subjects with IBS who received either the encapsulated oral supplement (n = 39) or placebo (n = 37) and in healthy subjects who received the supplement (n = 41). Secondarily, changes in assessed fecal microbiota and IBS symptoms were determined. Supplementation significantly increased fecal B. infantis 35624 excretion vs. placebo in IBS subjects; excretion in healthy subjects receiving supplement was quantitatively similar. Fecal levels of the probiotic declined and approached baseline once dosing ceased, documenting that colonization is transient. Although supplementation increased numbers of B infantis 35624 within the GI tract, limited changes in 10 other fecal taxa were observed either in healthy subjects or those with IBS. No impact on IBS symptoms was observed. Detection of bacterial DNA in fecal samples suggests that the probiotic is able to survive transit through the GI tract, although strain selective culture techniques were not performed to confirm viability of B. infantis 35624 in the feces. Continuous probiotic administration was necessary to maintain steady-state transit. Given the complex spectrum of GI microbiota, however, monitoring perturbations in selected taxa may not be not a useful indicator of probiotic function. PMID:23549409

Comparison of Fecal Collection Methods for Microbiota Studies in Bangladesh

PubMed Central

Chen, Jun; Kibriya, Muhammad G.; Chen, Yu; Islam, Tariqul; Eunes, Mahbubul; Ahmed, Alauddin; Naher, Jabun; Rahman, Anisur; Amir, Amnon; Shi, Jianxin; Abnet, Christian C.; Nelson, Heidi; Knight, Rob; Chia, Nicholas; Ahsan, Habibul; Sinha, Rashmi

2017-01-01

ABSTRACT To our knowledge, fecal microbiota collection methods have not been evaluated in low- and middle-income countries. Therefore, we evaluated five different fecal sample collection methods for technical reproducibility, stability, and accuracy within the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Fifty participants from the HEALS provided fecal samples in the clinic which were aliquoted into no solution, 95% ethanol, RNAlater, postdevelopment fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT) tubes. Half of the aliquots were frozen immediately at −80°C (day 0) and the remaining samples were left at ambient temperature for 96 h and then frozen (day 4). Intraclass correlation coefficients (ICC) were calculated for the relative abundances of the top three phyla, for two alpha diversity measures, and for four beta diversity measures. The duplicate samples had relatively high ICCs for technical reproducibility at day 0 and day 4 (range, 0.79 to 0.99). The FOBT card and samples preserved in RNAlater and 95% ethanol had the highest ICCs for stability over 4 days. The FIT tube had lower stability measures overall. In comparison to the “gold standard” method using immediately frozen fecal samples with no solution, the ICCs for many of the microbial metrics were low, but the rank order appeared to be preserved as seen by the Spearman correlation. The FOBT cards, 95% ethanol, and RNAlater were effective fecal preservatives. These fecal collection methods are optimal for future cohort studies, particularly in low- and middle-income countries. IMPORTANCE The collection of fecal samples in prospective cohort studies is essential to provide the opportunity to study the effect of the human microbiota on numerous health conditions. However, these collection methods have not been adequately tested in low- and middle-income countries. We present estimates of technical reproducibility, stability at ambient temperature for 4

Gut Microbiota and Energy Expenditure in Health and Obesity.

PubMed

Bakker, Guido J; Zhao, Jing; Herrema, Hilde; Nieuwdorp, Max

2015-01-01

The contribution of intestinal bacterial strains (gut microbiota) to the development of obesity and obesity-related disorders is increasingly recognized as a potential diagnostic and pharmacologic target. Alterations in the intestinal bacterial composition have been associated with presence of chronic low-grade inflammation, a known feature of insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. Fecal transplantation studies in germ-free mice have provided crucial insight into the causality of gut microbiota in development of obesity and obesity-related disorders. Moreover, fecal transplantation studies in conjunction with fecal sampling in prospectively followed cohorts will help identify causally involved intestinal bacterial strains in human obesity. Results from these studies will lead to characterization of novel diagnostic markers as well as therapeutic strategies that aim to treat obesity and obesity-related disorders.

Efficacy and Mechanisms of Action of Fecal Microbiota Transplantation in Ulcerative Colitis: Pitfalls and Promises From a First Meta-Analysis.

PubMed

Scaldaferri, F; Pecere, S; Petito, V; Zambrano, D; Fiore, L; Lopetuso, L R; Schiavoni, E; Bruno, G; Gerardi, V; Laterza, L; Pizzoferrato, M; Ianiro, G; Stojanovic, J; Poscia, A; Papa, A; Paroni Sterbini, F; Sanguinetti, M; Masucci, L; Cammarota, G; Gasbarrini, A

2016-03-01

Inflammatory bowel disease (IBD) is the results of a chronic inflammatory process deriving from disequilibrium between self-microbiota composition and immune response. New evidence, coming from Clostridium difficile infection, clearly showed that active and powerful modulation of microbiota composition by fecal microbiota composition (FMT) is safe, easy to perform, and efficacious, opening new frontiers in gastrointestinal and extra-intestinal diseases. FMT has been proposed also for IBD as well as other non-gastrointestinal conditions related to intestinal microbiota dysfunctions, with good preliminary data. In this setting, ulcerative colitis (UC) represents one of the most robust potential indications for FMT after C difficile colitis. In the present review, we focus on FMT and its application on ulcerative colitis, clarifying mechanisms of actions and efficacy data, trough completion of a meta-analysis on available randomized, controlled trial data in UC. Because microbiota is so crucially involved in this topic, a short review of microbial alterations in UC will also be performed. Copyright © 2016 Elsevier Inc. All rights reserved.

Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice.

PubMed

Sun, Xiaolun; Winglee, Kathryn; Gharaibeh, Raad Z; Gauthier, Josee; He, Zhen; Tripathi, Prabhanshu; Avram, Dorina; Bruner, Steven; Fodor, Anthony; Jobin, Christian

2018-05-01

Campylobacter jejuni, a prevalent foodborne bacterial pathogen, exploits the host innate response to induce colitis. Little is known about the roles of microbiota in C jejuni-induced intestinal inflammation. We investigated interactions between microbiota and intestinal cells during C jejuni infection of mice. Germ-free C57BL/6 Il10 -/- mice were colonized with conventional microbiota and infected with a single dose of C jejuni (10 9 colony-forming units/mouse) via gavage. Conventional microbiota were cultured under aerobic, microaerobic, or anaerobic conditions and orally transplanted into germ-free Il10 -/- mice. Colon tissues were collected from mice and analyzed by histology, real-time polymerase chain reaction, and immunoblotting. Fecal microbiota and bile acids were analyzed with 16S sequencing and high-performance liquid chromatography with mass spectrometry, respectively. Introduction of conventional microbiota reduced C jejuni-induced colitis in previously germ-free Il10 -/- mice, independent of fecal load of C jejuni, accompanied by reduced activation of mammalian target of rapamycin. Microbiota transplantation and 16S ribosomal DNA sequencing experiments showed that Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in fecal samples from mice colonized with microbiota cultured in anaerobic conditions (which reduce colitis) compared with mice fed microbiota cultured under aerobic conditions (susceptible to colitis). Oral administration to mice of microbiota-derived secondary bile acid sodium deoxycholate, but not ursodeoxycholic acid or lithocholic acid, reduced C jejuni-induced colitis. Depletion of secondary bile acid-producing bacteria with antibiotics that kill anaerobic bacteria (clindamycin) promoted C jejuni-induced colitis in specific pathogen-free Il10 -/- mice compared with the nonspecific antibiotic nalidixic acid; colitis induction by antibiotics was associated with reduced level of luminal deoxycholate. We identified a

Fecal Microbiota Transplantation in Combination with Soluble Dietary Fiber for Treatment of Slow Transit Constipation: A Pilot Study.

PubMed

Ge, Xiaolong; Tian, Hongliang; Ding, Chao; Gu, Lili; Wei, Yao; Gong, Jianfeng; Zhu, Weiming; Li, Ning; Li, Jieshou

2016-04-01

Intestinal microbiota and soluble dietary fiber play an important role in intestinal microecology, which is closely related to gut motility. Regulating intestinal microecology comprised of fecal microbiota transplantation (FMT) or fiber supplementation is becoming a novel therapy for functional gastrointestinal disease. We launched this study to evaluate the efficacy and safety of FMT combined with fiber for slow transit constipation (STC). We performed a study of 21 patients with STC. Participants received FMT (via nasojejunal tubes) on 3 consecutive days. After FMT, they were recommended to receive soluble dietary fiber for 4 weeks (8 g, twice daily). Rate of clinical improvement and remission, constipation-related symptoms (PAC-SYM scores), bowel movements per week, colonic transit time (CTT) and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. At the study end, clinical improvement and remission of constipated patients reached 66.7 and 42.9%, respectively. The patients showed an increased stool frequency from 1.7 ± 0.5 per week to 4.8 ± 2.1 per week (p <0.05) and an improved stool consistency after FMT combined with fiber. When compared to pre-treatment, PAC-SYM scores improved significantly from 2.0 ± 0.4 to 1.5 ± 0.6 after treatment (p <0.05). Meanwhile, patients showed an acceleration of colonic transit time from 81.9 ± 9.5 to 53.5 ± 11.2 h at week 12. During follow-up, patients felt satisfied with improved GIQLI. No serious adverse events were observed. This is a pilot study confirming that FMT combined with fiber may improve symptoms experienced by constipated patients by regulating intestinal microecology, without any serious adverse events. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Gut microbiota from twins discordant for obesity modulate metabolism in mice.

PubMed

Ridaura, Vanessa K; Faith, Jeremiah J; Rey, Federico E; Cheng, Jiye; Duncan, Alexis E; Kau, Andrew L; Griffin, Nicholas W; Lombard, Vincent; Henrissat, Bernard; Bain, James R; Muehlbauer, Michael J; Ilkayeva, Olga; Semenkovich, Clay F; Funai, Katsuhiko; Hayashi, David K; Lyle, Barbara J; Martini, Margaret C; Ursell, Luke K; Clemente, Jose C; Van Treuren, William; Walters, William A; Knight, Rob; Newgard, Christopher B; Heath, Andrew C; Gordon, Jeffrey I

2013-09-06

The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.

The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study.

PubMed

Kurokawa, Shunya; Kishimoto, Taishiro; Mizuno, Shinta; Masaoka, Tatsuhiro; Naganuma, Makoto; Liang, Kuo-Ching; Kitazawa, Momoko; Nakashima, Moeko; Shindo, Chie; Suda, Wataru; Hattori, Masahira; Kanai, Takanori; Mimura, Masaru

2018-08-01

The intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms. We followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured. At baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT. The small sample size with no control group. Our results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood. Copyright © 2018 Elsevier B.V. All rights reserved.

Fecal Microbiota Transfer for Multidrug-Resistant Gram-Negatives: A Clinical Success Combined With Microbiological Failure.

PubMed

Stalenhoef, Janneke E; Terveer, Elisabeth M; Knetsch, Cornelis W; Van't Hof, Peter J; Vlasveld, Imro N; Keller, Josbert J; Visser, Leo G; Kuijper, Eduard J

2017-01-01

Combined fecal microbiota transfer and antibiotic treatment prevented recurrences of urinary tract infections with multidrug-resistant (MDR) Pseudomonas aeruginosa , but it failed to eradicate intestinal colonization with MDR Escherichia coli . Based on microbiota analysis, failure was not associated with distinct diminished microbiota diversity.

Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity.

PubMed

Carlucci, Christian; Petrof, Elaine O; Allen-Vercoe, Emma

2016-11-01

The human gut microbiome is a complex ecosystem of fundamental importance to human health. Our increased understanding of gut microbial composition and functional interactions in health and disease states has spurred research efforts examining the gut microbiome as a valuable target for therapeutic intervention. This review provides updated insight into the state of the gut microbiome in recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and obesity while addressing the rationale for the modulation of the gut microbiome using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based therapeutics in pre-clinical or clinical development are discussed. We end by putting this within the context of the current regulatory framework surrounding FMT and related therapies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Comparative analysis of fecal microbiota and intestinal microbial metabolic activity in captive polar bears.

PubMed

Schwab, Clarissa; Gänzle, Michael

2011-03-01

The composition of the intestinal microbiota depends on gut physiology and diet. Ursidae possess a simple gastrointestinal system composed of a stomach, small intestine, and indistinct hindgut. This study determined the composition and stability of fecal microbiota of 3 captive polar bears by group-specific quantitative PCR and PCR-DGGE (denaturing gradient gel electrophoresis) using the 16S rRNA gene as target. Intestinal metabolic activity was determined by analysis of short-chain fatty acids in feces. For comparison, other Carnivora and mammals were included in this study. Total bacterial abundance was approximately log 8.5 DNA gene copies·(g feces)-1 in all 3 polar bears. Fecal polar bear microbiota was dominated by the facultative anaerobes Enterobacteriaceae and enterococci, and the Clostridium cluster I. The detection of the Clostridium perfringens α-toxin gene verified the presence of C. perfringens. Composition of the fecal bacterial population was stable on a genus level; according to results obtained by PCR-DGGE, dominant bacterial species fluctuated. The total short-chain fatty acid content of Carnivora and other mammals analysed was comparable; lactate was detected in feces of all carnivora but present only in trace amounts in other mammals. In comparison, the fecal microbiota and metabolic activity of captive polar bears mostly resembled the closely related grizzly and black bears.

Gut Microbiota and Metabolic Disorders

PubMed Central

Hur, Kyu Yeon

2015-01-01

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

Changes in the composition of the human fecal microbiome following bacteriotherapy for recurrent Clostridium difficile-associated diarrhea

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

Khoruts, A.; Dicksved, J.; Jansson, J.K.

CDAD is the major known cause of antibiotic-induced diarrhea and colitis, and the disease is thought to result from persistent disruption of commensal gut microbiota. Bacteriotherapy by way of fecal transplantation can be used to treat recurrent CDAD and is thought to re-establish the normal colonic microflora. However, limitations of conventional microbiologic techniques have until recently precluded testing of this idea. In this study we used T-RFLP and 16S rRNA gene sequencing approaches to characterize the bacterial composition of the colonic microflora in a patient suffering from recurrent CDAD, before and after treatment by fecal transplantation from a healthy donor.more » While the patient's residual colonic microbiota, prior to therapy, was deficient in members of the bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic impact on the composition of the patient's gut microbiota. By 14 days post transplantation, the fecal bacterial composition of the recipient was highly similar to the donor and was dominated by Bacteroides spp. strains and an uncharacterized butyrate producing bacterium. The change in bacterial composition was accompanied by resolution of the patient's symptoms. The striking similarity of the recipient's and donor's intestinal microbiota following bacteriotherapy suggests that the donor's bacteria quickly occupied their requisite niches, resulting in restoration of both the structure and function of the microbial communities present.« less

Comparison of the fecal microbiota of domestic commercial meat, laboratory, companion, and shelter rabbits (Oryctolagus cuniculi).

PubMed

Kylie, Jennifer; Weese, J Scott; Turner, Patricia V

2018-04-27

Rabbits are cecotrophic, hindgut-fermenters that rely heavily on their gastrointestinal microbiota for optimal digestion of plant-based diets. Dysbiosis, caused by disruption of the gastrointestinal microbiota, is known to predispose rabbits to rabbit enteritis complex (REC), a major cause of morbidity and mortality. The objectives of this study were to describe the fecal microbiota of domestic rabbits from a variety of settings (commercial meat, companion, laboratory, and shelter) and to identify how factors such as age, season, and routine antimicrobial use affect the fecal microbiota composition. A total of 86 pooled commercial meat, 54 companion, 14 pooled laboratory, and 14 shelter rabbit fecal samples were evaluated using 16S rRNA gene sequencing of the V4 region. In all sample types, the predominant bacterial phylum was Firmicutes. Other commonly identified phyla (composing ≥ 1% of the total microbiota composition) were Verrucomicrobia, Proteobacteria, and Bacteroidetes. Significant differences in composition were noted between commercial, companion, laboratory, and shelter rabbit samples for proportions of Verrucomicrobia (P < 0.01), Proteobacteria (P < 0.01), and Lentisphaerae (P = 0.01) within the total microbiota. Within the commercial meat rabbit samples, significant differences between the microbiota composition of growers (n = 42) and does (n = 44) were limited to one unclassified Firmicutes (P = 0.03) and no differences were identified at the phylum level. Significant differences were present between fecal samples taken from rabbits during the summer (n = 44) compared to the winter (n = 42), with Firmicutes (P = 0.04), Verrucomicrobia (P = 0.03), Proteobacteria (P = 0.02), Deinococcus-Thermus (P = 0.04), Armatimonadates (P = 0.003), and Actinobacteria (P = 0.03) forming significantly different proportions of the microbiota. The only significant difference in composition between those farms

Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease.

PubMed

Maukonen, Johanna; Kolho, Kaija-Leena; Paasela, Monika; Honkanen, Jarno; Klemetti, Paula; Vaarala, Outi; Saarela, Maria

2015-12-01

Several factors support the view of inflammatory bowel disease [IBD] origin in the host responsiveness to intestinal bacteria, although no single bacterial species has been shown as a causative agent in the pathogenesis. Our aim was to analyse the fecal microbiota of paediatric IBD patients at different stages of the disease. In addition, the characteristics of immune response to the bacterial isolates showing very low abundance in IBD were studied. Fecal samples [1-3 samples/child] were collected from 10 paediatric patients with crohn's disease [CD], and 12 with ulcerative colitis [UC] and from 8 healthy children, for polyphasic microbiological analysis (culture, real-time polymerase chain reaction [PCR], and denaturing gradient gel electrophoresis). In addition, in vitro cytokine responses of peripheral blood mononuclear cells to the bacterial isolates, which showed very low abundance in IBD, were studied. Although predominant bacterial diversity was higher in IBD, the numbers of Lachnospiraceae and Coriobacteriaceae bacteria were lower in IBD patients as compared with control children [p < 0.05]. In addition, Ruminococcaceae population diversity was lower in IBD [p < 0.05] and correlated negatively with fecal calprotectin levels. Both abundance and diversity of bifidobacterial populations were lower in children with IBD [p < 0.05], and particularly low numbers of certain bifidobacterial isolates were detected. In CD, we found enhanced up-regulation of interleukin-6 transcripts and impaired RAR-related orphan receptor C response to bifidobacteria, whereas decreased interferon-gamma response was observed in both CD and UC. We demonstrate altered fecal microbiota in paediatric IBD, particularly low numbers and diversity of bifidobacterial populations. Interestingly, immunological response to bifidobacteria differed between paediatric CD patients and control children. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford

[Breaking paradigms. Intestinal microbiota transplantation: Preliminar report].

PubMed

Zamudio-Tiburcio, Álvaro; Bermúdez-Ruiz, Héctor; Lezama-Guzmán, Hugo Ricardo; Guevara-Ortigoza, María Del Pilar; Islas-Solares, Elena; Sosa-López, Francisco Antonio

2017-12-01

In the fourth century, during the Chinese Dong Jin dynasty, the doctor Ge Hong described good results after the oral administration of a suspension prepared from human faeces in patients with severe diarrhoea or food poisoning. Faecal microbiota transplantation has been used for five years in order to treat different diseases in addition to the severe diarrhoea caused by Clostridium difficile 1 . This paper aims to confirm that intestinal microbiota transplantation succeeds in reducing the negative impact of diseases such as severe diarrhoea, irritable bowel syndrome, anxiety, allergies, metabolic syndrome and others and that it is not only indicated for severe diarrhoea caused by C. difficile. This preliminary study included six patients who underwent faecal microbiota transplantation, aged 83, 76, 66, 37 and 36 years (four men and two women). An improvement in symptoms of 70% was observed. The methodology and criteria to be followed with donors are described and the results are listed in three tables. The methodology followed for the microbiota transplant is the same as that reported by other researchers for the treatment of C. difficile diarrhoea and other diseases. The discussion addresses the issues raised in other parts of the world in handling different pathologic entities, as well as genetic advances. The conclusions show encouraging results. Copyright © 2017 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Gut microbiota and its implications in small bowel transplantation.

PubMed

Wang, Chenyang; Li, Qiurong; Li, Jieshou

2018-06-01

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Sun, Dali; Li, Weiming; Li, Shumin; Cen, Yunyun; Xu, Qingwen; Li, Yijun; Sun, Yanbo; Qi, Yuxing; Lin, Yueying; Yang, Ting; Xu, Pengyuan; Lu, Qiping

2016-06-01

Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC.A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome.Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6-39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events.FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT.

Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Luo, Zhuanbo; Li, Zhengfeng; Deng, Min; Liu, Hao; Zhu, Biao; Ruan, Bing; Li, Lanjuan

2012-08-01

Bacterial translocation and the development of sepsis after orthotopic liver transplantation (OLT) may be promoted by immunological damage to the intestinal mucosa or by quantitative and qualitative changes in intestinal microbiota. This study monitored structural shifts of gut microbiota in rats with OLT using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR (RT-qPCR). RT-qPCR targets six major microorganisms (Domain Bacteria, Bacteroides, Bifidobacteria, Enterobacteriaceae, Lactobacillus and Clostridium leptum subgroup). Isograft, Allograft and Sham model were studied. Bacterial translocation to host organs and plasma endotoxin were determined. Alteration in gut microbiota was associated with the elevation of plasma endotoxin and a higher rate of bacterial translocation (BT) to liver in rats with acute rejection. Dynamic analysis of DGGE fingerprints showed that the gut microbiota structure of animals in the three groups was similar before the operation. But significant alterations in the composition of fecal microbiota in Allograft group were observed at 1 and 2 weeks after the OLT. The acute rejection was accompanied by the shifts of gut microbiota towards members of Bacteroides and Ruminococcus. Results from RT-qPCR indicated that Bacteroides significantly increased at 2 weeks after the OLT, whereas numbers of Bifidobacterium spp. decreased at 1 week and recovered at 2 weeks after the OLT. In summary, our data showed that rats with acute rejection after OLT exhibited significant structure shifts in the gut microbiota which dominant by overgrowth of Bacteroides and Ruminococcus, and these were associated with elevation of plasma endotoxin and higher rate of BT.

Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up.

PubMed

Ding, Chao; Fan, Wenting; Gu, Lili; Tian, Hongliang; Ge, Xiaolong; Gong, Jianfeng; Nie, Yongzhan; Li, Ning

2018-05-01

Gut microbiota may contribute to regulate colonic motility, which is involved in the etiology of constipation. Fecal microbiota transplantation (FMT) has been demonstrated to restore intestinal homeostasis. The aim of this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation (STC). Fifty-two patients with STC received standardized FMT and were followed up for 6 months. Bowel habit, colonic transit time, constipation-related symptoms (PAC-SYM score), quality of life (PAC-QOL score), treatment satisfaction scores and adverse events were monitored. The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements (CSBMs) per week. The primary efficacy endpoint was achieved in 50.0%, 38.5% and 32.7% of patients over week intervals 3-4, 9-12 and 21-24, respectively ( P  < 0.01 for all comparisons). Significant improvements were also observed in other bowel movement assessments, colonic transit time, constipation-related symptoms and quality of life; but all improvements diminished at weeks 12 and 24. Incompleteness of evacuation served as the only factor associated with efficacy. No serious treatment-related adverse events were observed. This study suggested FMT was effective and safe for STC, while a late loss of efficacy was also observed. A lower degree of sensation of incompleteness predicted a better outcome.

Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

PubMed Central

Vincent, Caroline; Manges, Amee R.

2015-01-01

Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material. PMID:27025623

[Short-term efficacy on fecal microbiota transplantation combined with soluble dietary fiber and probiotics in the treatment of slow transit constipation].

PubMed

Ge, Xiaolong; Ding, Chao; Gong, Jianfeng; Tian, Hongliang; Wei, Yao; Chen, Qiyi; Gu, Lili; Li, Ning

2016-12-25

To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) combined with soluble dietary fiber and probiotics for slow transit constipation(STC). Twenty-three patients with STC from Jinling Hospital, Medical School of Nanjing University were prospectively enrolled between April 2015 and January 2016. STC patients received FMT combined with soluble dietary fiber and probiotics. Fresh stool(100 g) was immediately mixed in a blender with 500 ml of 0.9% sterile saline for several seconds, which was then filtered through a gauze pad and a decreasing number of gauze screen (2.0 to 0.5 mm). The fecal bacteria suspension was stored frozen at -20centi-degree. The preparation time of FMT material was less than 1 hour. Total time of treatment was 9 days. An initial oral antibiotics(vancomycin 500 mg orally twice per day) was given for 3 consecutive days. Then the fecal microbiota(100 ml) was infused slowly(5 min) through nasojejunal tube for 6 consecutive days. After FMT, patients were recommended to receive soluble dietary fiber (pectin, 8 g/d) and probiotics (bifid triple viable capsules, twice per day) for 4 weeks. Rates of clinical improvement and remission, adverse events, constipation-related symptoms (PAC-SYM scores), bowel movements per week and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. This study was registered in the Clinical Trials.gov (NCT02016469). Among 23 patients, 7 were male, 16 were female, the mean age was (49.6±14.7) years, the body mass index was (21.2±2.2) kg/m 2 , the duration of constipation was (8.3±5.9) years, and the defecation frequency was 1.8±0.7 per week. Compared with pre-treatment, PAC-SYM scores decreased significantly from 2.3±0.5 to 1.3±0.4 at week 12 (P<0.01), defecation frequency increased from 1.8±0.7 per week to 4.8±2.0 per week at week 12 (P<0.01), and patients felt satisfied with improved GIQLI score (from 78.5±15.5 to 120.8±21.3, P<0.01). During the follow

Characterization of the fecal and mucosa-associated microbiota in dogs with colorectal epithelial tumors.

PubMed

Herstad, Kristin Marie Valand; Moen, Aina Elisabeth Fossum; Gaby, John Christian; Moe, Lars; Skancke, Ellen

2018-01-01

Colorectal epithelial tumors occur spontaneously in dogs, and the pathogenesis seems to parallel that of humans. The development of human colorectal tumorigenesis has been linked to alterations in the composition of the intestinal microbiota. This study characterized the fecal- and mucosa-associated microbiota in dogs with colorectal epithelial tumors (n = 10). The fecal microbiota was characterized by 16S rDNA analysis and compared with that of control dogs (n = 13). We also determined the mucosa-associated microbiota composition in colonic tumor tissue (n = 8) and in adjacent non-tumor tissue (n = 5) by 16S rDNA- and rRNA profiling. The fecal microbial community structure in dogs with tumors was different from that of control samples and was distinguished by oligotypes affiliated with Enterobacteriaceae, Bacteroides, Helicobacter, Porphyromonas, Peptostreptococcus and Streptococcus, and lower abundance of Ruminococcaceae, Slackia, Clostridium XI and Faecalibacterium. The overall community structure and populations of mucosal bacteria were not different based on either the 16S rDNA or the 16S rRNA profile in tumor tissue vs. adjacent non-tumor tissue. However, the proportion of live, potentially active bacteria appeared to be higher in non-tumor tissue compared with tumor tissue and included Slackia, Roseburia, unclass. Ruminococcaeceae, unclass. Lachnospiraceae and Oscillibacter. Colorectal tumors are rarely diagnosed in dogs, but despite this limitation, we were able to show that dogs with colorectal tumors have distinct fecal microbiota profiles. These initial results support the need for future case-control studies that are adequately powered, as well as age-matched and breed-matched, in order to evaluate the influence of bacteria on colorectal cancer etiopathogenesis and to determine whether the bacteria may have potential as biomarkers in clinical settings.

Influence of Hand Rearing and Bird Age on the Fecal Microbiota of the Critically Endangered Kakapo

PubMed Central

Waite, David W.; Eason, Daryl K.

2014-01-01

The critically endangered New Zealand parrot, the kakapo, is subject to an intensive management regime aiming to maintain bird health and boost population size. Newly hatched kakapo chicks are subjected to human intervention and are frequently placed in captivity throughout their formative months. Hand rearing greatly reduces mortality among juveniles, but the potential long-term impact on the kakapo gut microbiota is uncertain. To track development of the kakapo gut microbiota, fecal samples from healthy, prefledged juvenile kakapos, as well as from unrelated adults, were analyzed by using 16S rRNA gene amplicon pyrosequencing. Following the original sampling, juvenile kakapos underwent a period of captivity, so further sampling during and after captivity aimed to elucidate the impact of captivity on the juvenile gut microbiota. Variation in the fecal microbiota over a year was also investigated, with resampling of the original juvenile population. Amplicon pyrosequencing revealed a juvenile fecal microbiota enriched with particular lactic acid bacteria compared to the microbiota of adults, although the overall community structure did not differ significantly among kakapos of different ages. The abundance of key operational taxonomic units (OTUs) was correlated with antibiotic treatment and captivity, although the importance of these factors could not be proven unequivocally within the bounds of this study. Finally, the microbial community structure of juvenile and adult kakapos changed over time, reinforcing the need for continual monitoring of the microbiota as part of regular health screening. PMID:24837385

Fecal Microbiota Composition of Breast-fed Infants is Correlated with Human Milk Oligosaccharides Consumed

PubMed Central

Wang, Mei; Li, Min; Wu, Shuai; Lebrilla, Carlito B.; Chapkin, Robert S.; Ivanov, Ivan; Donovan, Sharon M.

2015-01-01

Objectives This study tested the hypothesis that the fecal bacterial genera of breast-fed (BF) and formula-fed (FF) infants differ and that human milk oligosaccharides (HMO) modulate the microbiota of BF infants. Methods Fecal samples were obtained from BF (n = 16) or FF (n = 6) infants at 3-month postpartum. Human milk were collected on the same day when feces were collected. The microbiota was assessed by pyrosequencing of bacterial 16S rRNA genes. HMO were measured by HPLC-Chip time-of-flight mass spectrometry. Results The overall microbiota of BF differed from that of FF (P = 0.005). Compared to FF, BF had higher relative abundances of Bacteroides, lower proportions of Clostridium XVIII, Lachnospiracea incertae sedis, Streptococcus, Enterococcus and Veillonella (P < 0.05). Bifidobacterium predominated in both BF and FF infants, with no difference in abundance between the two groups. The most abundant HMO were lacto-N-tetraose + lacto-N-neotetraose (LNT + LNnT, 22.6%), followed by 2′-fucosyllactose (2′FL, 14.5%) and lacto-N-fucopentaose I (LNFP I, 9.5%). Partial least squares regression of HMO and microbiota showed several infant fecal bacterial genera could be predicted by their mothers’ HMO profiles and the important HMO for the prediction of bacterial genera were identified by variable importance in the projection scores. Conclusions These results strengthen the established relationship between HMO and the infant microbiota, identify statistical means whereby infant bacterial genera can be predicted by milk HMO. Future studies are needed to validate these findings and determine if supplementation of formula with defined HMO could selectively modify the gut microbiota. PMID:25651488

Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by Screening: A Population-based Study

PubMed Central

Goedert, James J.; Gong, Yangming; Hua, Xing; Zhong, Huanzi; He, Yimin; Peng, Peng; Yu, Guoqin; Wang, Wenjing; Ravel, Jacques; Shi, Jianxin; Zheng, Ying

2015-01-01

Background Screening for colorectal cancer (CRC) and precancerous colorectal adenoma (CRA) can detect curable disease. However, participation in colonoscopy and sensitivity of fecal heme for CRA are low. Methods Microbiota metrics were determined by Illumina sequencing of 16S rRNA genes amplified from DNA extracted from feces self-collected in RNAlater. Among fecal immunochemical test-positive (FIT +) participants, colonoscopically-defined normal versus CRA patients were compared by regression, permutation, and random forest plus leave-one-out methods. Findings Of 95 FIT + participants, 61 had successful fecal microbiota profiling and colonoscopy, identifying 24 completely normal patients, 20 CRA patients, 2 CRC patients, and 15 with other conditions. Phylum-level fecal community composition differed significantly between CRA and normal patients (permutation P = 0.02). Rank phylum-level abundance distinguished CRA from normal patients (area under the curve = 0.767, permutation P = 0.006). CRA prevalence was 59% in phylum-level cluster B versus 20% in cluster A (exact P = 0.01). Most of the difference reflected 3-fold higher median relative abundance of Proteobacteria taxa (Wilcoxon signed-rank P = 0.03, positive predictive value = 67%). Antibiotic exposure and other potential confounders did not affect the associations. Interpretation If confirmed in larger, more diverse populations, fecal microbiota analysis might be employed to improve screening for CRA and ultimately to reduce mortality from CRC. PMID:26288821

Clostridium difficile infection in solid organ transplant recipients.

PubMed

Nanayakkara, Deepa; Nanda, Neha

2017-08-01

Clostridium difficile infection (CDI) is a major healthcare-associated infection that causes significant morbidity and an economic impact in the United States. In this review, we provide an overview of Clostridium difficile infection in solid organ transplant recipients with an emphasis on recent literature. C. difficile in solid organ transplant population has unique risk factors. Fecal microbiota transplantation has shown favorable results in treatment of recurrent C. difficile in this population. Preliminary data from animal studies suggests excellent efficacy with immunization against C. difficile toxins. Over the last decade, number of individuals receiving solid organ transplants has increased exponentially making peri-transplant complications a common occurrence.C. difficile is a frequent cause of morbidity in solid organ transplant recipients. Early and accurate diagnosis of C. difficile requires a stepwise approach. Differentiating between asymptomatic carriage and infection is a diagnostic challenge. Microbial diversity is inversely proportional to risk of C. difficile infection. Antimicrobial stewardship programs help to retain microbial diversity in individuals susceptible to CDI. Recurrent or relapsing C. difficile infection require fecal microbiota transplantation for definitive cure.

Hypogonadism alters cecal and fecal microbiota in male mice.

PubMed

Harada, Naoki; Hanaoka, Ryo; Hanada, Kazuki; Izawa, Takeshi; Inui, Hiroshi; Yamaji, Ryoichi

2016-11-01

Low testosterone levels increase the risk for cardiovascular disease in men and lead to shorter life spans. Our recent study showed that androgen deprivation via castration altered fecal microbiota and exacerbated risk factors for cardiovascular disease, including obesity, impaired fasting glucose, excess hepatic triglyceride accumulation, and thigh muscle weight loss only in high-fat diet (HFD)-fed male mice. However, when mice were administered antibiotics that disrupted the gut microbiota, castration did not increase cardiovascular risks or decrease the ratio of dried feces to food intake. Here, we show that changes in cecal microbiota (e.g., an increased Firmicutes/Bacteroidetes ratio and number of Lactobacillus species) were consistent with changes in feces and that there was a decreased cecal content secondary to castration in HFD mice. Castration increased rectal body temperature and plasma adiponectin, irrespective of diet. Changes in the gut microbiome may provide novel insight into hypogonadism-induced cardiovascular diseases.

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

2014-11-01

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

Fecal Microbiota Differences According to the Risk of Advanced Colorectal Neoplasms.

PubMed

Yang, Hyo-Joon; Kwon, Min-Jung; Chang, Yoosoo; Song, Seul-Ki; Ahn, Kwang-Sung; Kim, Han-Na; Yun, Yeojun; Kim, Hyung-Lae; Park, Dong Il

2018-02-09

This study aimed to compare differences in the fecal microbiota according to the risk of advanced colorectal neoplasia (ACN) based on a risk-score model in a large Korean cohort. Stool samples were collected from 1122 health screening recipients: 404 enrolled in the average risk (AR) group, 514 in the moderate risk (MR) group, and 204 in the high risk (HR) group, in accordance with their risk of ACN. The fecal microbiota was characterized using pyrosequencing of the V3-V4 region of the 16S rRNA genes. The overall microbial diversity was significantly reduced with an increased risk of ACN [false discovery rate (FDR), P<0.001], and the composition was significantly different between the risk groups (Bonferroni corrected, P<0.05). On taxonomic comparison, 6 of 11 phyla and 39 of 88 genera were significantly different among the risk groups (all FDR P<0.05). These included under-representation of Bacteroides, Ruminococcus, and Bifidobacterium, and over-representation of Prevotella and Fusobacterium with an increased risk of ACN. In particular, we observed that the unknown genus of Ruminococcaceae were relatively abundant (16.2%) in the AR group and significantly depleted with an increased risk of ACN (13.5% in the HR group; FDR P<0.001). These findings support the hypothesis that the fecal microbiota is different according to the risk of ACN. An unknown genus of Ruminococcaceae, as novel potential butyrate producers, might have a possible role in colorectal tumorigenesis in the Korean population.

Dihydrodaidzein-producing Clostridium-like intestinal bacterium, strain TM-40, affects in vitro metabolism of daidzein by fecal microbiota of human male equol producer and non-producers.

PubMed

Tamura, Motoi; Hori, Sachiko; Nakagawa, Hiroyuki

2011-01-01

Much attention has been focused on the biological effects of equol, a metabolite of daidzein produced by intestinal microbiota. However, little is known about the role of isoflavone metabolizing bacteria in the intestinal microbiota. Recently, we isolated a dihydrodaidzein (DHD)-producing Clostridium-like bacterium, strain TM-40, from human feces. We investigated the effects of strain TM-40 on in vitro daidzein metabolism by human fecal microbiota from a male equol producer and two male equol non-producers. In the fecal suspension from the male equol non-producer and DHD producer, DHD was detected in the in vitro fecal incubation of daidzein after addition of TM-40. The DHD concentration increased as the concentration of strain TM-40 increased. In the fecal suspension from the equol producer, the fecal equol production was increased by the addition of strain TM-40. The occupation ratios of Bifidobacterium and Lactobacillales were higher in the equol non-producers than in the equol producer. Adding isoflavone-metabolizing bacteria to the fecal microbiota should facilitate the estimation of the metabolism of isoflavonoids by fecal microbiota. Studies on the interactions among equol-producing microbiota and DHD-producing bacteria might lead to clarification of some of the mechanisms regulating the production of equol by fecal microbiota.

Dihydrodaidzein-producing Clostridium-like intestinal bacterium, strain TM-40, affects in vitro metabolism of daidzein by fecal microbiota of human male equol producer and non-producers

PubMed Central

TAMURA, Motoi; HORI, Sachiko; NAKAGAWA, Hiroyuki

2011-01-01

Much attention has been focused on the biological effects of equol, a metabolite of daidzein produced by intestinal microbiota. However, little is known about the role of isoflavone metabolizing bacteria in the intestinal microbiota. Recently, we isolated a dihydrodaidzein (DHD)-producing Clostridium-like bacterium, strain TM-40, from human feces. We investigated the effects of strain TM-40 on in vitro daidzein metabolism by human fecal microbiota from a male equol producer and two male equol non-producers. In the fecal suspension from the male equol non-producer and DHD producer, DHD was detected in the in vitro fecal incubation of daidzein after addition of TM-40. The DHD concentration increased as the concentration of strain TM-40 increased. In the fecal suspension from the equol producer, the fecal equol production was increased by the addition of strain TM-40. The occupation ratios of Bifidobacterium and Lactobacillales were higher in the equol non-producers than in the equol producer. Adding isoflavone-metabolizing bacteria to the fecal microbiota should facilitate the estimation of the metabolism of isoflavonoids by fecal microbiota. Studies on the interactions among equol-producing microbiota and DHD-producing bacteria might lead to clarification of some of the mechanisms regulating the production of equol by fecal microbiota. PMID:25045313

Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice.

PubMed

Zhan, Gaofeng; Yang, Ning; Li, Shan; Huang, Niannian; Fang, Xi; Zhang, Jie; Zhu, Bin; Yang, Ling; Yang, Chun; Luo, Ailin

2018-06-10

Alzheimer's disease is characterized by cognitive dysfunction and aging is an important predisposing factor; however, the pathological and therapeutic mechanisms are not fully understood. Recently, the role of gut microbiota in Alzheimer's disease has received increasing attention. The cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice was significantly decreased and the Chao 1 and Shannon indices, principal coordinates analysis, and principal component analysis results were notably abnormal compared with that of those in senescence-accelerated mouse resistant 1 (SAMR1) mice. Moreover, 27 gut bacteria at six phylogenetic levels differed between SAMP8 and SAMR1 mice. In a separate study, we transplanted fecal bacteria from SAMP8 or SAMR1 mice into pseudo germ-free mice. Interestingly, the pseudo germ-free mice had significantly lower cognitive function prior to transplant. Pseudo germ-free mice that received fecal bacteria transplants from SAMR1 mice but not from SAMP8 mice showed improvements in behavior and in α-diversity and β-diversity indices. In total, 14 bacteria at six phylogenetic levels were significantly altered by the gut microbiota transplant. These results suggest that cognitive dysfunction in SAMP8 mice is associated with abnormal composition of the gut microbiota. Thus, improving abnormal gut microbiota may provide an alternative treatment for cognitive dysfunction and Alzheimer's disease.

Comparative analyses of fecal microbiota in Tibetan and Chinese Han living at low or high altitude by barcoded 454 pyrosequencing

PubMed Central

Li, Long; Zhao, Xin

2015-01-01

Knowledge about the impact of altitude and ethnicity on human gut microbiota is currently limited. In this study, fecal microbiota from 12 Tibetans (T group), 11 Chinese Han living in Tibet (HH group) and 12 Chinese Han living in Shaanxi province (LH group) were profiled by 454 pyrosequencing. Analysis of UniFrac principal coordinates showed significant structural changes in fecal microbiota among the three groups. There were significant differences in the composition of fecal microbiota among the three groups at phylum and genus levels. At the phylum level, the fecal samples of HH and T groups had higher relative abundances of Firmicutes, whereas the LH group had a higher relative abundance of Bacteroidetes. These changes at the phylum level reflected different dominant genus compositions. Compared with the LH group, changes of Firmicutes and Bacteroidetes were mainly due to a significant decrease of Prevotella in the HH group and were primarily attributable to significant decreases of Bacteroides and Prevotella as well as a significant increase of Catenibacterium in the T group. In conclusion, our results suggest that high altitude may contribute to shaping human gut microbiota. Genetic and dietary factors may also explain the different microbiota compositions between Tibetan and Chinese Han. PMID:26443005

Fecal Microbiota Transplantation, Commensal Escherichia coli and Lactobacillus johnsonii Strains Differentially Restore Intestinal and Systemic Adaptive Immune Cell Populations Following Broad-spectrum Antibiotic Treatment.

PubMed

Ekmekciu, Ira; von Klitzing, Eliane; Neumann, Christian; Bacher, Petra; Scheffold, Alexander; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

The essential role of the intestinal microbiota in the well-functioning of host immunity necessitates the investigation of species-specific impacts on this interplay. Aim of this study was to examine the ability of defined Gram-positive and Gram-negative intestinal commensal bacterial species, namely Escherichia coli and Lactobacillus johnsonii , respectively, to restore immune functions in mice that were immunosuppressed by antibiotics-induced microbiota depletion. Conventional mice were subjected to broad-spectrum antibiotic treatment for 8 weeks and perorally reassociated with E. coli , L. johnsonii or with a complex murine microbiota by fecal microbiota transplantation (FMT). Analyses at days (d) 7 and 28 revealed that immune cell populations in the small and large intestines, mesenteric lymph nodes and spleens of mice were decreased after antibiotic treatment but were completely or at least partially restored upon FMT or by recolonization with the respective bacterial species. Remarkably, L. johnsonii recolonization resulted in the highest CD4+ and CD8+ cell numbers in the small intestine and spleen, whereas neither of the commensal species could stably restore those cell populations in the colon until d28. Meanwhile less efficient than FMT, both species increased the frequencies of regulatory T cells and activated dendritic cells and completely restored intestinal memory/effector T cell populations at d28. Furthermore, recolonization with either single species maintained pro- and anti-inflammatory immune functions in parallel. However, FMT could most effectively recover the decreased frequencies of cytokine producing CD4+ lymphocytes in mucosal and systemic compartments. E. coli recolonization increased the production of cytokines such as TNF, IFN-γ, IL-17, and IL-22, particularly in the small intestine. Conversely, only L. johnsonii recolonization maintained colonic IL-10 production. In summary, FMT appears to be most efficient in the restoration of

Fecal Microbiota Transplantation, Commensal Escherichia coli and Lactobacillus johnsonii Strains Differentially Restore Intestinal and Systemic Adaptive Immune Cell Populations Following Broad-spectrum Antibiotic Treatment

PubMed Central

Ekmekciu, Ira; von Klitzing, Eliane; Neumann, Christian; Bacher, Petra; Scheffold, Alexander; Bereswill, Stefan; Heimesaat, Markus M.

2017-01-01

The essential role of the intestinal microbiota in the well-functioning of host immunity necessitates the investigation of species-specific impacts on this interplay. Aim of this study was to examine the ability of defined Gram-positive and Gram-negative intestinal commensal bacterial species, namely Escherichia coli and Lactobacillus johnsonii, respectively, to restore immune functions in mice that were immunosuppressed by antibiotics-induced microbiota depletion. Conventional mice were subjected to broad-spectrum antibiotic treatment for 8 weeks and perorally reassociated with E. coli, L. johnsonii or with a complex murine microbiota by fecal microbiota transplantation (FMT). Analyses at days (d) 7 and 28 revealed that immune cell populations in the small and large intestines, mesenteric lymph nodes and spleens of mice were decreased after antibiotic treatment but were completely or at least partially restored upon FMT or by recolonization with the respective bacterial species. Remarkably, L. johnsonii recolonization resulted in the highest CD4+ and CD8+ cell numbers in the small intestine and spleen, whereas neither of the commensal species could stably restore those cell populations in the colon until d28. Meanwhile less efficient than FMT, both species increased the frequencies of regulatory T cells and activated dendritic cells and completely restored intestinal memory/effector T cell populations at d28. Furthermore, recolonization with either single species maintained pro- and anti-inflammatory immune functions in parallel. However, FMT could most effectively recover the decreased frequencies of cytokine producing CD4+ lymphocytes in mucosal and systemic compartments. E. coli recolonization increased the production of cytokines such as TNF, IFN-γ, IL-17, and IL-22, particularly in the small intestine. Conversely, only L. johnsonii recolonization maintained colonic IL-10 production. In summary, FMT appears to be most efficient in the restoration of

Intestinal microbiota in liver disease.

PubMed

Haque, Tanvir R; Barritt, A Sidney

2016-02-01

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. Copyright © 2016. Published by Elsevier Ltd.

Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota Transplant in Children With Inflammatory Bowel Disease.

PubMed

Goyal, Alka; Yeh, Andrew; Bush, Brian R; Firek, Brian A; Siebold, Leah M; Rogers, Matthew Brian; Kufen, Adam D; Morowitz, Michael J

2018-01-18

The role of fecal microbiota transplant (FMT) in the treatment of pediatric inflammatory bowel disease (IBD) is unknown. The aims of this study were to assess safety, clinical response, and gut microbiome alterations in children with Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC). In this open-label, single-center prospective trial, patients with IBD refractory to medical therapy underwent a single FMT by upper and lower endoscopy. Adverse events, clinical response, gut microbiome, and biomarkers were assessed at baseline, 1 week, 1 month, and 6 months following FMT. Twenty-one subjects were analyzed, with a median age of 12 years, of whom 57% and 28% demonstrated clinical response at 1 and 6 months post-FMT, respectively. Two CD patients were in remission at 6 months. Adverse events attributable to FMT were mild to moderate and self-limited. Patients prior to FMT showed decreased species diversity and significant microbiome compositional differences characterized by increased Enterobacteriaceae, Enterococcus, Haemophilus, and Fusobacterium compared with donors and demonstrated increased species diversity at 30 days post-FMT. At 6 months, these changes shifted toward baseline. Clinical responders had a higher relative abundance of Fusobacterium and a lower diversity at baseline, as well as a greater shift toward donor-like microbiome after FMT compared with nonresponders. A single FMT is relatively safe and can result in a short-term response in young patients with active IBD. Responders possessed increased Fusobacterium prior to FMT and demonstrated more significant microbiome changes compared with nonresponders after FMT. Microbiome characteristics may help in predicting response. © 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis

PubMed Central

Uygun, Ahmet; Ozturk, Kadir; Demirci, Hakan; Oger, Cem; Avci, Ismail Yasar; Turker, Turker; Gulsen, Mustafa

2017-01-01

Abstract Background: Fecal microbial transplantation (FMT) provides to replace beneficial bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of the present study was to prospectively investigate the efficacy of FMT by assessing the clinical and endoscopic response in patients with ulcerative colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy. Methods: In this prospective and uncontrolled study, 30 patients with UC were included. All medications except mesalazine were stopped 4 weeks before FMT. Colonoscopy was performed both before and after FMT. To assess the efficacy of FMT, Mayo scores were calculated at week 0 and week 12. A total of 500 mL extracted fresh fecal suspension was administered into the 30 to 40 cm proximal of terminal ileum of recipients. Results: After FMT, 21 of the (70%) 30 patients showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and endoscopic remission at the week 12. Nine patients (30%) were accepted as a nonresponder at the end of the week 12. There was no significant difference among donors concerning both the rate of clinical remission and clinical response. No adverse events were observed in the majority of patients during FMT and 12 weeks follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea, vomiting, abdominal pain, diarrhea, and fewer after FMT. Conclusion: FMT could be considered as a promising rescue treatment modality before surgery in patients with refractory UC. Besides, FMT also appears to be definitely safer and more tolerable than the immunosuppressive therapy in patients with UC (NCT02575040). PMID:28422836

Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon

PubMed Central

Fehlbaum, Sophie; Chassard, Christophe; Haug, Martina C.; Fourmestraux, Candice; Derrien, Muriel; Lacroix, Christophe

2015-01-01

In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor’s fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source. PMID:26559530

Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon.

PubMed

Fehlbaum, Sophie; Chassard, Christophe; Haug, Martina C; Fourmestraux, Candice; Derrien, Muriel; Lacroix, Christophe

2015-01-01

In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor's fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source.

Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome.

PubMed

Camacho-Ortiz, Adrián; Gutiérrez-Delgado, Eva María; Garcia-Mazcorro, Jose F; Mendoza-Olazarán, Soraya; Martínez-Meléndez, Adrián; Palau-Davila, Laura; Baines, Simon D; Maldonado-Garza, Héctor; Garza-González, Elvira

2017-01-01

The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome. We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing. We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably

Variability, stability, and resilience of fecal microbiota in dairy cows fed whole crop corn silage.

PubMed

Tang, Minh Thuy; Han, Hongyan; Yu, Zhu; Tsuruta, Takeshi; Nishino, Naoki

2017-08-01

The microbiota of whole crop corn silage and feces of silage-fed dairy cows were examined. A total of 18 dairy cow feces were collected from six farms in Japan and China, and high-throughput Illumina sequencing of the V4 hypervariable region of 16S rRNA genes was performed. Lactobacillaceae were dominant in all silages, followed by Acetobacteraceae, Bacillaceae, and Enterobacteriaceae. In feces, the predominant families were Ruminococcaceae, Bacteroidaceae, Clostridiaceae, Lachnospiraceae, Rikenellaceae, and Paraprevotellaceae. Therefore, Lactobacillaceae of corn silage appeared to be eliminated in the gastrointestinal tract. Although fecal microbiota composition was similar in most samples, relative abundances of several families, such as Ruminococcaceae, Christensenellaceae, Turicibacteraceae, and Succinivibrionaceae, varied between farms and countries. In addition to the geographical location, differences in feeding management between total mixed ration feeding and separate feeding appeared to be involved in the variations. Moreover, a cow-to-cow variation for concentrate-associated families was demonstrated at the same farm; two cows showed high abundance of Succinivibrionaceae and Prevotellaceae, whereas another had a high abundance of Porphyromonadaceae. There was a negative correlation between forage-associated Ruminococcaceae and concentrate-associated Succinivibrionaceae and Prevotellaceae in 18 feces samples. Succinivibrionaceae, Prevotellaceae, p-2534-18B5, and Spirochaetaceae were regarded as highly variable taxa in this study. These findings help to improve our understanding of variation and similarity of the fecal microbiota of dairy cows with regard to individuals, farms, and countries. Microbiota of naturally fermented corn silage had no influence on the fecal microbiota of dairy cows.

Fecal Microbiota in Healthy Subjects Following Omnivore, Vegetarian and Vegan Diets: Culturable Populations and rRNA DGGE Profiling.

PubMed

Ferrocino, Ilario; Di Cagno, Raffaella; De Angelis, Maria; Turroni, Silvia; Vannini, Lucia; Bancalari, Elena; Rantsiou, Kalliopi; Cardinali, Gianluigi; Neviani, Erasmo; Cocolin, Luca

2015-01-01

In this study, the fecal microbiota of 153 healthy volunteers, recruited from four different locations in Italy, has been studied by coupling viable counts, on different microbiological media, with ribosomal RNA Denaturing Gradient Gel Electrophoresis (rRNA-DGGE). The volunteers followed three different diets, namely omnivore, ovo-lacto-vegetarian and vegan. The results obtained from culture-dependent and -independent methods have underlined a high level of similarity of the viable fecal microbiota for the three investigated diets. The rRNA DGGE profiles were very complex and comprised a total number of bands that varied from 67 to 64 for the V3 and V9 regions of the 16S rRNA gene, respectively. Only a few bands were specific in/of all three diets, and the presence of common taxa associated with the dietary habits was found. As far as the viable counts are concerned, the high similarity of the fecal microbiota was once again confirmed, with only a few of the investigated groups showing significant differences. Interestingly, the samples grouped differently, according to the recruitment site, thus highlighting a higher impact of the food consumed by the volunteers in the specific geographical locations than that of the type of diet. Lastly, it should be mentioned that the fecal microbiota DGGE profiles obtained from the DNA were clearly separated from those produced using RNA, thus underlining a difference between the total and viable populations in the fecal samples.

Fecal Microbiota in Healthy Subjects Following Omnivore, Vegetarian and Vegan Diets: Culturable Populations and rRNA DGGE Profiling

PubMed Central

Ferrocino, Ilario; Di Cagno, Raffaella; De Angelis, Maria; Turroni, Silvia; Vannini, Lucia; Bancalari, Elena; Rantsiou, Kalliopi; Cardinali, Gianluigi; Neviani, Erasmo; Cocolin, Luca

2015-01-01

In this study, the fecal microbiota of 153 healthy volunteers, recruited from four different locations in Italy, has been studied by coupling viable counts, on different microbiological media, with ribosomal RNA Denaturing Gradient Gel Electrophoresis (rRNA-DGGE). The volunteers followed three different diets, namely omnivore, ovo-lacto-vegetarian and vegan. The results obtained from culture-dependent and -independent methods have underlined a high level of similarity of the viable fecal microbiota for the three investigated diets. The rRNA DGGE profiles were very complex and comprised a total number of bands that varied from 67 to 64 for the V3 and V9 regions of the 16S rRNA gene, respectively. Only a few bands were specific in/of all three diets, and the presence of common taxa associated with the dietary habits was found. As far as the viable counts are concerned, the high similarity of the fecal microbiota was once again confirmed, with only a few of the investigated groups showing significant differences. Interestingly, the samples grouped differently, according to the recruitment site, thus highlighting a higher impact of the food consumed by the volunteers in the specific geographical locations than that of the type of diet. Lastly, it should be mentioned that the fecal microbiota DGGE profiles obtained from the DNA were clearly separated from those produced using RNA, thus underlining a difference between the total and viable populations in the fecal samples. PMID:26035837

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

PubMed

Paramsothy, Sudarshan; Kamm, Michael A; Kaakoush, Nadeem O; Walsh, Alissa J; van den Bogaerde, Johan; Samuel, Douglas; Leong, Rupert W L; Connor, Susan; Ng, Watson; Paramsothy, Ramesh; Xuan, Wei; Lin, Enmoore; Mitchell, Hazel M; Borody, Thomas J

2017-03-25

The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis. We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4-10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov, number NCT01896635. The trial has ended; this report presents the final analysis. From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1-11·9; p=0·021). Adverse events were reported by 32 (78

Gut microbiota injury in allogeneic haematopoietic stem cell transplantation.

PubMed

Shono, Yusuke; van den Brink, Marcel R M

2018-05-01

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to be the strongest curative immunotherapy for various malignancies (primarily, but not limited to, haematologic malignancies). However, application of allo-HSCT is limited owing to its life-threatening major complications, such as graft-versus-host disease (GVHD), relapse and infections. Recent advances in large-scale DNA sequencing technology have facilitated rapid identification of the microorganisms that make up the microbiota and evaluation of their interactions with host immunity in various diseases, including cancer. This has resulted in renewed interest regarding the role of the intestinal flora in patients with haematopoietic malignancies who have received an allo-HSCT and in whether the microbiota affects clinical outcomes, including GVHD, relapse, infections and transplant-related mortality. In this Review, we discuss the potential role of intestinal microbiota in these major complications after allo-HSCT, summarize clinical trials evaluating the microbiota in patients who have received allo-HSCT and discuss how further studies of the microbiota could inform the development of strategies that improve outcomes of allo-HSCT.

Microbiota Manipulation With Prebiotics and Probiotics in Patients Undergoing Stem Cell Transplantation

PubMed Central

Andermann, Tessa M.; Rezvani, Andrew; Bhatt, Ami S.

2016-01-01

Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that often comes at the cost of complications such as graft-versus-host disease and post-transplant infections. With improved technology to under-stand the ecosystem of microorganisms (viruses, bacteria, fungi, and microeukaryotes) that make up the gut microbiota, there is increasing evidence of the microbiota’s contribution to the development of post-transplant complications. Antibiotics have traditionally been the mainstay of microbiota-altering therapies available to physicians. Recently, interest is increasing in the use of prebiotics and probiotics to support the development and sustainability of a healthier microbiota. In this review, we will describe the evidence for the use of prebiotics and probiotics in combating microbiota dysbiosis and explore the ways in which they may be used in future research to potentially improve clinical outcomes and decrease rates of graft-versus-host disease (GVHD) and post-transplant infection. PMID:26780719

Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion Injury

PubMed Central

Rampanelli, Elena; Stroo, Ingrid; Butter, Loes M.; Teske, Gwendoline J.; Claessen, Nike; Stokman, Geurt; Florquin, Sandrine; Leemans, Jaklien C.; Dessing, Mark C.

2017-01-01

An accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gut microbiota with broad-spectrum antibiotics and performed renal ischemia-reperfusion (I/R) injury in mice. Depletion of the microbiota significantly attenuated renal damage, dysfunction, and remote organ injury and maintained tubular integrity after renal I/R injury. Gut flora–depleted mice expressed lower levels of F4/80 and chemokine receptors CX3CR1 and CCR2 in the F4/80+ renal resident macrophage population and bone marrow (BM) monocytes than did control mice. Additionally, compared with control BM monocytes, BM monocytes from gut flora–depleted mice had decreased migratory capacity toward CX3CL1 and CCL2 ligands. To study whether these effects were driven by depletion of the microbiota, we performed fecal transplants in antibiotic-treated mice and found that transplant of fecal material from an untreated mouse abolished the protective effect of microbiota depletion upon renal I/R injury. In conclusion, we show that depletion of gut microbiota profoundly protects against renal I/R injury by reducing maturation status of F4/80+ renal resident macrophages and BM monocytes. Therefore, dampening the inflammatory response by targeting microbiota-derived mediators might be a promising therapy against I/R injury. PMID:27927779

Characteristics of Fecal and Mucosa-Associated Microbiota in Chinese Patients With Inflammatory Bowel Disease

PubMed Central

Chen, Liping; Wang, Wei; Zhou, Rui; Ng, Siew C.; Li, Jin; Huang, Meifang; Zhou, Feng; Wang, Xin; Shen, Bo; A. Kamm, Michael; Wu, Kaichun; Xia, Bing

2014-01-01

Abstract The intestinal microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD), and geographical and genetic backgrounds impact the composition of the intestinal microbiota. However, there is a lack of evidence regarding the overall changes and characteristics of fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) in Chinese patients with IBD. We recruited 26 patients with Crohn’s disease (CD), 46 patients with ulcerative colitis (UC), and 21 healthy individuals; we collected matched fresh fecal and mucosal samples from the same subjects. The microbial communities were studied by 454-pyrosequencing. Community-wide changes in FAM and MAM were observed in patients with IBD. The proportion of several butyrate-producing bacteria, such as of the genera Roseburia, Coprococcus, and Ruminococcus were significantly reduced, whereas the pathogens Escherichia-Shigella and Enterococcus were prevalent in patients with IBD. FAM and MAM were similar between CD and UC. FAM differed from MAM in healthy individuals and patients with UC. In conclusion, the compositions of FAM and MAM were altered in patients with IBD. The reduction of butyrate-producing bacteria and the increase in opportunistic pathogens might be associated with the pathogenesis of IBD. PMID:25121355

Alterations in the Fecal Microbiota of Patients with HIV-1 Infection: An Observational Study in A Chinese Population

PubMed Central

Ling, Zongxin; Jin, Changzhong; Xie, Tiansheng; Cheng, Yiwen; Li, Lanjuan; Wu, Nanping

2016-01-01

The available evidence suggests that alterations in gut microbiota may be tightly linked to the increase in microbial translocation and systemic inflammation in patients with human immunodeficiency virus 1 (HIV-1) infection. We profiled the fecal microbiota as a proxy of gut microbiota by parallel barcoded 454-pyrosequencing in 67 HIV-1-infected patients (32 receiving highly active antiretroviral therapy [HAART] and 35 HAART naïve) and 16 healthy controls from a Chinese population. We showed that α-diversity indices did not differ significantly between the healthy control and HIV-1-infected patients. The ratio of Firmicutes/Bacteroidetes increased significantly in HIV-1-infected patients. Several key bacterial phylotypes, including Prevotella, were prevalent in HIV-1-infected patients; whereas Phascolarctobacterium, Clostridium XIVb, Dialister and Megamonas were significantly correlated with systemic inflammatory cytokines. After short-term, effective HAART, the viral loads of HIV-1 were reduced; however, the diversity and composition of the fecal microbiota were not completely restored. and the dysbiosis remained among HIV-1-infected subjects undergoing HAART. Our detailed analysis demonstrated that dysbiosis of fecal microbiota might play an active role in HIV-1 infection. Thus, new insights may be provided into therapeutics that target the microbiota to attenuate the progression of HIV disease and to reduce the risk of gut-linked disease in HIV-1-infected patients. PMID:27477587

The gut microbiota: A treasure for human health.

PubMed

Li, Daotong; Wang, Pan; Wang, Pengpu; Hu, Xiaosong; Chen, Fang

2016-11-15

The interplay between the host and host-associated gut microbiota is an area of increasing interest during the recent decade. From young infants to elderly people, from primitive tribes to modern societies, accumulating evidence has suggested the association of critical physiological roles of gut microbiota in the pathogenesis of a variety of human metabolic, immunological and neurological diseases. Importantly, it appears that the relationship between the gut microbiota and disease is bidirectional, instead of causal or consequential. Personalized nutritional and therapeutic strategies targeting the gut microbiota such as prebiotics, probiotics, drugs and fecal microbiota transplantation may create a new era in the human health. Copyright © 2016 Elsevier Inc. All rights reserved.

Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

PubMed Central

Khoruts, Alexander; Rank, Kevin M.; Newman, Krista M.; Viskocil, Kimberly; Vaughn, Byron P.; Hamilton, Matthew J.; Sadowsky, Michael J.

2017-01-01

BACKGROUND & AIMS A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure. METHODS We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients’ right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT. RESULTS Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI. CONCLUSIONS Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic

Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis.

PubMed

Kassam, Zain; Lee, Christine H; Yuan, Yuhong; Hunt, Richard H

2013-04-01

The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI. An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups. Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I(2

Fecal microbiota of lambs fed purple prairie clover (Dalea purpurea Vent.) and alfalfa (Medicago sativa).

PubMed

Huang, Qianqian; Holman, Devin B; Alexander, Trevor; Hu, Tianming; Jin, Long; Xu, Zhongjun; McAllister, Tim A; Acharya, Surya; Zhao, Guoqi; Wang, Yuxi

2018-01-01

The present study assessed the effect of purple prairie clover (PPC) and PPC condensed tannins (CT) on the fecal microbiota of lambs using high-throughput 16S rRNA gene pyrosequencing. A total of 18 individual lambs were randomly divided into three groups and fed either green chop alfalfa (Alf), a 40:60 (DM basis; Mix) mixture of Alf and PPC, or Mix supplemented with polyethylene glycol (Mix-P) for 18 days. Fecal samples were collected on days 13 through 18 using digital rectal retrieval. The DNA of fecal samples was extracted and the microbial 16S rRNA gene amplicons were sequenced using 454 pyrosequencing. Regardless of diet, the bacterial community was dominated by Firmicutes and Bacteroidetes with many sequences unclassified at the genus level. Forage type and CT had no effect on the fecal microbial composition at the phylum level or on α-diversity. Compared to the Alf diet, the Mix diet reduced the relative abundance of Akkermansia (P = 0.03) and Asteroleplasma (P = 0.05). Fecal microbial populations in Alf and Mix-P clustered separately from each other when assessed using unweighted UniFrac (P < 0.05). These results indicate that PPC CT up to 36 g/kg DM in the diet had no major effect on fecal microbial flora at the phyla level and exerted only minor effects on the genera composition of fecal microbiota in lambs.

Fecal Microbiota Therapy With a Focus on Clostridium difficile Infection.

PubMed

Brandt, Lawrence J

2017-10-01

There has been a paradigm shift in our view of bacteria away from their role as just pathogens. We now have a deepening appreciation of their critical influences in our health maintenance, including energy harvest, metabolism, intestinal development, cell proliferation, nervous system and immune function, as well as their role to protect against intestinal and other infections. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and nongastrointestinal diseases but particularly with Clostridium difficile infection (CDI). Although such association does not imply causation, it has been shown that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic and recurring CDI and that FMT can effect a seemingly safe and rapidly effective cure for most patients with CDI so treated. FMT has been used to treat a wide range of other diseases, although conclusions about efficacy in any disease other than CDI must await appropriate well-designed trials. More work needs to be conducted with FMT, especially to evaluate and ensure its long-term safety. Future studies are likely to narrow the spectrum of organisms that needs to be given to patients to cure CDI, and perhaps other diseases, and to elucidate the mechanisms whereby such therapeutic benefit occurs. FMT is but the first step in this journey.

Fecal concentrations of bacterially derived vitamin K forms are associated with gut microbiota composition but not plasma or fecal cytokine concentrations in healthy adults.

PubMed

Karl, J Philip; Meydani, Mohsen; Barnett, Junaidah B; Vanegas, Sally M; Barger, Kathryn; Fu, Xueyan; Goldin, Barry; Kane, Anne; Rasmussen, Helen; Vangay, Pajau; Knights, Dan; Jonnalagadda, Satya S; Saltzman, Edward; Roberts, Susan B; Meydani, Simin N; Booth, Sarah L

2017-10-01

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined. Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation. Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8. Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation

Modulation of gut microbiota and increase in fecal water content in mice induced by administration of Lactobacillus kefiranofaciens DN1.

PubMed

Jeong, Dana; Kim, Dong-Hyeon; Kang, Il-Byeong; Kim, Hyunsook; Song, Kwang-Young; Kim, Hong-Seok; Seo, Kun-Ho

2017-02-22

Lactobacillus kefiranofaciens is the key probiotic bacterium in kefir. In this study, we investigated the effects of oral consumption of L. kefiranofaciens on the fecal quality and intestinal microbiota of mice. Four-week-old Balb/c mice were divided into two groups (n = 8 each) and administered 0.2 mL of saline (control group) or saline containing 2 × 10 8 cfu L. kefiranofaciens DN1 (LKF_DN1 group) for two weeks. At the end of the experiment, their fecal samples were collected and the fecal quality and microbiota were assessed. The LKF_DN1 group exhibited higher total fecal weight and fecal weight per stool sample than the control group (p < 0.05). Interestingly, the fecal water content was significantly higher in the fecal samples of the LKF_DN1 group than in those of the control group (p < 0.05). The numbers of total bacteria, Firmicutes, Bacteroidetes, Lactobacillus, and Prevotella were significantly higher in the LKF_DN1 group than in the control group (p < 0.05). In contrast, the number of opportunistic pathogens, including Proteobacteria and Enterobacteriaceae, and the percentage of genus Clostridium among the total bacteria were significantly reduced in the LKF_DN1 group (p < 0.05). Our data suggest that regular L. kefiranofaciens DN1 administration could alleviate constipation and improve gut microbiota.

Cost Averted With Timely Fecal Microbiota Transplantation in the Management of Recurrent Clostridium difficile Infection in Alberta, Canada.

PubMed

Waye, Arianna; Atkins, Kerry; Kao, Dina

2016-10-01

Fecal microbiota transplantation (FMT) is highly effective in treating recurrent Clostridium difficile infection (RCDI). However, the ideal timing for offering FMT remains to be determined. Furthermore, the direct medical costs averted with timely FMT have not been examined. A retrospective review of the Edmonton FMT program database included patients who received FMT for RCDI (October 2012 to September 2014). They were divided into 2 groups: those who received FMT after 2 recurrences (the timely FMT group) and those who received FMT after at least 3 recurrences (the delayed FMT group). The primary outcome was the difference in direct medical costs related to hospital admissions and emergency room visits due to CDI between the 2 groups. The secondary outcomes were RCDI cure rate and duration of RCDI in each group. A total of 75 patients were included: 30 received timely FMT, whereas 45 received delayed FMT. The mean difference in hospital length of stay and emergency room visits related to CDI were 13.8 days shorter and 1.3 visits fewer with timely FMT, associated with a mean cost saving of $29,842 per patient. Sensitivity analysis was performed to examine the effect of outliers and comorbities on the differential costs, and it was found that the differences in average cost per patient were more pronounced in those with Charlson comorbidity index ≥3 compared with those with scores of 0 to 2. The cure rate was 94% (timely FMT group) and 93% (delayed FMT group). The mean duration of RCDI was 109 days (timely FMT group) and 281 days (delayed FMT group). Timely FMT can provide significant cost savings to health-care systems, especially for patients with multiple comorbidities.

Gut microbiota dysbiosis contributes to the development of hypertension.

PubMed

Li, Jing; Zhao, Fangqing; Wang, Yidan; Chen, Junru; Tao, Jie; Tian, Gang; Wu, Shouling; Liu, Wenbin; Cui, Qinghua; Geng, Bin; Zhang, Weili; Weldon, Ryan; Auguste, Kelda; Yang, Lei; Liu, Xiaoyan; Chen, Li; Yang, Xinchun; Zhu, Baoli; Cai, Jun

2017-02-01

Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases. Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown. To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice. Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations. Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension. The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis. And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately. Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated. Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension. And the significance of early intervention for pre-hypertension was emphasized.

Vertically transmitted fecal IgA levels distinguish extra-chromosomal phenotypic variation

PubMed Central

Wallace, Meghan A.; D, Carey-Ann; Burnham; Virgin, Herbert W.; Stappenbeck, Thaddeus S.

2014-01-01

Summary The proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control1-5. In many cases, the microbiota is the presumed culprit of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice6,7. In conventionally raised mice, the microbiome is transmitted from the dam2,8,9. Here we show that microbially–driven dichotomous fecal IgA levels in WT mice within the same facility mimic the effects of chromosomal mutations. We observed in multiple facilities that vertically-transmissible bacteria in IgA-Low mice dominantly lowered fecal IgA levels in IgA-High mice after cohousing or fecal transplantation. In response to injury, IgA-Low mice showed increased damage that was transferable by fecal transplantation and driven by fecal IgA differences. We found that bacteria from IgA-Low mice degraded the secretory component (SC) of SIgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose fecal IgA as one marker of microbial variability and conclude that cohousing and/or fecal transplantation enables analysis of progeny from different dams. PMID:25686606

Potential of fecal microbiota for early-stage detection of colorectal cancer

PubMed Central

Zeller, Georg; Tap, Julien; Voigt, Anita Y; Sunagawa, Shinichi; Kultima, Jens Roat; Costea, Paul I; Amiot, Aurélien; Böhm, Jürgen; Brunetti, Francesco; Habermann, Nina; Hercog, Rajna; Koch, Moritz; Luciani, Alain; Mende, Daniel R; Schneider, Martin A; Schrotz-King, Petra; Tournigand, Christophe; Tran Van Nhieu, Jeanne; Yamada, Takuji; Zimmermann, Jürgen; Benes, Vladimir; Kloor, Matthias; Ulrich, Cornelia M; von Knebel Doeberitz, Magnus; Sobhani, Iradj; Bork, Peer

2014-01-01

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism. PMID:25432777

Comparative Analysis of Fecal Microbiota in Infants with and without Eczema

PubMed Central

Hong, Pei-Ying; Lee, Bee Wah; Aw, Marion; Shek, Lynette Pei Chi; Yap, Gaik Chin; Chua, Kaw Yan; Liu, Wen-Tso

2010-01-01

Eczema is a chronic form of childhood disorder that is gaining in prevalence in affluent societies. Previous studies hypothesized that the development of eczema is correlated with changes in microbial profile and composition of early life endemic microbiota, but contradictory conclusions were obtained, possibly due to the lack of minimization of apparent non-health related confounders (e.g., age, antibiotic consumption, diet and mode of delivery). In this study, we recruited seven caesarean-delivered and total formula-fed infants, and comparatively examined the early-life endemic microbiota in these infants with and without eczema. Using 16S pyrosequencing, infants' fecal microbiota were observed to comprise Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes as the four main phyla, and the presence and absence of specific populations within these four phyla are primarily mediated by ageing. Quantitative analysis of bacterial targets on a larger sample size (n = 36 at 1, 3, and 12 months of age) revealed that the abundances of Bifidobacterium and Enterobacteriaceae were different among caesarean-delivered infants with and without eczema, and the bacterial targets may be potential biomarkers that can correlate to the health status of these infants. Our overall findings suggest that the minimization of possible confounders is essential prior to comparative evaluation and correlation of fecal microbiota to health status, and that stool samples collected from caesarean-delivered infants at less than 1 year of age may represent a good cohort to study for potential biomarkers that can distinguish infants with eczema from those without. These findings would greatly facilitate future efforts in understanding the possible pathogenesis behind certain bacterial targets, and may lead to a timely intervention that reduces the occurrence of early life eczema and possibly allergic disorders in later life. PMID:20376357

Changes in the equine fecal microbiota associated with the use of systemic antimicrobial drugs.

PubMed

Costa, Marcio C; Stämpfli, Henry R; Arroyo, Luis G; Allen-Vercoe, Emma; Gomes, Roberta G; Weese, J Scott

2015-02-03

The intestinal tract is a rich and complex environment and its microbiota has been shown to have an important role in health and disease in the host. Several factors can cause disruption of the normal intestinal microbiota, including antimicrobial therapy, which is an important cause of diarrhea in horses. This study aimed to characterize changes in the fecal bacterial populations of healthy horses associated with the administration of frequently used antimicrobial drugs. Twenty-four adult mares were assigned to receive procaine penicillin intramuscularly (IM), ceftiofur sodium IM, trimethoprim sulfadiazine (TMS) orally or to a control group. Treatment was given for 5 consecutive days and fecal samples were collected before drug administration (Day 1), at the end of treatment (Days 5), and on Days 14 and 30 of the trial. High throughput sequencing of the V4 region of the 16S rRNA gene was performed using an Illumina MiSeq sequencer. Significant changes of population structure and community membership were observed after the use of all drugs. TMS caused the most marked changes on fecal microbiota even at higher taxonomic levels including a significant decrease of richness and diversity. Those changes were mainly due to a drastic decrease of Verrucomicrobia, specifically the "5 genus incertae sedis". Changes in structure and membership caused by antimicrobial administration were specific for each drug and may be predictable. Twenty-five days after the end of treatment, bacterial profiles were more similar to pre-treatment patterns indicating a recovery from changes caused by antimicrobial administration, but differences were still evident, especially regarding community membership. The use of systemic antimicrobials leads to changes in the intestinal microbiota, with different and specific responses to different antimicrobials. All antimicrobials tested here had some impact on the microbiota, but TMS significantly reduced bacterial species richness and diversity and

Effect of Dietary Starch Source and Concentration on Equine Fecal Microbiota

PubMed Central

Harlow, Brittany E.; Lawrence, Laurie M.; Hayes, Susan H.; Crum, Andrea; Flythe, Michael D.

2016-01-01

Starch from corn is less susceptible to equine small intestinal digestion than starch from oats, and starch that reaches the hindgut can be utilized by the microbiota. The objective of the current study was to examine the effects of starch source on equine fecal microbiota. Thirty horses were assigned to treatments: control (hay only), HC (high corn), HO (high oats), LC (low corn), LO (low oats), and LW (low pelleted wheat middlings). Horses received an all-forage diet (2 wk; d -14 to d -1) before the treatment diets (2 wk; d 1 to 14). Starch was introduced gradually so that horses received 50% of the assigned starch amount (high = 2 g starch/kg BW; low = 1 g starch/kg BW) by d 4 and 100% by d 11. Fecal samples were obtained at the end of the forage-only period (S0; d -2), and on d 6 (S1) and d 13 (S2) of the treatment period. Cellulolytics, lactobacilli, Group D Gram-positive cocci (GPC), lactate-utilizers and amylolytics were enumerated. Enumeration data were log transformed and analyzed by repeated measures ANOVA. There were sample day × treatment interactions (P < 0.0001) for all bacteria enumerated. Enumerations from control horses did not change during the sampling period (P > 0.05). All treatments except LO resulted in increased amylolytics and decreased cellulolytics, but the changes were larger in horses fed corn and wheat middlings (P < 0.05). Feeding oats resulted in increased lactobacilli and decreased GPC (P < 0.05), while corn had the opposite effects. LW had increased lactobacilli and GPC (P < 0.05). The predominant amylolytic isolates from HC, LC and LW on S2 were identified by 16S RNA gene sequencing as Enterococcus faecalis, but other species were found in oat fed horses. These results demonstrate that starch source can have a differential effect on the equine fecal microbiota. PMID:27128793

Effect of daily intake of pomegranate juice on fecal microbiota and feces metabolites from healthy volunteers.

PubMed

Mosele, Juana I; Gosalbes, María-José; Macià, Alba; Rubió, Laura; Vázquez-Castellanos, Jorge F; Jiménez Hernández, Nuria; Moya, Andrés; Latorre, Amparo; Motilva, María-José

2015-10-01

The purpose of the study was to evaluate the effect, regarding the metabolic and microbial profile of feces, of diet supplementation of healthy adults with pomegranate juice (PJ). Twelve healthy adults were recruited to the study, which consisted of the intake of 200 mL/day of PJ during 4 weeks. Feces were collected before and after the supplementation with PJ. Metabolites (phenolic catabolites, short-chain fatty acids, and fecal steroids) and microbial profile were analyzed at baseline and at 4 weeks. Fecal phenolic metabolites, 3-phenylpropionic acid, catechol, hydroxytyrosol, and urolithin A, showed a significant increase in their concentration after supplementation with PJ. Among fecal steroids, parallel to the significant increase of cholesterol concentration, a significant decrease of coprostanol was observed. Although no significant changes in the microbiota profile were observed, different relationships between initial microbiota and the metabolites produced were found. Catechol showed positive and negative correlation with Oscillospora and Paraprevotella genera, respectively, and 3-phenylpropionic acid was positively correlated with Odoribacter genus. Inclusion of PJ in the diet did not significantly alter the gut microbiota composition in healthy adults, but the individual bacterial composition could contribute to the generation of potential health-promoting phenolic metabolites. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extrusion of barley and oat influence the fecal microbiota and SCFA profile of growing pigs.

PubMed

Moen, Birgitte; Berget, Ingunn; Rud, Ida; Hole, Anastasia S; Kjos, Nils Petter; Sahlstrøm, Stefan

2016-02-01

The effect of extrusion of barley and oat on the fecal microbiota and the formation of SCFA was evaluated using growing pigs as model system. The pigs were fed a diet containing either whole grain barley (BU), oat groat (OU), or their respective extruded samples (BE and OE). 454 pyrosequencing showed that the fecal microbiota of growing pigs was affected by both extrusion and grain type. Extruded grain resulted in lower bacterial diversity and enrichment in operational taxonomic units (OTUs) affiliated with members of the Streptococcus, Blautia and Bulleidia genera, while untreated grain showed enrichment in OTUs affiliated with members of the Bifidobacterium and Lactobacillus genera, and the butyrate-producing bacteria Butyricicoccus, Roseburia, Coprococcus and Pseudobutyrivibrio. Untreated grain resulted in a significant increase of n-butyric, i-valeric and n-valeric acid, which correlated with an increase of Bifidobacterium and Lactobacillus. This is the first study showing that cereal extrusion affects the microbiota composition and diversity towards a state generally thought to be less beneficial for health, as well as less amounts of beneficial butyric acid.

Shifts in the Fecal Microbiota Associated with Adenomatous Polyps.

PubMed

Hale, Vanessa L; Chen, Jun; Johnson, Stephen; Harrington, Sean C; Yab, Tracy C; Smyrk, Thomas C; Nelson, Heidi; Boardman, Lisa A; Druliner, Brooke R; Levin, Theodore R; Rex, Douglas K; Ahnen, Dennis J; Lance, Peter; Ahlquist, David A; Chia, Nicholas

2017-01-01

Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547). Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H 2 S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer. This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota. Cancer Epidemiol Biomarkers Prev; 26(1); 85-94. ©2016 AACR. ©2016 American Association for Cancer Research.

Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease.

PubMed

Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

2015-01-01

Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.

Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease

PubMed Central

Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

2015-01-01

Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy. PMID:25531678

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis.

PubMed

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W; Krause, Denis O; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis

PubMed Central

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W.; Krause, Denis O.; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that

Human Gut Microbiota: Toward an Ecology of Disease

PubMed Central

Selber-Hnatiw, Susannah; Rukundo, Belise; Ahmadi, Masoumeh; Akoubi, Hayfa; Al-Bizri, Hend; Aliu, Adelekan F.; Ambeaghen, Tanyi U.; Avetisyan, Lilit; Bahar, Irmak; Baird, Alexandra; Begum, Fatema; Ben Soussan, Hélène; Blondeau-Éthier, Virginie; Bordaries, Roxane; Bramwell, Helene; Briggs, Alicia; Bui, Richard; Carnevale, Matthew; Chancharoen, Marisa; Chevassus, Talia; Choi, Jin H.; Coulombe, Karyne; Couvrette, Florence; D'Abreau, Samantha; Davies, Meghan; Desbiens, Marie-Pier; Di Maulo, Tamara; Di Paolo, Sean-Anthony; Do Ponte, Sabrina; dos Santos Ribeiro, Priscyla; Dubuc-Kanary, Laure-Anne; Duncan, Paola K.; Dupuis, Frédérique; El-Nounou, Sara; Eyangos, Christina N.; Ferguson, Natasha K.; Flores-Chinchilla, Nancy R.; Fotakis, Tanya; Gado Oumarou H D, Mariam; Georgiev, Metodi; Ghiassy, Seyedehnazanin; Glibetic, Natalija; Grégoire Bouchard, Julien; Hassan, Tazkia; Huseen, Iman; Ibuna Quilatan, Marlon-Francis; Iozzo, Tania; Islam, Safina; Jaunky, Dilan B.; Jeyasegaram, Aniththa; Johnston, Marc-André; Kahler, Matthew R.; Kaler, Kiranpreet; Kamani, Cedric; Karimian Rad, Hessam; Konidis, Elisavet; Konieczny, Filip; Kurianowicz, Sandra; Lamothe, Philippe; Legros, Karina; Leroux, Sebastien; Li, Jun; Lozano Rodriguez, Monica E.; Luponio-Yoffe, Sean; Maalouf, Yara; Mantha, Jessica; McCormick, Melissa; Mondragon, Pamela; Narayana, Thivaedee; Neretin, Elizaveta; Nguyen, Thi T. T.; Niu, Ian; Nkemazem, Romeo B.; O'Donovan, Martin; Oueis, Matthew; Paquette, Stevens; Patel, Nehal; Pecsi, Emily; Peters, Jackie; Pettorelli, Annie; Poirier, Cassandra; Pompa, Victoria R.; Rajen, Harshvardhan; Ralph, Reginald-Olivier; Rosales-Vasquez, Josué; Rubinshtein, Daria; Sakr, Surya; Sebai, Mohammad S.; Serravalle, Lisa; Sidibe, Fily; Sinnathurai, Ahnjana; Soho, Dominique; Sundarakrishnan, Adithi; Svistkova, Veronika; Ugbeye, Tsolaye E.; Vasconcelos, Megan S.; Vincelli, Michael; Voitovich, Olga; Vrabel, Pamela; Wang, Lu; Wasfi, Maryse; Zha, Cong Y.; Gamberi, Chiara

2017-01-01

Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics. PMID:28769880

Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon.

PubMed

Cui, Huantian; Cai, Yuzi; Wang, Li; Jia, Beitian; Li, Junchen; Zhao, Shuwu; Chu, Xiaoqian; Lin, Jin; Zhang, Xiaoyu; Bian, Yuhong; Zhuang, Pengwei

2018-01-01

Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode , and Berberis , has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium , and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.

Salivary and fecal microbiota and metabolome of celiac children under gluten-free diet.

PubMed

De Angelis, Maria; Vannini, Lucia; Di Cagno, Raffaella; Cavallo, Noemi; Minervini, Fabio; Francavilla, Ruggiero; Ercolini, Danilo; Gobbetti, Marco

2016-12-19

Celiac disease (CD) is an inflammatory autoimmune disorder resulting from the combination of genetic predisposition and gluten ingestion. A life-long gluten free diet (GFD) is the only therapeutic approach. Dysbiosis, which can precede the CD pathogenesis and/or persist when subjects are on GFD, is reviewed and discussed. Salivary microbiota and metabolome differed between healthy and celiac children treated under GFD (T-CD) for at least two years. The type of GFD (African- vs Italian-style) modified the microbiota and metabolome of Saharawi T-CD children. Different studies showed bacterial dysbiosis at duodenal and/or fecal level of patients with active untreated CD (U-CD) and T-CD compared to healthy subjects. The ratio of protective anti-inflammatory bacteria such as Lactobacillus-Bifidobacterium to potentially harmful Bacteroides-Enterobacteriaceae was the lowest in U-CD and T-CD children. In agreement with dysbiosis, serum, fecal and urinary metabolome from U-CD and T-CD patients showed altered levels of free amino acids and volatile organic compounds. However, consensus across studies defining specific bacteria and metabolites in U-CD or T-CD patients is still lacking. Future research efforts are required to determine the relationships between CD and oral and intestinal microbiotas to improve the composition of GFD for restoring the gut dysbiosis as a preventative or therapeutic approach for CD. Copyright © 2016 Elsevier B.V. All rights reserved.

Composition and metabolism of fecal microbiota from normal and overweight children are differentially affected by melibiose, raffinose and raffinose-derived fructans.

PubMed

Adamberg, Kaarel; Adamberg, Signe; Ernits, Karin; Larionova, Anneli; Voor, Tiia; Jaagura, Madis; Visnapuu, Triinu; Alamäe, Tiina

2018-06-20

The aim of the study was to investigate the metabolism of non-digestible oligo- and polysaccharides by fecal microbiota, using isothermal microcalorimetry. The five tested substrates were raffinose, melibiose, a mixture of oligo- and polysaccharides produced from raffinose by levansucrase, levan synthesized from raffinose, and levan from timothy grass. Two inocula were comprised of pooled fecal samples from overweight or normal-weight children, from healthy adult volunteers and a pure culture of Bacteroides thetaiotaomicron as a reference bacterium for colon microbiota. The growth was analyzed based on the heat evolution curves, and the production of organic acids and gases. Taxonomic profiles of the microbiota were assessed by 16S rDNA sequencing. Raffinose and melibiose promoted the growth of bifidobacteria in all fecal pools. Several pool-specific substrate-related responses to raffinose and melibiose were revealed. Lactate-producing bacteria (Streptococcus and Enterococcus) became enriched in the pool of overweight children resulting in lactic acid as the major fermentation product on short saccharides. Acetic and butyric acids were prevalent at fermentation in the normal-weight pool coinciding with the enrichment of Catenibacterium. In the adult pool, the specific promotion of Bacteroides and Lachnospiraceae by levans was disclosed. In the fecal pool of normal-weight children, levans stimulated the growth of Senegalimassilia and Lachnoclostridium and this particular pool also showed the highest maximum heat production rate at levan fermentation. Levans and raffinose-derived oligosaccharides, but not raffinose and melibiose were completely fermented by a pure culture of Bacteroides thetaiotaomicron. The main conclusion from the study is that fecal microbiota of normal and overweight children have different compositions and they respond in specific manners to non-digestible oligo- and polysaccharides: raffinose, melibiose, raffinose-derived oligosaccharides and

Trametes versicolor extract modifies human fecal microbiota composition in vitro.

PubMed

Yu, Zhuo-Teng; Liu, Bo; Mukherjee, Purna; Newburg, David S

2013-06-01

Trametes versicolor is a mushroom used as a traditional Chinese medicine (Yun-zhi) for a wide array of seemingly disparate conditions. We hypothesized that many of its multiple purported activities could be mediated through stimulation of beneficial mutualist components of the microbiota. Human fecal microbiota was cultured anaerobically to determine its ability to ferment a common extract of T. versicolor, designated polysaccharide peptide (PSP), and the ability of PSP to alter the composition of the microbial community. The presence of PSP and fructooligosaccharides (FOS, a common prebiotic) in the medium, but not cellulose, significantly increased levels of Bifidobacterium spp. PSP also elevated Lactobacillus spp., while reducing Clostridium spp., Staphylococcus spp. and Enterococcus spp. Levels of Streptococcus spp., Bacteroides spp. and Escherichia did not significantly change. Fermentation of PSP increased the concentration of organic acids (lactate and short-chain fatty acids), decreased the pH, and induced β-galactosidase and β-glucosidase activities. The genera of the human microbiota that are promoted by FOS and other prebiotics are also stimulated by the Trametes versicolor extract, PSP. Thus, Trametes versicolor, a common East Asian botanical, contains putative prebiotic agents that alter human gut microbiota and pH. This prebiotic-like activity may help explain some of the plethora of the health benefits attributed to this traditional Chinese medicine.

Lactobacillus paracasei A survives gastrointestinal passage and affects the fecal microbiota of healthy infants.

PubMed

Marzotto, Marta; Maffeis, Claudio; Paternoster, Thomas; Ferrario, Rossano; Rizzotti, Lucia; Pellegrino, Maristella; Dellaglio, Franco; Torriani, Sandra

2006-11-01

This study focuses on the potentiality of a putative probiotic strain, Lactobacillus paracasei A, to survive gastrointestinal (GI) passage and modulate the resident microbiota of healthy infants. In a placebo-controlled study, 26 children aged 12-24 months received 100 g/day of either fermented milk containing strain A or pasteurized yogurt for four weeks. Fecal samples were analyzed before starting the administration, after 1, 3 and 4 weeks of consumption and after washout. The fate of strain A was followed by means of a newly developed PCR targeting a strain-specific genomic marker. The composition and dynamics of fecal microbial communities during the study were analyzed by culturing on selective media and by the PCR-denaturing gradient gel electrophoresis (DGGE) technique using universal and group-specific (Lactobacillus and Bifidobacterium) primers. The variation in enzymatic activities in infant feces during probiotic consumption was also analyzed. Strain A survived in fecal samples in most (92%) of the infants examined after 1 week of consumption, and temporarily dominated the intestinal Lactobacillus community. The administration of L. paracasei A led to a significant increment in the Lactobacillus population, while a moderate effect upon the main bacterial groups in the GI ecosystem was observed. Strain A also affected the diversity of the Lactobacillus and Bifidobacterium populations. The fecal bacterial structure of 1 - 2-year-old infants seems to combine neonate and adult-like features. The microbiota of these subjects promptly responded to probiotic consumption, later restoring the endogenous equilibrium.

Allergy associations with the adult fecal microbiota: Analysis of the American Gut Project.

PubMed

Hua, Xing; Goedert, James J; Pu, Angela; Yu, Guoqin; Shi, Jianxin

2016-01-01

Alteration of the gut microbial population (dysbiosis) may increase the risk for allergies and other conditions. This study sought to clarify the relationship of dysbiosis with allergies in adults. Publicly available American Gut Project questionnaire and fecal 16S rRNA sequence data were analyzed. Fecal microbiota richness (number of observed species) and composition (UniFrac) were used to compare adults with versus without allergy to foods (peanuts, tree nuts, shellfish, other) and non-foods (drug, bee sting, dander, asthma, seasonal, eczema). Logistic and Poisson regression models adjusted for potential confounders. Odds ratios and 95% confidence intervals (CI) were calculated for lowest vs highest richness tertile. Taxonomy associations considered 122 non-redundant taxa (of 2379 total taxa) with ≥ 0.1% mean abundance. Self-reported allergy prevalence among the 1879 participants (mean age, 45.5 years; 46.9% male) was 81.5%, ranging from 2.5% for peanuts to 40.5% for seasonal. Fecal microbiota richness was markedly lower with total allergies (P = 10(-9)) and five particular allergies (P ≤ 10(-4)). Richness odds ratios were 1.7 (CI 1.3-2.2) with seasonal, 1.8 (CI 1.3-2.5) with drug, and 7.8 (CI 2.3-26.5) with peanut allergy. These allergic participants also had markedly altered microbial community composition (unweighted UniFrac, P = 10(-4) to 10(-7)). Total food and non-food allergies were significantly associated with 7 and 9 altered taxa, respectively. The dysbiosis was most marked with nut and seasonal allergies, driven by higher Bacteroidales and reduced Clostridiales taxa. American adults with allergies, especially to nuts and seasonal pollen, have low diversity, reduced Clostridiales, and increased Bacteroidales in their gut microbiota. This dysbiosis might be targeted to improve treatment or prevention of allergy.

The influence of the microbiota on the immune response to transplantation

PubMed Central

Bartman, Caroline; Chong, Anita S.; Alegre, Maria-Luisa

2015-01-01

Purpose of review In the past decade, appreciation of the important effects of commensal microbes on immunity has grown exponentially. The effect of the microbiota on transplantation has only recently begun to be explored; however, our understanding of the mechanistic details of host-microbe interactions is still lacking. Recent findings It has become clear that transplantation is associated with changes in the microbiota in many different settings although what clinical events and therapeutic interventions contribute to these changes remains to be parsed out. Research groups have begun to identify associations between specific communities of organisms and transplant outcomes but it remains to be established whether microbial changes precede or follow transplant rejection episodes. Finally, results from continuing exploration of basic mechanisms by which microbial communities affect innate and adaptive immunity in various animal models of disease continues to inform research on the microbiota’s effects on immune responses against transplanted organs. Summary Commensal microbes may alter immune responses to organ transplantation, but direct experiments are only beginning in the field to identify species and immune pathways responsible for these putative effects. PMID:25563985

Influence of Novel Highly Pathogenic Avian Influenza A (H5N1) Virus Infection on Migrating Whooper Swans Fecal Microbiota.

PubMed

Zhao, Na; Wang, Supen; Li, Hongyi; Liu, Shelan; Li, Meng; Luo, Jing; Su, Wen; He, Hongxuan

2018-01-01

The migration of wild birds plays an important role in the transmission and spread of H5 highly pathogenic avian influenza (HPAI) virus, posing a severe risk to animal and human health. Substantial evidence suggests that altered gut microbial community is implicated in the infection of respiratory influenza virus. However, the influence of H5N1 infection in gut microbiota of migratory birds remains unknown. In January 2015, a novel recombinant H5N1 virus emerged and killed about 100 migratory birds, mainly including whooper swans in Sanmenxia Reservoir Area of China. Here, we describe the first fecal microbiome diversity study of H5N1-infected migratory birds. By investigating the influence of H5N1 infection on fecal bacterial communities in infected and uninfected individuals, we found that H5N1 infection shaped the gut microbiota composition by a difference in the dominance of some genera, such as Aeromonas and Lactobacillus . We also found a decreased α diversity and increased β diversity in infectious individuals. Our results highlight that increases in changes in pathogen-containing gut communities occur when individuals become infected with H5N1. Our study may provide the first evidence that there are statistical association among H5N1 presence and fecal microbiota compositional shifts, and properties of the fecal microbiota may serve as the risk of gut-linked disease in migrates with H5N1 and further aggravate the disease transmission.

Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats.

PubMed

Forsgård, Richard A; Marrachelli, Vannina G; Korpela, Katri; Frias, Rafael; Collado, Maria Carmen; Korpela, Riitta; Monleon, Daniel; Spillmann, Thomas; Österlund, Pia

2017-08-01

Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance ( 1 H-NMR). Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH 3 ) 3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids. Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.

Current status of the microbiome in renal transplantation.

PubMed

Ahmad, Sarwat; Bromberg, Jonathan S

2016-11-01

An imbalance between pathogenic and protective microbiota characterizes dysbiosis. Presence of dysbiosis may affect immunity, tolerance, or disease depending on a variety of conditions. In the transplant patient population, the need for immunosuppression and widespread use of prophylactic and therapeutic antimicrobial agents create new posttransplant microbiota communities that remain to be fully defined. Studies in mice have demonstrated significant bidirectional interactions between microbiota-derived products and host immune cells. The stimulation of regulatory T cell and T helper cell type 17 cells by specific products leads to maintenance of immune homeostasis versus activation of inflammation, respectively. Dysbiosis may lead to development of antigen cross-reactivity, which may affect alloreactivity. Certain immunologic sequelae of microbiota are pronounced in chronic kidney disease, because of uremia and renal metabolism of microbiota metabolites. Dietary modifications, probiotics, and fecal microbiota transplant have been investigated for alteration of microbiota in humans. Researchers have begun to identify dysbioses associated with clinical conditions, including chronic kidney disease, posttransplant infection, and rejection. This information will allow clinicians not only to select at-risk patients for early intervention, but also to develop therapies that restore the microbiota to a state of homeostasis or tolerance.

Effects of Crude Oil, Dispersant, and Oil-Dispersant Mixtures on Human Fecal Microbiota in an In Vitro Culture System

PubMed Central

Kim, Jong Nam; Kim, Bong-Soo; Kim, Seong-Jae; Cerniglia, Carl E.

2012-01-01

ABSTRACT The Deepwater Horizon oil spill of 2010 raised concerns that dispersant and dispersed oil, as well as crude oil itself, could contaminate shellfish and seafood habitats with hazardous residues that had potential implications for human health and the ecosystem. However, little is known about the effects of crude oil and dispersant on the human fecal microbiota. The aim of this research was to evaluate the potential effects of Deepwater Horizon crude oil, Corexit 9500 dispersant, and their combination on human fecal microbial communities, using an in vitro culture test system. Fecal specimens from healthy adult volunteers were made into suspensions, which were then treated with oil, dispersant, or oil-dispersant mixtures under anaerobic conditions in an in vitro culture test system. Perturbations of the microbial community, compared to untreated control cultures, were assessed using denaturing gradient gel electrophoresis (DGGE), real-time PCR, and pyrosequencing methods. DGGE and pyrosequencing analysis showed that oil-dispersant mixtures reduced the diversity of fecal microbiota from all individuals. Real-time PCR results indicated that the copy numbers of 16S rRNA genes in cultures treated with dispersed oil or oil alone were significantly lower than those in control incubations. The abundance of the Bacteroidetes decreased in crude oil-treated and dispersed-oil-treated cultures, while the Proteobacteria increased in cultures treated with dispersed oil. In conclusion, the human fecal microbiota was affected differently by oil and dispersed oil, and the influence of dispersed oil was significantly greater than that of either oil or dispersant alone compared to control cultures. PMID:23093387

Effect of Oral Capsule– vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection

PubMed Central

Roach, Brandi; Silva, Marisela; Beck, Paul; Rioux, Kevin; Kaplan, Gilaad G.; Chang, Hsiu-Ju; Coward, Stephanie; Goodman, Karen J.; Xu, Huiping; Madsen, Karen; Mason, Andrew; Wong, Gane Ka-Shu; Jovel, Juan; Patterson, Jordan; Louie, Thomas

2017-01-01

Importance Fecal microbiota transplantation (FMT) is effective in preventing recurrent Clostridium difficile infection (RCDI). However, it is not known whether clinical efficacy differs by route of delivery. Objective To determine whether FMT by oral capsule is noninferior to colonoscopy delivery in efficacy. Design, Setting, and Participants Noninferiority, unblinded, randomized trial conducted in 3 academic centers in Alberta, Canada. A total of 116 adult patients with RCDI were enrolled between October 2014 and September 2016, with follow-up to December 2016. The noninferiority margin was 15%. Interventions Participants were randomly assigned to FMT by capsule or by colonoscopy at a 1:1 ratio. Main Outcomes and Measures The primary outcome was the proportion of patients without RCDI 12 weeks after FMT. Secondary outcomes included (1) serious and minor adverse events, (2) changes in quality of life by the 36-Item Short Form Survey on a scale of 0 (worst possible quality of life) to 100 (best quality of life), and (3) patient perception on a scale of 1 (not at all unpleasant) to 10 (extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst). Results Among 116 patients randomized (mean [SD] age, 58 [19] years; 79 women [68%]), 105 (91%) completed the trial, with 57 patients randomized to the capsule group and 59 to the colonoscopy group. In per-protocol analysis, prevention of RCDI after a single treatment was achieved in 96.2% in both the capsule group (51/53) and the colonoscopy group (50/52) (difference, 0%; 1-sided 95% CI, −6.1% to infinity; P < .001), meeting the criterion for noninferiority. One patient in each group died of underlying cardiopulmonary illness unrelated to FMT. Rates of minor adverse events were 5.4% for the capsule group vs 12.5% for the colonoscopy group. There was no significant between-group difference in improvement in quality of life. A significantly greater proportion of participants receiving capsules rated their

Fecal Microbiota in Pediatric Inflammatory Bowel Disease and Its Relation to Inflammation.

PubMed

Kolho, Kaija-Leena; Korpela, Katri; Jaakkola, Tytti; Pichai, Madharasi V A; Zoetendal, Erwin G; Salonen, Anne; de Vos, Willem M

2015-06-01

Inflammatory bowel disease (IBD) is considered to result from interplay between host and intestinal microbiota. While IBD in adults has shown to be associated with marked changes in the intestinal microbiota, there are only a few studies in children, and particularly studies focusing on therapeutic responses are lacking. Hence, this prospective study addressed the intestinal microbiota in pediatric IBD especially related to the level of inflammation. In total, 68 pediatric patients with IBD and 26 controls provided stool and blood samples in a tertiary care hospital and 32 received anti-tumor necrosis factor-α (anti-TNF-α). Blood inflammatory markers and fecal calprotectin levels were determined. The intestinal microbiota was characterized by phylogenetic microarray and qPCR analysis. The microbiota varied along a gradient of increasing intestinal inflammation (indicated by calprotectin levels), which was associated with reduced microbial richness, abundance of butyrate producers, and relative abundance of Gram-positive bacteria (especially Clostridium clusters IV and XIVa). A significant association between microbiota composition and inflammation was indicated by a set of bacterial groups predicting the calprotectin levels (area under curve (AUC) of 0.85). During the induction of anti-TNF-α, the microbial diversity and similarity to the microbiota of controls increased in the responder group by week 6, but not in the non-responders (P<0.01; response related to calprotectin levels). The abundance of six groups of bacteria including those related to Eubacterium rectale and Bifidobacterium spp. predicted the response to anti-TNF-α medication. Intestinal microbiota represents a potential biomarker for correlating the level of inflammation and therapeutic responses to be further validated.

Engineering the gut microbiota to treat hyperammonemia.

PubMed

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

2015-07-01

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

Senior Thai fecal microbiota comparison between vegetarians and non-vegetarians using PCR-DGGE and real-time PCR.

PubMed

Ruengsomwong, Supatjaree; Korenori, Yuki; Sakamoto, Naoshige; Wannissorn, Bhusita; Nakayama, Jiro; Nitisinprasert, Sunee

2014-08-01

The fecal microbiotas were investigated in 13 healthy Thai subjects using polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). Among the 186 DNA bands detected on the polyacrylamide gel, 37 bands were identified as representing 11 species: Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides uniformis, Bacteroides vulgatus, Clostridium colicanis, Eubacterium eligenes, E. rectale, Faecalibacterium prausnitzii, Megamonas funiformis, Prevotella copri, and Roseburia intestinalis, belonging mainly to the groups of Bacteroides, Prevotella, Clostridium, and F. prausnitzii. A dendrogram of the PCR-DGGE divided the subjects; vegetarians and non-vegetarians. The fecal microbiotas were also analyzed using a quantitative real-time PCR focused on Bacteroides, Bifidobacterium, Enterobacteriaceae, Clostrium coccoides-Eubacterium rectale, C. leptum, Lactobacillus, and Prevotella. The nonvegetarian and vegetarian subjects were found to have significant differences in the high abundance of the Bacteroides and Prevotella genera, respectively. No significant differences were found in the counts of Bifidabacterium, Enterobacteriaceae, C. coccoides-E. rectale group, C. leptum group, and Lactobacillus. Therefore, these findings on the microbiota of healthy Thais consuming different diets could provide helpful data for predicting the health of South East Asians with similar diets.

Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics.

PubMed

Yu, Meng; Jia, Hongmei; Zhou, Chao; Yang, Yong; Zhao, Yang; Yang, Maohua; Zou, Zhongmei

2017-05-10

As a prevalent, life-threatening and highly recurrent psychiatric illness, depression is characterized by a wide range of pathological changes; however, its etiology remains incompletely understood. Accumulating evidence supports that gut microbiota affects not only gastrointestinal physiology but also central nervous system (CNS) function and behavior through the microbiota-gut-brain axis. To assess the impact of gut microbiota on fecal metabolic phenotype in depressive conditions, an integrated approach of 16S rRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in chronic variable stress (CVS)-induced depression rat model. Interestingly, depression led to significant gut microbiota changes, at the phylum and genus levels in rats treated with CVS compared to controls. The relative abundances of the bacterial genera Marvinbryantia, Corynebacterium, Psychrobacter, Christensenella, Lactobacillus, Peptostreptococcaceae incertae sedis, Anaerovorax, Clostridiales incertae sedis and Coprococcus were significantly decreased, whereas Candidatus Arthromitus and Oscillibacter were markedly increased in model rats compared with normal controls. Meanwhile, distinct changes in fecal metabolic phenotype of depressive rats were also found, including lower levels of amino acids, and fatty acids, and higher amounts of bile acids, hypoxanthine and stercobilins. Moreover, there were substantial associations of perturbed gut microbiota genera with the altered fecal metabolites, especially compounds involved in the metabolism of tryptophan and bile acids. These results showed that the gut microbiota was altered in association with fecal metabolism in depressive conditions. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be further applied to assess pathogenesis of depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic changes of the respiratory microbiota and its relationship to fecal and blood microbiota in healthy young cats

PubMed Central

Rindt, Hansjorg; Grobman, Megan E.; Graham, Amber; Bishop, Kaitlin; Cohn, Leah A.; Reinero, Carol R.

2017-01-01

Advances in the field of metagenomics using culture-independent methods of microbial identification have allowed characterization of rich and diverse communities of bacteria in the lungs of healthy humans, mice, dogs, sheep and pigs. These data challenge the long held belief that the lungs are sterile and microbial colonization is synonymous with pathology. Studies in humans and animals demonstrate differences in the composition of airway microbiota in health versus disease suggesting respiratory dysbiosis occurs. Using 16S rRNA amplicon sequencing of DNA extracted from rectal and oropharyngeal (OP) swabs, bronchoalveolar lavage fluid (BALF), and blood, our objective was to characterize the fecal, OP, blood, and lower airway microbiota over time in healthy cats. This work in healthy cats, a species in which a respiratory microbiota has not yet been characterized, sets the stage for future studies in feline asthma in which cats serve as a comparative and translational model for humans. Fecal, OP and BALF samples were collected from six healthy research cats at day 0, week 2, and week 10; blood was collected at week 10. DNA was extracted, amplified via PCR, and sequenced using the Illumina MiSeq platform. Representative operational taxonomic units (OTUs) were identified and microbial richness and diversity were assessed. Principal component analysis (PCA) was used to visualize relatedness of samples and PERMANOVA was used to test for significant differences in microbial community composition. Fecal and OP swabs provided abundant DNA yielding a mean±SEM of 65,653±6,145 and 20,6323±4,360 sequences per sample, respectively while BALF and blood samples had lower coverage (1,489±430 and 269±18 sequences per sample, respectively). Oropharyngeal and fecal swabs were significantly richer than BALF (mean number OTUs 93, 88 and 36, respectively; p < 0.001) with no significant difference (p = 0.180) in richness between time points. PCA revealed site-specific microbial

Dynamic changes of the respiratory microbiota and its relationship to fecal and blood microbiota in healthy young cats.

PubMed

Vientós-Plotts, Aida I; Ericsson, Aaron C; Rindt, Hansjorg; Grobman, Megan E; Graham, Amber; Bishop, Kaitlin; Cohn, Leah A; Reinero, Carol R

2017-01-01

Advances in the field of metagenomics using culture-independent methods of microbial identification have allowed characterization of rich and diverse communities of bacteria in the lungs of healthy humans, mice, dogs, sheep and pigs. These data challenge the long held belief that the lungs are sterile and microbial colonization is synonymous with pathology. Studies in humans and animals demonstrate differences in the composition of airway microbiota in health versus disease suggesting respiratory dysbiosis occurs. Using 16S rRNA amplicon sequencing of DNA extracted from rectal and oropharyngeal (OP) swabs, bronchoalveolar lavage fluid (BALF), and blood, our objective was to characterize the fecal, OP, blood, and lower airway microbiota over time in healthy cats. This work in healthy cats, a species in which a respiratory microbiota has not yet been characterized, sets the stage for future studies in feline asthma in which cats serve as a comparative and translational model for humans. Fecal, OP and BALF samples were collected from six healthy research cats at day 0, week 2, and week 10; blood was collected at week 10. DNA was extracted, amplified via PCR, and sequenced using the Illumina MiSeq platform. Representative operational taxonomic units (OTUs) were identified and microbial richness and diversity were assessed. Principal component analysis (PCA) was used to visualize relatedness of samples and PERMANOVA was used to test for significant differences in microbial community composition. Fecal and OP swabs provided abundant DNA yielding a mean±SEM of 65,653±6,145 and 20,6323±4,360 sequences per sample, respectively while BALF and blood samples had lower coverage (1,489±430 and 269±18 sequences per sample, respectively). Oropharyngeal and fecal swabs were significantly richer than BALF (mean number OTUs 93, 88 and 36, respectively; p < 0.001) with no significant difference (p = 0.180) in richness between time points. PCA revealed site-specific microbial

Fecal Microbiota and Metabolome in a Mouse Model of Spontaneous Chronic Colitis: Relevance to Human Inflammatory Bowel Disease.

PubMed

Robinson, Ainsley M; Gondalia, Shakuntla V; Karpe, Avinash V; Eri, Rajaraman; Beale, David J; Morrison, Paul D; Palombo, Enzo A; Nurgali, Kulmira

2016-12-01

Dysbiosis of the gut microbiota may be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms underlying the role of the intestinal microbiome and metabolome in IBD onset and its alteration during active treatment and recovery remain unknown. Animal models of chronic intestinal inflammation with similar microbial and metabolomic profiles would enable investigation of these mechanisms and development of more effective treatments. Recently, the Winnie mouse model of colitis closely representing the clinical symptoms and characteristics of human IBD has been developed. In this study, we have analyzed fecal microbial and metabolomic profiles in Winnie mice and discussed their relevance to human IBD. The 16S rRNA gene was sequenced from fecal DNA of Winnie and C57BL/6 mice to define operational taxonomic units at ≥97% similarity threshold. Metabolomic profiling of the same fecal samples was performed by gas chromatography-mass spectrometry. Composition of the dominant microbiota was disturbed, and prominent differences were evident at all levels of the intestinal microbiome in fecal samples from Winnie mice, similar to observations in patients with IBD. Metabolomic profiling revealed that chronic colitis in Winnie mice upregulated production of metabolites and altered several metabolic pathways, mostly affecting amino acid synthesis and breakdown of monosaccharides to short chain fatty acids. Significant dysbiosis in the Winnie mouse gut replicates many changes observed in patients with IBD. These results provide justification for the suitability of this model to investigate mechanisms underlying the role of intestinal microbiota and metabolome in the pathophysiology of IBD.

Allergy associations with the adult fecal microbiota: Analysis of the American Gut Project

PubMed Central

Hua, Xing; Goedert, James J.; Pu, Angela; Yu, Guoqin; Shi, Jianxin

2015-01-01

Background Alteration of the gut microbial population (dysbiosis) may increase the risk for allergies and other conditions. This study sought to clarify the relationship of dysbiosis with allergies in adults. Methods Publicly available American Gut Project questionnaire and fecal 16S rRNA sequence data were analyzed. Fecal microbiota richness (number of observed species) and composition (UniFrac) were used to compare adults with versus without allergy to foods (peanuts, tree nuts, shellfish, other) and non-foods (drug, bee sting, dander, asthma, seasonal, eczema). Logistic and Poisson regression models adjusted for potential confounders. Odds ratios and 95% confidence intervals (CI) were calculated for lowest vs highest richness tertile. Taxonomy associations considered 122 non-redundant taxa (of 2379 total taxa) with ≥ 0.1% mean abundance. Results Self-reported allergy prevalence among the 1879 participants (mean age, 45.5 years; 46.9% male) was 81.5%, ranging from 2.5% for peanuts to 40.5% for seasonal. Fecal microbiota richness was markedly lower with total allergies (P = 10− 9) and five particular allergies (P ≤ 10− 4). Richness odds ratios were 1.7 (CI 1.3–2.2) with seasonal, 1.8 (CI 1.3–2.5) with drug, and 7.8 (CI 2.3–26.5) with peanut allergy. These allergic participants also had markedly altered microbial community composition (unweighted UniFrac, P = 10− 4 to 10− 7). Total food and non-food allergies were significantly associated with 7 and 9 altered taxa, respectively. The dysbiosis was most marked with nut and seasonal allergies, driven by higher Bacteroidales and reduced Clostridiales taxa. Interpretation American adults with allergies, especially to nuts and seasonal pollen, have low diversity, reduced Clostridiales, and increased Bacteroidales in their gut microbiota. This dysbiosis might be targeted to improve treatment or prevention of allergy. PMID:26870828

Intense Exercise and Aerobic Conditioning Associated with Chromium or L-Carnitine Supplementation Modified the Fecal Microbiota of Fillies

PubMed Central

Feringer, Walter Heinz; Carvalho, Júlia Ribeiro Garcia; Rodrigues, Isadora Mestriner; Jordão, Lilian Rezende; Fonseca, Mayara Gonçalves; Carneiro de Rezende, Adalgiza Souza; de Queiroz Neto, Antonio; Weese, J. Scott; da Costa, Márcio Carvalho

2016-01-01

Recent studies performed in humans and rats have reported that exercise can alter the intestinal microbiota. Athletic horses perform intense exercise regularly, but studies characterizing horse microbiome during aerobic conditioning programs are still limited. Evidence has indicated that this microbial community is involved in the metabolic homeostasis of the host. Research on ergogenic substances using new sequencing technologies have been limited to the intestinal microbiota and there is a considerable demand for scientific studies that verify the effectiveness of these supplements in horses. L-carnitine and chromium are potentially ergogenic substances for athletic humans and horses since they are possibly able to modify the metabolism of carbohydrates and lipids. This study aimed to assess the impact of acute exercise and aerobic conditioning, associated either with L-carnitine or chromium supplementation, on the intestinal microbiota of fillies. Twelve “Mangalarga Marchador” fillies in the incipient fitness stage were distributed into four groups: control (no exercise), exercise, L-carnitine (10g/day) and chelated chromium (10mg/day). In order to investigate the impact of acute exercise or aerobic conditioning on fecal microbiota all fillies undergoing the conditioning program were analyzed as a separate treatment. The fillies underwent two incremental exercise tests before and after training on a treadmill for 42 days at 70–80% of the lactate threshold intensity. Fecal samples were obtained before and 48 h after acute exercise (incremental exercise test). Bacterial populations were characterized by sequencing the V4 region of the 16S rRNA gene using the MiSeq Illumina platform, and 5,224,389 sequences were obtained from 48 samples. The results showed that, overall, the two most abundant phyla were Firmicutes (50.22%) followed by Verrucomicrobia (15.13%). The taxa with the highest relative abundances were unclassified Clostridiales (17.06%) and "5 genus

Intense Exercise and Aerobic Conditioning Associated with Chromium or L-Carnitine Supplementation Modified the Fecal Microbiota of Fillies.

PubMed

Almeida, Maria Luiza Mendes de; Feringer, Walter Heinz; Carvalho, Júlia Ribeiro Garcia; Rodrigues, Isadora Mestriner; Jordão, Lilian Rezende; Fonseca, Mayara Gonçalves; Carneiro de Rezende, Adalgiza Souza; de Queiroz Neto, Antonio; Weese, J Scott; Costa, Márcio Carvalho da; Lemos, Eliana Gertrudes de Macedo; Ferraz, Guilherme de Camargo

2016-01-01

Recent studies performed in humans and rats have reported that exercise can alter the intestinal microbiota. Athletic horses perform intense exercise regularly, but studies characterizing horse microbiome during aerobic conditioning programs are still limited. Evidence has indicated that this microbial community is involved in the metabolic homeostasis of the host. Research on ergogenic substances using new sequencing technologies have been limited to the intestinal microbiota and there is a considerable demand for scientific studies that verify the effectiveness of these supplements in horses. L-carnitine and chromium are potentially ergogenic substances for athletic humans and horses since they are possibly able to modify the metabolism of carbohydrates and lipids. This study aimed to assess the impact of acute exercise and aerobic conditioning, associated either with L-carnitine or chromium supplementation, on the intestinal microbiota of fillies. Twelve "Mangalarga Marchador" fillies in the incipient fitness stage were distributed into four groups: control (no exercise), exercise, L-carnitine (10g/day) and chelated chromium (10mg/day). In order to investigate the impact of acute exercise or aerobic conditioning on fecal microbiota all fillies undergoing the conditioning program were analyzed as a separate treatment. The fillies underwent two incremental exercise tests before and after training on a treadmill for 42 days at 70-80% of the lactate threshold intensity. Fecal samples were obtained before and 48 h after acute exercise (incremental exercise test). Bacterial populations were characterized by sequencing the V4 region of the 16S rRNA gene using the MiSeq Illumina platform, and 5,224,389 sequences were obtained from 48 samples. The results showed that, overall, the two most abundant phyla were Firmicutes (50.22%) followed by Verrucomicrobia (15.13%). The taxa with the highest relative abundances were unclassified Clostridiales (17.06%) and "5 genus

DNA from fecal immunochemical test can replace stool for detection of colonic lesions using a microbiota-based model.

PubMed

Baxter, Nielson T; Koumpouras, Charles C; Rogers, Mary A M; Ruffin, Mack T; Schloss, Patrick D

2016-11-14

There is a significant demand for colorectal cancer (CRC) screening methods that are noninvasive, inexpensive, and capable of accurately detecting early stage tumors. It has been shown that models based on the gut microbiota can complement the fecal occult blood test and fecal immunochemical test (FIT). However, a barrier to microbiota-based screening is the need to collect and store a patient's stool sample. Using stool samples collected from 404 patients, we tested whether the residual buffer containing resuspended feces in FIT cartridges could be used in place of intact stool samples. We found that the bacterial DNA isolated from FIT cartridges largely recapitulated the community structure and membership of patients' stool microbiota and that the abundance of bacteria associated with CRC were conserved. We also found that models for detecting CRC that were generated using bacterial abundances from FIT cartridges were equally predictive as models generated using bacterial abundances from stool. These findings demonstrate the potential for using residual buffer from FIT cartridges in place of stool for microbiota-based screening for CRC. This may reduce the need to collect and process separate stool samples and may facilitate combining FIT and microbiota-based biomarkers into a single test. Additionally, FIT cartridges could constitute a novel data source for studying the role of the microbiome in cancer and other diseases.

Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.

PubMed

Sun, Meng-Fei; Shen, Yan-Qin

2018-04-26

Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed. Copyright © 2018. Published by Elsevier B.V.

Assessment of Fecal Microbiota and Fecal Metabolome in Symptomatic Uncomplicated Diverticular Disease of the Colon.

PubMed

Tursi, Antonio; Mastromarino, Paola; Capobianco, Daniela; Elisei, Walter; Miccheli, Alfredo; Capuani, Giorgio; Tomassini, Alberta; Campagna, Giuseppe; Picchio, Marcello; Giorgetti, GianMarco; Fabiocchi, Federica; Brandimarte, Giovanni

2016-10-01

The aim of this study was to assess fecal microbiota and metabolome in a population with symptomatic uncomplicated diverticular disease (SUDD). Whether intestinal microbiota and metabolic profiling may be altered in patients with SUDD is unknown. Stool samples from 44 consecutive women [15 patients with SUDD, 13 with asymptomatic diverticulosis (AD), and 16 healthy controls (HCs)] were analyzed. Real-time polymerase chain reaction was used to quantify targeted microorganisms. High-resolution proton nuclear magnetic resonance spectroscopy associated with multivariate analysis with partial least-square discriminant analysis (PLS-DA) was applied on the metabolite data set. The overall bacterial quantity did not differ among the 3 groups (P=0.449), with no difference in Bacteroides/Prevotella, Clostridium coccoides, Bifidobacterium, Lactobacillus, and Escherichia coli subgroups. The amount of Akkermansia muciniphila species was significantly different between HC, AD, and SUDD subjects (P=0.017). PLS-DA analysis of nuclear magnetic resonance -based metabolomics associated with microbiological data showed significant discrimination between HCs and AD patients (R=0.733; Q=0.383; P<0.05, LV=2). PLS analysis showed lower N-acetyl compound and isovalerate levels in AD, associated with higher levels of A. municiphila, as compared with the HC group. PLS-DA applied on AD and SUDD samples showed a good discrimination between these 2 groups (R=0.69; Q=0.35; LV=2). SUDD patients were characterized by low levels of valerate, butyrate, and choline and by high levels of N-acetyl derivatives and U1. SUDD and AD do not show colonic bacterial overgrowth, but a significant difference in the levels of fecal A. muciniphila was observed. Moreover, increasing expression of some metabolites as expression of different AD and SUDD metabolic activity was found.

Evaluation of the impact of refrigeration on next generation sequencing-based assessment of the canine and feline fecal microbiota.

PubMed

Weese, J Scott; Jalali, Mohammad

2014-09-30

Evaluation of factors that might impact microbiota assessment is important to avoid spurious results, particularly in field and multicenter studies where sample collection may occur distant from the laboratory. This study evaluated the impact of refrigeration on next generation sequence-based assessment of the canine and feline fecal microbiota. Fecal samples were collected from seven dogs and ten cats, and analysed at baseline and after 3, 7, 10 and 14 days of storage at 4°C. There were no differences in community membership or population structure between timepoints for either dogs or cats, nor were there any differences in richness, diversity and evenness. There were few differences in relative abundance of phyla or predominant genera, with the only differences being significant increases in Actinobacteria between Days 0-14 (P = 0.0184) and 1-14 (P = 0.0182) for canine samples, and a decrease in Erysipelotrichaceae incertae sedis between Day 0 and Day 7 (median 4.9 vs 2.2%, P = 0.046) in feline samples. Storage for at least 14 days at 4°C has limited impact on culture-independent assessment of the canine and feline fecal microbiota, although changes in some individual groups may occur.

Different fecal microbiotas and volatile organic compounds in treated and untreated children with celiac disease.

PubMed

Di Cagno, Raffaella; Rizzello, Carlo G; Gagliardi, Francesca; Ricciuti, Patrizia; Ndagijimana, Maurice; Francavilla, Ruggiero; Guerzoni, M Elisabetta; Crecchio, Carmine; Gobbetti, Marco; De Angelis, Maria

2009-06-01

This study aimed at investigating the fecal microbiotas of children with celiac disease (CD) before (U-CD) and after (T-CD) they were fed a gluten-free diet and of healthy children (HC). Brothers or sisters of T-CD were enrolled as HC. Each group consisted of seven children. PCR-denaturing gradient gel electrophoresis (DGGE) analysis with V3 universal primers revealed a unique profile for each fecal sample. PCR-DGGE analysis with group- or genus-specific 16S rRNA gene primers showed that the Lactobacillus community of U-CD changed significantly, while the diversity of the Lactobacillus community of T-CD was quite comparable to that of HC. Compared to HC, the ratio of cultivable lactic acid bacteria and Bifidobacterium to Bacteroides and enterobacteria was lower in T-CD and even lower in U-CD. The percentages of strains identified as lactobacilli differed as follows: HC (ca. 38%) > T-CD (ca. 17%) > U-CD (ca. 10%). Lactobacillus brevis, Lactobacillus rossiae, and Lactobacillus pentosus were identified only in fecal samples from T-CD and HC. Lactobacillus fermentum, Lactobacillus delbrueckii subsp. bulgaricus, and Lactobacillus gasseri were identified only in several fecal samples from HC. Compared to HC, the composition of Bifidobacterium species of T-CD varied, and it varied even more for U-CD. Forty-seven volatile organic compounds (VOCs) belonging to different chemical classes were identified using gas-chromatography mass spectrometry-solid-phase microextraction analysis. The median concentrations varied markedly for HC, T-CD, and U-CD. Overall, the r(2) values for VOC data for brothers and sisters were equal to or lower than those for unrelated HC and T-CD. This study shows the effect of CD pathology on the fecal microbiotas of children.

Red wine consumption is associated with fecal microbiota and malondialdehyde in a human population.

PubMed

Cuervo, Adriana; Reyes-Gavilán, Clara G de Los; Ruas-Madiedo, Patricia; Lopez, Patricia; Suarez, Ana; Gueimonde, Miguel; González, Sonia

2015-01-01

Red wine intake has been associated with a lower risk of cardiovascular disease; its polyphenol content is the primary cause of antioxidant and anti-inflammatory properties attributed to this beverage. However, the way in which these activities are exerted is not yet clear, although some authors have proposed that intestinal microbiota could be implicated. The association between red wine intake, inflammation, and oxidative stress parameters and fecal microbial populations has been explored in 38 adult volunteers. Food intake was recorded by means of an annual food frequency questionnaire (FFQ). Energy, cholesterol, and ethanol intake were analyzed using the nutrient Food Composition Tables developed by Centro de Enseñanza Superior de Nutrición y Dietética (CESNID) and polyphenol intake was obtained from the Phenol-Explorer Database. Fecal levels of Akkermansia, Bacteroides, Bifidobacterium, Blautia coccoides group, Clostridium leptum group, Lactobacillus group, and Faecalibacterium prausnitzii were determined by quantitative polymerase chain reaction. Serum concentrations of C-reactive protein (CRP), malondialdehyde (MDA), total antioxidant capacity (TAC), cholesterol, triglycerides and glucose were analyzed by standard methods. Subjects with regular consumption of red wine (mean = 100 ml/day) had lower serum concentrations of MDA and lower fecal levels of B. coccoides, C. leptum, Bifidobacterium, and Lactobacillus. A positive association between MDA levels and B. coccoides and Lactobacillus was also found. Regular consumption of red wine appears to be associated with a reduced serum lipoperoxidation in which the intestinal microbiota may be involved.

The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs

PubMed Central

Jeffery, Nick D.; Barker, Andrew K.; Alcott, Cody J.; Levine, Jon M.; Meren, Ilyssa; Wengert, Jane; Jergens, Albert E.; Suchodolski, Jan S.

2017-01-01

Meningoencephalomyelitis of unknown origin (MUO) is a common, naturally-occurring, clinical disease of pet dogs. It is an immune-mediated condition that has many similarities with experimental autoimmune encephalitis (EAE) in rodents and so investigation of its pathogenesis may aid in understanding factors that contribute to development of multiple sclerosis in people. Gut microbiota are known to modulate immune responses that influence susceptibility to immune-mediated brain disease. In this study we aimed to compare abundance of specific constituents of the fecal microbiota, namely Faecalibacterium prausnitzii and Prevotellaceae, between dogs diagnosed with MUO and matched controls. Fecal samples were obtained from 20 dogs diagnosed with MUO and 20 control dogs matched for breed, age and gender. Bacterial abundance was measured using qPCR and 16S rRNA sequencing. We found that Prevotellaceae were significantly less abundant in cases compared with controls (p = 0.003) but there was no difference in abundance of F.prausnitzii. There was no evidence of other differences in gut microbiota between groups. These data, derived from this naturally-occurring canine clinical model, provide strong corroborative evidence that high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease. PMID:28125651

The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs.

PubMed

Jeffery, Nick D; Barker, Andrew K; Alcott, Cody J; Levine, Jon M; Meren, Ilyssa; Wengert, Jane; Jergens, Albert E; Suchodolski, Jan S

2017-01-01

Meningoencephalomyelitis of unknown origin (MUO) is a common, naturally-occurring, clinical disease of pet dogs. It is an immune-mediated condition that has many similarities with experimental autoimmune encephalitis (EAE) in rodents and so investigation of its pathogenesis may aid in understanding factors that contribute to development of multiple sclerosis in people. Gut microbiota are known to modulate immune responses that influence susceptibility to immune-mediated brain disease. In this study we aimed to compare abundance of specific constituents of the fecal microbiota, namely Faecalibacterium prausnitzii and Prevotellaceae, between dogs diagnosed with MUO and matched controls. Fecal samples were obtained from 20 dogs diagnosed with MUO and 20 control dogs matched for breed, age and gender. Bacterial abundance was measured using qPCR and 16S rRNA sequencing. We found that Prevotellaceae were significantly less abundant in cases compared with controls (p = 0.003) but there was no difference in abundance of F.prausnitzii. There was no evidence of other differences in gut microbiota between groups. These data, derived from this naturally-occurring canine clinical model, provide strong corroborative evidence that high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease.

Effects of preservation method on canine (Canis lupus familiaris) fecal microbiota.

PubMed

Horng, Katti R; Ganz, Holly H; Eisen, Jonathan A; Marks, Stanley L

2018-01-01

Studies involving gut microbiome analysis play an increasing role in the evaluation of health and disease in humans and animals alike. Fecal sampling methods for DNA preservation in laboratory, clinical, and field settings can greatly influence inferences of microbial composition and diversity, but are often inconsistent and under-investigated between studies. Many laboratories have utilized either temperature control or preservation buffers for optimization of DNA preservation, but few studies have evaluated the effects of combining both methods to preserve fecal microbiota. To determine the optimal method for fecal DNA preservation, we collected fecal samples from one canine donor and stored aliquots in RNAlater, 70% ethanol, 50:50 glycerol:PBS, or without buffer at 25 °C, 4 °C, and -80 °C. Fecal DNA was extracted, quantified, and 16S rRNA gene analysis performed on Days 0, 7, 14, and 56 to evaluate changes in DNA concentration, purity, and bacterial diversity and composition over time. We detected overall effects on bacterial community of storage buffer ( F -value = 6.87, DF  = 3, P  < 0.001), storage temperature ( F -value=1.77, DF  = 3, P  = 0.037), and duration of sample storage ( F -value = 3.68, DF  = 3, P  < 0.001). Changes in bacterial composition were observed in samples stored in -80 °C without buffer, a commonly used method for fecal DNA storage, suggesting that simply freezing samples may be suboptimal for bacterial analysis. Fecal preservation with 70% ethanol and RNAlater closely resembled that of fresh samples, though RNAlater yielded significantly lower DNA concentrations ( DF  = 8.57, P  < 0.001). Although bacterial composition varied with temperature and buffer storage, 70% ethanol was the best method for preserving bacterial DNA in canine feces, yielding the highest DNA concentration and minimal changes in bacterial diversity and composition. The differences observed between samples highlight the need to consider

Characterization of egg laying hen and broiler fecal microbiota in poultry farms in Croatia, Czech Republic, Hungary and Slovenia.

PubMed

Videnska, Petra; Rahman, Md Masudur; Faldynova, Marcela; Babak, Vladimir; Matulova, Marta Elsheimer; Prukner-Radovcic, Estella; Krizek, Ivan; Smole-Mozina, Sonja; Kovac, Jasna; Szmolka, Ama; Nagy, Bela; Sedlar, Karel; Cejkova, Darina; Rychlik, Ivan

2014-01-01

Poultry meat is the most common protein source of animal origin for humans. However, intensive breeding of animals in confined spaces has led to poultry colonisation by microbiota with a zoonotic potential or encoding antibiotic resistances. In this study we were therefore interested in the prevalence of selected antibiotic resistance genes and microbiota composition in feces of egg laying hens and broilers originating from 4 different Central European countries determined by real-time PCR and 16S rRNA gene pyrosequencing, respectively. strA gene was present in 1 out of 10,000 bacteria. The prevalence of sul1, sul2 and tet(B) in poultry microbiota was approx. 6 times lower than that of the strA gene. tet(A) and cat were the least prevalent being present in around 3 out of 10,000,000 bacteria forming fecal microbiome. The core chicken fecal microbiota was formed by 26 different families. Rather unexpectedly, representatives of Desulfovibrionaceae and Campylobacteraceae, both capable of hydrogen utilisation in complex microbial communities, belonged among core microbiota families. Understanding the roles of individual population members in the total metabolism of the complex community may allow for interventions which might result in the replacement of Campylobacteraceae with Desulfovibrionaceae and a reduction of Campylobacter colonisation in broilers, carcasses, and consequently poultry meat products.

Characterization of Egg Laying Hen and Broiler Fecal Microbiota in Poultry Farms in Croatia, Czech Republic, Hungary and Slovenia

PubMed Central

Videnska, Petra; Rahman, Md. Masudur; Faldynova, Marcela; Babak, Vladimir; Matulova, Marta Elsheimer; Prukner-Radovcic, Estella; Krizek, Ivan; Smole-Mozina, Sonja; Kovac, Jasna; Szmolka, Ama; Nagy, Bela; Sedlar, Karel; Cejkova, Darina; Rychlik, Ivan

2014-01-01

Poultry meat is the most common protein source of animal origin for humans. However, intensive breeding of animals in confined spaces has led to poultry colonisation by microbiota with a zoonotic potential or encoding antibiotic resistances. In this study we were therefore interested in the prevalence of selected antibiotic resistance genes and microbiota composition in feces of egg laying hens and broilers originating from 4 different Central European countries determined by real-time PCR and 16S rRNA gene pyrosequencing, respectively. strA gene was present in 1 out of 10,000 bacteria. The prevalence of sul1, sul2 and tet(B) in poultry microbiota was approx. 6 times lower than that of the strA gene. tet(A) and cat were the least prevalent being present in around 3 out of 10,000,000 bacteria forming fecal microbiome. The core chicken fecal microbiota was formed by 26 different families. Rather unexpectedly, representatives of Desulfovibrionaceae and Campylobacteraceae, both capable of hydrogen utilisation in complex microbial communities, belonged among core microbiota families. Understanding the roles of individual population members in the total metabolism of the complex community may allow for interventions which might result in the replacement of Campylobacteraceae with Desulfovibrionaceae and a reduction of Campylobacter colonisation in broilers, carcasses, and consequently poultry meat products. PMID:25329397

Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases.

PubMed

Konturek, P C; Haziri, D; Brzozowski, T; Hess, T; Heyman, S; Kwiecien, S; Konturek, S J; Koziel, J

2015-08-01

In the recent decade our understanding of the role of the human gut microbiome has been revolutionized by advances in development of molecular methods. Approximately, up to 100 trillion (10(14)) microorganisms per human body colonize the intestinal tract making an additional acquired organ that provides many vital functions to the host. A healthy gut microbiome can be defined by the presence of the various classes of microbes that enhance metabolism, resistance to infection and inflammation, prevention against cancer and autoimmunity and that positively influence so called braingut axis. Diet represents one of the most important driving forces that besides environmental and genetic factors, can define and influence the microbial composition of the gut. Aging process due to different changes in gut physiology (i.e. gastric hypochlorhydria, motility disorders, use of drugs, degenerative changes in enteric nervous system) has a profound effect on the composition, diversity and functional features of gut microbiota. A perturbed aged gut microbiome has been associated with the increasing number of gastrointestinal (e.g. Clostridium difficile infection - CDI) and non-gastrointestinal diseases (metabolic syndrome, diabetes mellitus, fatty liver disease, atherosclerosis etc.). Fecal microbiota transplantation (FMT) is a highly effective method in the treatment of refractory CDI. FMT is the term used when stool is taken from a healthy individual and instilled during endoscopy (colonoscopy or enteroscopy) into a gut of the sick person to cure certain disease. FMT represents an effective therapy in patient with recurrent CDI and the effectiveness of FMT in the prevention of CDI recurrence had reached approx. 90%. There is also an increasing evidence that the manipulation of gut microbiota by FMT represents a promising therapeutic method in patients with inflammatory bowel disease and irritable bowel syndrome. There is also an increased interest in the role of FMT for the

Antibiotic and Modulation of Microbiota: A New Paradigm?

PubMed

Rizzatti, Gianenrico; Ianiro, Gianluca; Gasbarrini, Antonio

2018-06-16

Recently new insights on gut microbiota have revolutionized many concepts of the modern medicine. The alteration of microbiota, which is called dysbiosis, has been associated with an expanding list of diseases and conditions. The development of next-generation sequencing techniques allowed comprehensive analysis of gut microbiota composition without the limitations of classic culture methods. Furthermore, introduction of functional techniques such as metabolomics and proteomics allowed for integrated analysis thus obtaining more robust insights on microbiota functions in health and disease. These tools allow to address the role of factors able to modify the gut microbiota, the so called "microbiota influencers." These data are useful to explain the physiopathology of several disease and thus to identify new potential therapeutic targets. Among microbiota influencers, many studies focused on the impact of antibiotic administration on the gut microbiota, because of their widespread use. Notably, beside the known beneficial effect of antibiotic in treating infectious diseases, these drugs have shown detrimental effects on gut microbiota which, in turn, might have long-term consequences on the host. Finally, therapeutic modulation of gut microbiota, by means of selected antibiotics with eubiotic effects, probiotics and with fecal microbiota transplantation seems of great interest as it might be able to prevent or even revert antibiotic-induced dysbiosis.

Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.

PubMed

Spychala, Monica S; Venna, Venugopal Reddy; Jandzinski, Michal; Doran, Sarah J; Durgan, David J; Ganesh, Bhanu Priya; Ajami, Nadim J; Putluri, Nagireddy; Graf, Joerg; Bryan, Robert M; McCullough, Louise D

2018-05-07

Objective Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation. Methods Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke. Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke. Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG). Mice were subjected to ischemic stroke (MCAO) or sham surgery. During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S rRNA analysis of bacterial content. Results We found that the microbiota is altered after experimental stroke in young mice, and resembles the biome of uninjured aged mice. In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased ∼9-fold (P<0.001) compared to young. This increased F:B ratio in aged mice is indicative of dysbiosis. Altering the microbiota in young by fecal gavage to resemble that of aged mice (∼6-fold increase in F:B ratio, P<0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels. Conversely, altering the microbiota in aged to resemble that of young (∼9-fold decrease in F:B ratio, P<0.001) increased survival and improved recovery following MCAO. Interpretation Aged biome increased the levels of systemic pro-inflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age-related diseases. This article is protected by copyright. All rights reserved. © 2018 American Neurological Association.

Impact of gut colonization with butyrate producing microbiota on respiratory viral infection following allo-HCT.

PubMed

Haak, Bastiaan W; Littmann, Eric R; Chaubard, Jean-Luc; Pickard, Amanda J; Fontana, Emily; Adhi, Fatima; Gyaltshen, Yangtsho; Ling, Lilan; Morjaria, Sejal M; Peled, Jonathan U; van den Brink, Marcel R; Geyer, Alexander I; Cross, Justin R; Pamer, Eric G; Taur, Ying

2018-04-19

Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT), and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HSCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S rRNA sequencing to determine microbiota composition and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate producing bacteria were a five-fold less likely to develop viral LRTI, independent of other factors (adjusted HR=0.22, 95% CI 0.04 - 0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients. Copyright © 2018 American Society of Hematology.

Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation.

PubMed

Weber, Daniela; Jenq, Robert R; Peled, Jonathan U; Taur, Ying; Hiergeist, Andreas; Koestler, Josef; Dettmer, Katja; Weber, Markus; Wolff, Daniel; Hahn, Joachim; Pamer, Eric G; Herr, Wolfgang; Gessner, André; Oefner, Peter J; van den Brink, Marcel R M; Holler, Ernst

2017-05-01

In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. This retrospective analysis of 621 patients who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York assessed the impact of timing of peritransplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (P < .001) and a decrease in fecal abundance of commensal Clostridiales (P = .03) compared with late antibiotic treatment, which was particularly significant (P = .005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment before ASCT was further associated with a higher TRM (34%, 79/236) compared with post-ASCT (21%, 62/297, P = .001) or no antibiotics (7%, 6/88, P < .001). Timing of antibiotic treatment was the dominant independent risk factor for TRM (HR, 2.0; P ≤ .001) in multivariate analysis besides increase age (HR, 2.15; P = .004), reduced Karnofsky performance status (HR, 1.47; P = .03), and female donor-male recipient sex combination (HR, 1.56; P = .02) A competing risk analysis revealed the independent effect of early initiation of antibiotics on graft-versus-host disease-related TRM (P = .004) in contrast to infection-related TRM and relapse (not significant). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales, calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment. Copyright © 2017 The American Society for Blood and Marrow Transplantation

Microbiota disruption induced by early use of broad spectrum antibiotics is an independent risk factor of outcome after allogeneic stem cell transplantation

PubMed Central

Weber, Daniela; Jenq, Robert R.; Peled, Jonathan U.; Taur, Ying; Hiergeist, Andreas; Koestler, Josef; Dettmer, Katja; Weber, Markus; Wolff, Daniel; Hahn, Joachim; Pamer, Eric G.; Herr, Wolfgang; Gessner, André; Oefner, Peter J.; van den Brink, Marcel R.M.; Holler, Ernst

2017-01-01

In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. Here, in a retrospective analysis of 621 patients, who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York, we assessed the impact of timing of peri-transplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (p<0.001) and a decrease in fecal abundance of commensal Clostridiales (p=0.03) compared to late antibiotic treatment, which was particularly significant (p=0.005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment prior to ASCT was further associated with a higher TRM (34%, n=79/236) compared to post-ASCT (21% n=62/297, p=0.001) or no antibiotics (7% n=6/88, p<0.001). Timing of antibiotic treatment was the dominant independent risk factor for TRM (HR 2.0, p≤0.001) in multivariate analysis beside increase age (HR 2.15, p=0.004), reduced Karnofsky performance status (HR 1.47, p=0.03) and female donor/ male recipient sex combination (HR 1.56, p=0.02) A competing-risk analysis revealed the independent effect of early initiation of antibiotics on GvHD-related TRM (p=0.004) in contrast to infection-related TRM and relapse (p=ns). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment. PMID:28232086

Prevention and treatment of Clostridium difficile associated diarrhea by reconstitution of the microbiota.

PubMed

Eliakim-Raz, Noa; Bishara, Jihad

2018-05-21

This review summarizes the latest advances in treating and preventing Clostridium difficile infection (CDI), the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. As customary antibiotic therapies against C. difficile, metronidazole and vancomycin, are broad spectrum, they affect greatly the gut microbiota, which result in very high recurrence rates. Therefore, new strategies are researched intensively. New therapies focus on limiting further destruction of the gut microbiota or restoring the microbiota to its pre-destructed state. These include new antibiotics, such as fidaxomicin, which demonstrates reduced CDI recurrences, among other new drugs, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally, monoclonal antibodies against C. difficile toxins which offer protection against recurrences.

Gut Microbial Community Structure and Complications Following Kidney Transplantation: A Pilot Study

PubMed Central

Lee, John R.; Muthukumar, Thangamani; Dadhania, Darshana; Toussaint, Nora C.; Ling, Lilan; Pamer, Eric; Suthanthiran, Manikkam

2014-01-01

Background The gut microbiome plays a role in the regulation of the immune system. Methods We prospectively enrolled 26 kidney transplant recipients and collected serial fecal specimens (N=85) during the first three months of transplantation. We characterized bacterial composition by PCR amplification of the 16S rRNA V4-V5 variable region and deep sequencing using the Illumina® MiSeq platform. Results An increase in the relative abundance of Proteobacteria was observed in the post-transplantation specimens compared to pre-transplantation specimens (P=0.04, Wilcoxon signed-rank test). In patients with post-transplant diarrhea, the mean(±SD) Shannon diversity index was lower in those with diarrhea (N=6) than those without diarrhea (N=9) (2.5±0.3 vs. 3.4±0.8, P=0.02, Wilcoxon rank-sum test). Principal coordinate analysis (PCoA) showed clear separation between the two groups, and linear discriminant analysis effect size (LEfSe) method revealed that Bacteroides, Ruminococcus, Coprococcus, and Dorea were significantly lower in the patients with diarrhea. PCoA analysis also showed clear separation between the acute rejection (AR) group (N=3) and the no AR group (N=23) and LEfSe method revealed several significant differences between the two groups. Fecal abundance of Enterococcus was associated with Enterococcus urinary tract infection (UTI). The median Enterococcus fecal abundance was 24% (Range: 8% to 95%) in the 3 patients with Enterococcus UTI compared to 0% in the 23 patients without Enterococcus UTI (Interquartile range: 0.00% to 0.08%)(P=0.005, Wilcoxon rank-sum test). Conclusions Our pilot study identified significant alterations in the gut microbiota following kidney transplantation. Moreover, distinct microbiota structures were observed in allograft recipients with post-transplant diarrhea, AR, and Enterococcus UTI. PMID:25289916

Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress.

PubMed

Zaborin, Alexander; Krezalek, Monika; Hyoju, Sanjiv; Defazio, Jennifer R; Setia, Namrata; Belogortseva, Natalia; Bindokas, Vytautas P; Guo, Qiti; Zaborina, Olga; Alverdy, John C

2017-02-01

Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts' microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery. This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts. Copyright © 2017 the American Physiological Society.

Comparison Between the Fecal Bacterial Microbiota of Healthy and Diarrheic Captive Musk Deer

PubMed Central

Li, Yimeng; Hu, Xiaolong; Yang, Shuang; Zhou, Juntong; Qi, Lei; Sun, Xiaoning; Fan, Mengyuan; Xu, Shanghua; Cha, Muha; Zhang, Meishan; Lin, Shaobi; Liu, Shuqiang; Hu, Defu

2018-01-01

Diarrhea constitutes one of the most common diseases affecting the survival of captive musk deer and is usually caused by an imbalance in intestinal microbiota. Currently, research regarding the structure and function of intestinal microbiota in diarrheic musk deer is lacking. Therefore, in the present study, high-throughput 16S-rRNA gene sequencing was used to analyze the intestinal microbiota in feces of healthy captive musk deer (HMD) (n = 8) and musk deer with mild (MMD) (n = 8), and severe (n = 5) (SMD) diarrhea to compare the difference in intestinal microbiota of musk deer under various physiological conditions. The results showed that the diversity of HMD fecal microbiota was significantly higher than that of the two diarrhea samples. β Diversity results indicated that there were extremely significant differences in bacterial communities between the HMD sample and the MMD and SMD samples. However, no significant difference was found between the two diarrhea samples. LefSe analysis showed that the degree of intestinal physiological dysfunction in musk deer was correlated with the types of major pathogens. The main pathogen in the MMD group is Escherichia–Shigella, whereas Fusobacterium is the main pathogen in the SMD group. PICRUSt functional profile prediction indicated that the intestinal microbiota disorder could also lead to changes in the abundance of genes in metabolic pathways of the immune system. Altogether, this study provides a theoretical basis for the exploration of treatments for diarrhea in captive musk deer, which is of considerable significance to the implementation of the musk deer release into the wild program. PMID:29551996

Reemergence of Lower-Airway Microbiota in Lung Transplant Patients with Cystic Fibrosis.

PubMed

Syed, Saad A; Whelan, Fiona J; Waddell, Barbara; Rabin, Harvey R; Parkins, Michael D; Surette, Michael G

2016-12-01

Chronic lung infections are a hallmark of cystic fibrosis; they are responsible for progressive airway destruction and ultimately lead to respiratory death or the requirement for life-saving bilateral lung transplant. Furthermore, recurrent isolation of airway pathogens such as Pseudomonas aeruginosa in the allograft after transplant is associated with adverse outcomes, including bronchiolitis obliterans syndrome and acute infections. Little information exists on the impact of bilateral lung transplant on the lower-airway microbiota. To compare, at a microbiome and single-pathogen level (P. aeruginosa), the bacterial communities in pre- and post-transplant samples. We retrospectively accessed our biobank of sputum samples and sputum-derived bacterial pathogens for patients who had matched samples, including those who were clinically stable before transplant, those who had a pulmonary exacerbation before transplant, and those who had pulmonary exacerbation after transplant. We used 16S ribosomal RNA gene sequencing to characterize the lower-airway microbiome of 14 adult transplant patients with cystic fibrosis. Genotyping and phenotyping of P. aeruginosa isolates from 12 of these patients with matched isolates was performed. Although α-diversity (richness and evenness) of patient microbiomes was similar before and after transplant, β- diversity (core microbiome composition) measures stratified patients evenly into two groups with more similar and more dissimilar communities. P. aeruginosa strains isolated before transplant were found to reemerge in 11 of 12 patients; however, phenotypic variation was observed. These findings indicate that recolonization by P. aeruginosa after transplant is almost always strain specific, suggesting a within-host source. The polymicrobial colonization of the airways after transplant does not always reflect the pretransplant sputum microbiota.

Diet and Gut Microbiota in Health and Disease.

PubMed

Shen, Ting-Chin David

2017-01-01

Gut microbiota plays an important role in host health maintenance and disease pathogenesis. The development of a stable and diverse gut microbiota is essential to various host physiologic functions such as immunoregulation, pathogen prevention, energy harvest, and metabolism. At the same time, a dysbiotic gut microbiota associated with disease is altered in structure and function, and often characterized by a decrease in species richness and proliferation of pathogenic bacterial taxa. As a shared substrate between the host and the gut microbiota, diet significantly impacts the health and disease states of the host both directly and through gut microbial metabolite production. This is demonstrated in the examples of short-chain fatty acid and trimethylamine production via bacterial metabolism of dietary complex carbohydrates and choline, respectively. In disorders related to mucosal immune dysregulation such as inflammatory bowel disease, the dysbiotic gut microbiota and diet contribute to its pathogenesis. Reversal of dysbiosis through fecal microbiota transplantation and dietary interventions may thus represent important strategies to modify the gut microbiota and its metabolite production for health maintenance as well as disease prevention and management. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer.

PubMed

van Beurden, Yvette H; van Gils, Tom; van Gils, Nienke A; Kassam, Zain; Mulder, Chris J J; Aparicio-Pagés, Nieves

2016-09-01

Treatment of refractory celiac disease type II (RCD II) and preventing the development of an enteropathy associated T-cell lymphoma in these patients is still difficult. In this case report, we describe a patient with RCD II who received fecal microbiota transfer as treatment for a recurrent Clostridium difficile infection, and remarkably showed a full recovery of duodenal villi and disappearance of celiac symptoms. This case suggests that altering the gut microbiota may hold promise in improving the clinical and histological consequences of celiac disease and/or RCD II.

Detection of cytomegalovirus DNA in fecal samples as a method for CMV enterocolitis diagnosis after allogeneic stem cell transplantation.

PubMed

Zavrelova, Alzbeta; Radocha, Jakub; Pliskova, Lenka; Paterova, Pavla; Vejrazkova, Eva; Cyrany, Jiri; Gabalec, Filip; Podhola, Miroslav; Zak, Pavel

2018-05-16

Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.

[Current view on gut microbiota].

PubMed

Bourlioux, P

2014-01-01

Gut microbiota is more and more important since metagenomic research have brought new knowledge on this topic especially for human health. Firstly, gut microbiota is a key element for our organism he lives in symbiosis with. Secondly, it interacts favorably with many physiological functions of our organism. Thirdly, at the opposite, it can be an active participant in intestinal pathologies linked to a dysbiosis mainly in chronic inflammatory bowel diseases like Crohn disease or ulcerative colitis but also in obesity, metabolic syndrome, and more prudently in autism and behavioral disorders. In order to keep a good health, it is essential to protect our gut microbiota as soon as our young age and maintain it healthy. Face to a more and more important number of publications for treating certain digestive diseases with fecal microbial transplantation, it needs to be very careful and recommend further studies in order to assess risks and define standardized protocols. Gut microbiota metabolic capacities towards xenobiotics need to be developed, and we must take an interest in the modifications they induce on medicinal molecules. On the other hand, it is essential to study the potent effects of pesticides and other pollutants on microbiota functions. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Recommendations for the use of faecal microbiota transplantation "stool transplantation": consensus of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) in cooperation with the Austrian Society of Infectious Diseases and Tropical Medicine].

PubMed

Kump, P K; Krause, R; Steininger, C; Gröchenig, H P; Moschen, A; Madl, C; Novacek, G; Allerberger, F; Högenauer, C

2014-12-01

The intestinal microbiota has a pivotal role in the maintenance of health of the human organism, especially in the defense against pathogenic microorganisms. Alterations in the microbiota, also termed dysbiosis, seem to be involved in the pathogenesis of a variety of intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT), also known as stool transplantation, is a therapeutic procedure aiming at restoring an altered intestinal microbiota by administration of stool microorganisms from a healthy donor into the intestinal tract of a patient. FMT is most commonly used for recurrent forms of Clostridium difficile infections (CDI). There are currently many cohort studies in a large number of patients and a randomized controlled trial showing a dramatic effect of FMT for this indication. Therefore FMT is recommended by international medical societies for the treatment of recurrent CDI with high scientific evidence. Other potential indications are the treatment of fulminant CDI or the treatment of inflammatory bowel diseases. In the practical utilization of FMT there are currently several open questions regarding the screening of stool donors, the processing of stool and the mode of FMT application. Different modes of FMT application have been described, the application into the colon has to be preferred due to less reported side effects than the application into the upper gastrointestinal tract. So far only very few side effects due to FMT have been reported, nevertheless the use and risks of FMT are currently intensely debated in the medical community. This consensus report of the Austrian society of gastroenterology and hepatology (ÖGGH) in cooperation with the Austrian society of infectious diseases and tropical medicine provides instructions for physicians who want to use FMT which are based on the current medical literature. © Georg Thieme Verlag KG Stuttgart · New York.

Dysbiosis of the Fecal Microbiota in Cattle Infected with Mycobacterium avium subsp. paratuberculosis

PubMed Central

Vecchiarelli, Bonnie; Indugu, Nagaraju; Kumar, Sanjay; Gallagher, Susan C.; Fyock, Terry L.; Sweeney, Raymond W.

2016-01-01

Johne's disease (JD) is a chronic, intestinal infection of cattle, caused by Mycobacterium avium subsp. paratuberculosis (MAP). It results in granulomatous inflammation of the intestinal lining, leading to malabsorption, diarrhea, and weight loss. Crohn’s disease (CD), a chronic, inflammatory gastrointestinal disease of humans, has many clinical and pathologic similarities to JD. Dysbiosis of the enteric microbiota has been demonstrated in CD patients. It is speculated that this dysbiosis may contribute to the intestinal inflammation observed in those patients. The purpose of this study was to investigate the diversity patterns of fecal bacterial populations in cattle infected with MAP, compared to those of uninfected control cattle, using phylogenomic analysis. Fecal samples were selected to include samples from 20 MAP-positive cows; 25 MAP-negative herdmates; and 25 MAP-negative cows from a MAP-free herd. The genomic DNA was extracted; PCR amplified sequenced on a 454 Roche platform, and analyzed using QIIME. Approximately 199,077 reads were analyzed from 70 bacterial communities (average of 2,843 reads/sample). The composition of bacterial communities differed between the 3 treatment groups (P < 0.001; Permanova test). Taxonomic assignment of the operational taxonomic units (OTUs) identified 17 bacterial phyla across all samples. Bacteroidetes and Firmicutes constituted more than 95% of the bacterial population in the negative and exposed groups. In the positive group, lineages of Actinobacteria and Proteobacteria increased and those of Bacteroidetes and Firmicutes decreased (P < 0.001). Actinobacteria was highly abundant (30% of the total bacteria) in the positive group compared to exposed and negative groups (0.1–0.2%). Notably, the genus Arthrobacter was found to predominate Actinobacteria in the positive group. This study indicates that MAP-infected cattle have a different composition of their fecal microbiota than MAP-negative cattle. PMID:27494144

Dysbiosis of the Fecal Microbiota in Cattle Infected with Mycobacterium avium subsp. paratuberculosis.

PubMed

Fecteau, Marie-Eve; Pitta, Dipti W; Vecchiarelli, Bonnie; Indugu, Nagaraju; Kumar, Sanjay; Gallagher, Susan C; Fyock, Terry L; Sweeney, Raymond W

2016-01-01

Johne's disease (JD) is a chronic, intestinal infection of cattle, caused by Mycobacterium avium subsp. paratuberculosis (MAP). It results in granulomatous inflammation of the intestinal lining, leading to malabsorption, diarrhea, and weight loss. Crohn's disease (CD), a chronic, inflammatory gastrointestinal disease of humans, has many clinical and pathologic similarities to JD. Dysbiosis of the enteric microbiota has been demonstrated in CD patients. It is speculated that this dysbiosis may contribute to the intestinal inflammation observed in those patients. The purpose of this study was to investigate the diversity patterns of fecal bacterial populations in cattle infected with MAP, compared to those of uninfected control cattle, using phylogenomic analysis. Fecal samples were selected to include samples from 20 MAP-positive cows; 25 MAP-negative herdmates; and 25 MAP-negative cows from a MAP-free herd. The genomic DNA was extracted; PCR amplified sequenced on a 454 Roche platform, and analyzed using QIIME. Approximately 199,077 reads were analyzed from 70 bacterial communities (average of 2,843 reads/sample). The composition of bacterial communities differed between the 3 treatment groups (P < 0.001; Permanova test). Taxonomic assignment of the operational taxonomic units (OTUs) identified 17 bacterial phyla across all samples. Bacteroidetes and Firmicutes constituted more than 95% of the bacterial population in the negative and exposed groups. In the positive group, lineages of Actinobacteria and Proteobacteria increased and those of Bacteroidetes and Firmicutes decreased (P < 0.001). Actinobacteria was highly abundant (30% of the total bacteria) in the positive group compared to exposed and negative groups (0.1-0.2%). Notably, the genus Arthrobacter was found to predominate Actinobacteria in the positive group. This study indicates that MAP-infected cattle have a different composition of their fecal microbiota than MAP-negative cattle.

Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.

PubMed

Beaume, M; Köhler, T; Greub, G; Manuel, O; Aubert, J-D; Baerlocher, L; Farinelli, L; Buckling, A; van Delden, C

2017-01-17

In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft.

The gut microbiota and the liver: implications for clinical practice.

PubMed

Quigley, Eamonn M; Monsour, Howard P

2013-11-01

While a central role for the microbiota in the precipitation of infectious and non-infectious complications of liver disease has been long established, evidence for a more fundamental role in the etiology of several liver diseases continues to accumulate. However, though progress is rapidly occurring in this area, the definitive delineation of the precise relevance of changes in the microbiota to various forms and stages of liver disease is still far from complete. While high quality clinical evidence supports the use of antibiotic therapy, in the management of hepatic encephalopathy, spontaneous bacterial peritonitis and other infectious complications, how these interventions impact on the microbiota and microbiota-host interactions has not been clearly defined. Although probiotics and even, perhaps, fecal transplantation hold promise in the management of liver disease, and the potential impact of probiotics is supported by a considerable amount of laboratory data, high-quality clinical evidence is scanty.

Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective.

PubMed

Han, Jun-Ling; Lin, Hui-Ling

2014-12-21

The incidence of type 2 diabetes (T2DM) is rapidly increasing worldwide. However, the pathogenesis of T2DM has not yet been well explained. Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM. In this review, we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM. There is clear evidence that the intestinal microbiota influences the host through its effect on body weight, bile acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones. Modulating gut microbiota with the use of probiotics, prebiotics, antibiotics, and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host. Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM. Further studies may be able to boost the development of new effective therapeutic approaches for T2DM.

Gut microbes contribute to variation in solid organ transplant outcomes in mice.

PubMed

McIntosh, Christine M; Chen, Luqiu; Shaiber, Alon; Eren, A Murat; Alegre, Maria-Luisa

2018-05-25

Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics. We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival. These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft

The potential of gut microbiota and fecal volatile organic compounds analysis as early diagnostic biomarker for necrotizing enterocolitis and sepsis in preterm infants.

PubMed

Berkhout, Daniel Johannes Cornelis; Niemarkt, Hendrik Johannes; de Boer, Nanne Klaas Hendrik; Benninga, Marc Alexander; de Meij, Timotheüs Gualtherus Jacob

2018-05-01

Although the exact pathophysiological mechanisms of both necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants are yet to be elucidated, evidence is emerging that the gut microbiota plays a key role in their pathophysiology. Areas covered: In this review, initial microbial colonization and factors influencing microbiota composition are discussed. For both NEC and LOS, an overview of studies investigating preclinical alterations in gut microbiota composition and fecal volatile organic compounds (VOCs) is provided. Fecal VOCs are considered to reflect not only gut microbiota composition, but also their metabolic activity and concurrent interaction with the host. Expert review: Heterogeneity in study protocols and applied analytical techniques hampers reliable comparison between outcomes of different microbiota studies, limiting the ability to draw firm conclusions. This dilemma is illustrated by the finding that study results often cannot be reproduced, or even contradict each other. A NEC- and sepsis specific microbial or metabolic signature has not yet been discovered. Identification of 'disease-specific' VOCs and microbiota composition may increase understanding on pathophysiological mechanisms and may allow for development of an accurate screening tool, opening avenues towards timely identification and initiation of targeted treatment for preterm infants at increased risk for NEC and sepsis.

Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate

PubMed Central

Gallo, Antonella; Passaro, Giovanna; Gasbarrini, Antonio; Landolfi, Raffaele; Montalto, Massimo

2016-01-01

Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, PubMed was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn’s disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role. PMID:27621567

Can microbiota transplantation abrogate murine colonization resistance against Campylobacter jejuni?

PubMed

Heimesaat, M M; Plickert, R; Fischer, A; Göbel, U B; Bereswill, S

2013-03-01

Enterocolitis caused by Campylobacter jejuni represents an important socioeconomic burden worldwide. The host-specific intestinal microbiota is essential for maintaining colonization resistance (CR) against C. jejuni in conventional mice. Notably, CR is abrogated by shifts of the intestinal microbiota towards overgrowth with commensal E. coli during acute ileitis. Thus, we investigated whether oral transplantation (TX) of ileal microbiota derived from C. jejuni susceptible mice with acute ileitis overcomes CR of healthy conventional animals. Four days following ileitis microbiota TX or ileitis induction and right before C. jejuni infection, mice displayed comparable loads of main intestinal bacterial groups as shown by culture. Eight days following ileitis induction, but not ileal microbiota TX, however, C. jejuni could readily colonize the gastrointestinal tract of conventional mice and also translocate to extra-intestinal tissue sites such as mesenteric lymph nodes, spleen, liver, and blood within 4 days following oral infection. Of note, C. jejuni did not further deteriorate histopathology following ileitis induction. Lack of C. jejuni colonization in TX mice was accompanied by a decrease of commensal E. coli loads in the feces 4 days following C. jejuni infection. In summary, oral ileal microbiota TX from susceptible donors is not sufficient to abrogate murine CR against C. jejuni.

Effects of green tea consumption on human fecal microbiota with special reference to Bifidobacterium species.

PubMed

Jin, Jong-Sik; Touyama, Mutsumi; Hisada, Takayoshi; Benno, Yoshimi

2012-11-01

Green tea is one of the most popular beverages in the world. Its beneficial health effects and components have been extensively reviewed. However, little is known about the influence of green tea consumption on the human intestinal microbiota (HIM), which plays a crucial role in human health. Ten volunteers who did not usually consume green tea, drank it for 10 days and then stopped drinking it for 7 days. Their fecal samples were collected at three time points: before beginning the 10-day green-tea regime, at the conclusion of that 10 days, and 7 days after stopping the regime. Their fecal samples were analyzed by terminal restriction fragment length polymorphism with specific primer-restriction enzyme systems for HIM and by using a real-time PCR method for the Bifidobacterium species. Although the HIM of each subject was relatively stable, the proportion of Bifidobacterium species played an important role in the classification of their fecal microbiota. Although there were inter-individual differences in the Bifidobacterium species, an overall tendency for the proportion of bifidobacteria to increase because of green tea consumption was noted. However, little change was observed in the composition of Bifidobacterium species in each sample. This suggests that the change in proportion was induced, not by an inter-species transition, but by an intra-species increase and/or decrease. In conclusion, green tea consumption might act as a prebiotic and improve the colon environment by increasing the proportion of the Bifidobacterium species. © 2012 The Societies and Wiley Publishing Asia Pty Ltd.

Divergent Relationships between Fecal Microbiota and Metabolome following Distinct Antibiotic-Induced Disruptions.

PubMed

Choo, Jocelyn M; Kanno, Tokuwa; Zain, Nur Masirah Mohd; Leong, Lex E X; Abell, Guy C J; Keeble, Julie E; Bruce, Kenneth D; Mason, A James; Rogers, Geraint B

2017-01-01

The intestinal microbiome plays an essential role in regulating many aspects of host physiology, and its disruption through antibiotic exposure has been implicated in the development of a range of serious pathologies. The complex metabolic relationships that exist between members of the intestinal microbiota and the potential redundancy in functional pathways mean that an integrative analysis of changes in both structure and function are needed to understand the impact of antibiotic exposure. We used a combination of next-generation sequencing and nuclear magnetic resonance (NMR) metabolomics to characterize the effects of two clinically important antibiotic treatments, ciprofloxacin and vancomycin-imipenem, on the intestinal microbiomes of female C57BL/6 mice. This assessment was performed longitudinally and encompassed both antibiotic challenge and subsequent microbiome reestablishment. Both antibiotic treatments significantly altered the microbiota and metabolite compositions of fecal pellets during challenge and recovery. Spearman's correlation analysis of microbiota and NMR data revealed that, while some metabolites could be correlated with individual operational taxonomic units (OTUs), frequently multiple OTUs were associated with a significant change in a given metabolite. Furthermore, one metabolite, arginine, can be associated with increases/decreases in different sets of OTUs under differing conditions. Taken together, these findings indicate that reliance on shifts in one data set alone will generate an incomplete picture of the functional effect of antibiotic intervention. A full mechanistic understanding will require knowledge of the baseline microbiota composition, combined with both a comparison and an integration of microbiota, metabolomics, and phenotypic data. IMPORTANCE Despite the fundamental importance of antibiotic therapies to human health, their functional impact on the intestinal microbiome and its subsequent ability to recover are poorly

tuf Gene Sequence Variation in Bifidobacterium longum subsp. infantis Detected in the Fecal Microbiota of Chinese Infants.

PubMed

Lawley, Blair; Centanni, Manuela; Watanabe, Jun; Sims, Ian; Carnachan, Susan; Broadbent, Roland; Lee, Pheng Soon; Wong, Khai Hong; Tannock, Gerald W

2018-07-01

Members of the bacterial genus Bifidobacterium generally dominate the fecal microbiota of infants. The species Bifidobacterium longum is prevalent, but the B. longum subsp. longum and B. longum subsp. infantis strains that are known to colonize the infant bowel are not usually differentiated in microbiota investigations. These subspecies differ in their capacities to metabolize human milk oligosaccharides (HMO) and may have different ecological and symbiotic roles in humans. Quantitative PCR provides a quick analytical method by which to accurately ascertain the abundances of target species in microbiotas and microcosms. However, amplification targets in DNA extracted from samples need to be dependably differential. We evaluated the tuf gene sequence as a molecular target for quantitative PCR measurements of the abundances of B. longum subsp. infantis and B. longum subsp. longum in fecal microbiotas. This approach resulted in the detection of a tuf gene variant (operational taxonomic unit 49 [OTU49]) in Chinese infants that has sequence similarities to both B. longum subsp. infantis and B. longum subsp. longum We compared the genome sequence and growth and transcriptional characteristics of an OTU49 isolate cultured in HMO medium to those of other B. longum subsp. infantis cultures. We concluded from these studies that OTU49 belongs to B. longum subsp. infantis , that dependable quantitative PCR (qPCR) differentiation between the B. longum subspecies cannot be achieved by targeting tuf gene sequences, and that functional genes involved in carbohydrate metabolism might be better targets because they delineate ecological functions. IMPORTANCE High-throughput DNA sequencing methods and advanced bioinformatics analysis have revealed the composition and biochemical capacities of microbial communities (microbiota and microbiome), including those that inhabit the gut of human infants. However, the microbiology and function of natural ecosystems have received little

[Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome].

PubMed

Halmos, Tamás; Suba, Ilona

2016-01-03

The intestinal microbiota is well-known for a long time, but due to newly recognized functions, clinician's attention has turned to it again in the last decade. About 100 000 billion bacteria are present in the human intestines. The composition of bacteriota living in diverse parts of the intestinal tract is variable according to age, body weight, geological site, and diet as well. Normal bacteriota defend the organism against the penetration of harmful microorganisms, and has many other functions in the gut wall integrity, innate immunity, insulin sensitivity, metabolism, and it is in cross-talk with the brain functions as well. It's a recent recognition, that intestinal microbiota has a direct effect on the brain, and the brain also influences the microbiota. This two-way gut-brain axis consists of microbiota, immune and neuroendocrine system, as well as of the autonomic and central nervous system. Emerging from fermentation of carbohydrates, short-chain fatty acids develop into the intestines, which produce butyrates, acetates and propionates, having favorable effects on different metabolic processes. Composition of the intestinal microbiota is affected by the circadian rhythm, such as in shift workers. Dysruption of circadian rhythm may influence intestinal microbiota. The imbalance between the microbiota and host organism leads to dysbacteriosis. From the membrane of Gram-negative bacteria lipopolysacharides penetrate into the blood stream, via impaired permeability of the intestinal mucosa. These processes induce metabolic endotoxaemia, inflammation, impaired glucose metabolism, insulin resistance, obesity, and contribute to the development of metabolic syndrome, type 2 diabetes, inflammarory bowel diseases, autoimmunity and carcinogenesis. Encouraging therapeutic possibility is to restore the normal microbiota either using pro- or prebiotics, fecal transplantation or bariatric surgery. Human investigations seem to prove that fecal transplant from lean

Dietary Clostridium butyricum Induces a Phased Shift in Fecal Microbiota Structure and Increases the Acetic Acid-Producing Bacteria in a Weaned Piglet Model.

PubMed

Zhang, Jie; Chen, Xiyue; Liu, Ping; Zhao, Jinbiao; Sun, Jian; Guan, Wenyi; Johnston, Lee J; Levesque, Crystal L; Fan, Peixin; He, Ting; Zhang, Guolong; Ma, Xi

2018-05-23

Clostridium butyricum is known as a butyrate producer and a regulator of gut health, but whether it exerts a beneficial effect as a dietary supplement via modulating the intestinal microbiota remains elusive. This study investigated the impact of C. butyricum on the fecal microbiota composition and their metabolites 14 and 28 days after weaning with 10 g/kg dietary supplementation of C. butyricum. Dynamic changes of microbial compositions showed dramatically increasing Selenomonadales and decreasing Clostridiales on days 14 and 28. Within Selenomonadales, Megasphaera became the main responder by increasing from 3.79 to 11.31%. Following the prevalence of some acetate producers ( Magasphaera) and utilizers ( Eubacterium_hallii) at the genus level and even with a significant decrease in fecal acetate on day 28, the present data suggested that C. butyricum influenced microbial metabolism by optimizing the structure of microbiota and enhancing acetate production and utilization for butyrate production.

Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

PubMed Central

Zanella Terrier, Marie Céline; Simonet, Martine Louis; Bichard, Philippe; Frossard, Jean Louis

2014-01-01

Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability. PMID:24966611

Gut Microbiota as a Therapeutic Target for Metabolic Disorders.

PubMed

Okubo, Hirofumi; Nakatsu, Yusuke; Kushiyama, Akifumi; Yamamotoya, Takeshi; Matsunaga, Yasuka; Inoue, Masa-Ki; Fujishiro, Midori; Sakoda, Hideaki; Ohno, Haruya; Yoneda, Masayasu; Ono, Hiraku; Asano, Tomoichiro

2018-01-01

Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders. In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies. Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported. A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

PubMed

Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

2016-01-01

Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

Characterization of fecal microbiota across seven Chinese ethnic groups by quantitative polymerase chain reaction.

PubMed

Kwok, Lai-yu; Zhang, Jiachao; Guo, Zhuang; Gesudu, Qimu; Zheng, Yi; Qiao, Jianmin; Huo, Dongxue; Zhang, Heping

2014-01-01

The human gut microbiota consists of complex microbial communities, which possibly play crucial roles in physiological functioning and health maintenance. China has evolved into a multicultural society consisting of the major ethnic group, Han, and 55 official ethnic minority groups. Nowadays, these minority groups inhabit in different Chinese provinces and some of them still keep their unique culture and lifestyle. Currently, only limited data are available on the gut microbiota of these Chinese ethnic groups. In this study, 10 major fecal bacterial groups of 314 healthy individuals from 7 Chinese ethnic origins were enumerated by quantitative polymerase chain reaction. Our data confirmed that the selected bacterial groups were common to all 7 surveyed ethnicities, but the amount of the individual bacterial groups varied to different degree. By principal component and canonical variate analyses of the 314 individuals or the 91 Han subjects, no distinct group clustering pattern was observed. Nevertheless, weak differences were noted between the Han and Zhuang from other ethnic minority groups, and between the Heilongjiang Hans from those of the other provinces. Thus, our results suggest that the ethnic origin may contribute to shaping the human gut microbiota.

Characterization of Fecal Microbiota across Seven Chinese Ethnic Groups by Quantitative Polymerase Chain Reaction

PubMed Central

Guo, Zhuang; Gesudu, Qimu; Zheng, Yi; Qiao, Jianmin; Huo, Dongxue; Zhang, Heping

2014-01-01

The human gut microbiota consists of complex microbial communities, which possibly play crucial roles in physiological functioning and health maintenance. China has evolved into a multicultural society consisting of the major ethnic group, Han, and 55 official ethnic minority groups. Nowadays, these minority groups inhabit in different Chinese provinces and some of them still keep their unique culture and lifestyle. Currently, only limited data are available on the gut microbiota of these Chinese ethnic groups. In this study, 10 major fecal bacterial groups of 314 healthy individuals from 7 Chinese ethnic origins were enumerated by quantitative polymerase chain reaction. Our data confirmed that the selected bacterial groups were common to all 7 surveyed ethnicities, but the amount of the individual bacterial groups varied to different degree. By principal component and canonical variate analyses of the 314 individuals or the 91 Han subjects, no distinct group clustering pattern was observed. Nevertheless, weak differences were noted between the Han and Zhuang from other ethnic minority groups, and between the Heilongjiang Hans from those of the other provinces. Thus, our results suggest that the ethnic origin may contribute to shaping the human gut microbiota. PMID:24699404

Microbiota-based treatments in alcoholic liver disease.

PubMed

Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae

2016-08-07

Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD.

Fructooligosaccharides and fiber partially prevent the alterations in fecal microbiota and short-chain fatty acid concentrations caused by standard enteral formula in healthy humans.

PubMed

Whelan, Kevin; Judd, Patricia A; Preedy, Victor R; Simmering, Rainer; Jann, Alfred; Taylor, Moira A

2005-08-01

The intestinal microbiota are important during enteral tube feeding because they exert colonization resistance and produce SCFAs. However, the effect of the enteral formula composition on major bacterial groups of the microbiota has not been clearly defined. The aim of this study was to investigate the effect of enteral formulas with and without prebiotic fructooligosaccharides (FOS) and fiber on the fecal microbiota and SCFAs. Healthy subjects (n = 10; 4 men, 6 women) consumed both a standard enteral formula and one containing FOS (5.1 g/L) and fiber (8.9 g/L) as a sole source of nutrition for 14 d in a randomized, double-blind, crossover trial with a 6-wk washout phase. Fecal samples were collected at the start and end of each formula phase, and were analyzed for major bacterial groups and SCFA concentrations using fluorescent in situ hybridization and GLC, respectively. Although there were reductions in total fecal bacteria due to both formula treatments, concentrations were higher after the FOS/fiber formula period compared with the standard formula period (11.2 +/- 0.2 vs. 11.0 +/- 0.2 log(10) cells/g, P = 0.005). The FOS/fiber formula increased bifidobacteria (P = 0.004) and reduced clostridia (P = 0.006). Compared with the standard formula, the FOS/fiber formula resulted in higher concentrations of total SCFA (332.4 +/- 133.8 vs. 220.1 +/- 124.5 micromol/g, P = 0.022), acetate (219.6 +/- 96.3 vs. 136.8 +/- 74.5 micromol/g, P = 0.034) and propionate (58.4 +/- 37.4 vs. 35.6 +/- 25.5 micromol/g, P = 0.02). This study demonstrates that standard enteral formula leads to adverse alterations to the fecal microbiota and SCFA concentrations in healthy subjects, and these alterations are partially prevented by fortification of the formula with FOS and fiber.

Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke.

PubMed

Singh, Vikramjeet; Roth, Stefan; Llovera, Gemma; Sadler, Rebecca; Garzetti, Debora; Stecher, Bärbel; Dichgans, Martin; Liesz, Arthur

2016-07-13

Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome. We have identified a bidirectional communication along the brain-gut microbiota-immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome

Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy.

PubMed

Kang, Y; Cai, Y

2017-08-01

Hepatitis B is one of the most common infectious diseases globally. It has been estimated that there are 350 million chronic hepatitis B virus (HBV) carriers worldwide. The liver is connected to the small intestine by the bile duct, which carries bile formed in the liver to the intestine. Nearly all of the blood that leaves the stomach and intestines must pass through the liver. Human intestines contain a wide diversity of microbes, collectively termed the 'gut microbiota'. Gut microbiota play a significant role in host metabolic processes and host immune modulation, and influence host development and physiology (organ development). Altered gut microbiota is a common complication in liver disease. Changes in intestinal microbiota seem to play an important role in induction and promotion of HBV-induced chronic liver disease progression, and specific species among the intestinal commensal bacteria may play either a pathogenic or a protective role in the development of HBV-induced chronic liver disease. Thus, the gut microbiome may represent fertile targets for prevention or management of HBV-induced chronic liver disease. Faecal microbiota transplantation (FMT) may be a useful therapy for HBV-related disease in the future. However, the data available in this field remain limited, and relevant scientific work has only just commenced. New technologies have enabled systematic studies of gut microbiota, and provided more realistic information about its composition and pathological variance. This review summarizes the cutting edge of research into the relationship between gut microbiota and HBV-induced chronic liver disease, and the future prospects of FMT therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

78 FR 42965 - Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-18

... Microbiota for Transplantation To Treat Clostridium difficile Infection Not Responsive to Standard Therapies... Policy Regarding IND Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium... microbiota for transplantation (FMT) to treat C. difficile infection not responding to standard therapies...

Microbiota-targeted therapies on the intensive care unit.

PubMed

Haak, Bastiaan W; Levi, Marcel; Wiersinga, W Joost

2017-04-01

The composition and diversity of the microbiota of the human gut, skin, and several other sites is severely deranged in critically ill patients on the ICU, and it is likely that these disruptions can negatively affect outcome. We here review new and ongoing studies that investigate the use of microbiota-targeted therapeutics in the ICU, and provide recommendations for future research. Practically every intervention in the ICU as well as the physiological effects of critical illness itself can have a profound impact on the gut microbiota. Therapeutic modulation of the microbiota, aimed at restoring the balance between 'pathogenic' and 'health-promoting' microbes is therefore of significant interest. Probiotics have shown to be effective in the treatment of ventilator-associated pneumonia, and the first fecal microbiota transplantations have recently been safely and successfully performed in the ICU. However, all-encompassing data in this vulnerable patient group remain sparse, and only a handful of novel studies that study microbiota-targeted therapies in the ICU are currently ongoing. Enormous strides have been made in characterizing the gut microbiome of critically ill patients in the ICU, and an increasing amount of preclinical data reveals the huge potential of microbiota-targeted therapies. Further understanding of the causes and consequences of dysbiosis on ICU-related outcomes are warranted to push the field forward.

Clinical and immunologic effects of faecal microbiota transplantation in a patient with collagenous colitis

PubMed Central

Günaltay, Sezin; Rademacher, Lech; Hultgren Hörnquist, Elisabeth; Bohr, Johan

2017-01-01

One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC. PMID:28275312

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients

PubMed Central

Matijašić, Mario; Meštrović, Tomislav; Perić, Mihaela; Čipčić Paljetak, Hana; Panek, Marina; Vranešić Bender, Darija; Ljubas Kelečić, Dina; Krznarić, Željko; Verbanac, Donatella

2016-01-01

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms. PMID:27104515

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients.

PubMed

Matijašić, Mario; Meštrović, Tomislav; Perić, Mihaela; Čipčić Paljetak, Hana; Panek, Marina; Vranešić Bender, Darija; Ljubas Kelečić, Dina; Krznarić, Željko; Verbanac, Donatella

2016-04-19

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.

Therapeutic modulation of gut microbiota: current clinical applications and future perspectives.

PubMed

Ianiro, Gianluca; Bibbò, Stefano; Gasbarrini, Antonio; Cammarota, Giovanni

2014-01-01

Human beings and gut microbiota are in a symbiotic relationship, and the hypothesis of a "super organism" composed of the human organism and microbes has been recently proposed. The gut microbiota fulfills important metabolic and immunological tasks, and the impairment of its composition might alter homeostasis and lead to the development of microbiota-related diseases. The most common illnesses associated with alterations of the gut microbiota include inflammatory bowel disease, gastroenteric infections, irritable bowel syndrome and other gastrointestinal functional diseases, colorectal cancer, metabolic syndrome and obesity, liver diseases, allergic diseases, and neurological diseases such as autism. In theory, every disease associated with the impairment of intestinal microflora might benefit from the therapeutic modulation of the gut microbiota. A number of attempts to manipulate the microbiota have not produced identical results for every disease. Although antibiotics and probiotics have been available for a long time, the so-called fecal microbiota transplantation, which is a very old remedy, was only recently re-evaluated as a promising therapeutic approach for microbiota impairment. A comprehensive understanding of the gut microbiota composition, in states of both health and various diseases, is needed for the development of future approaches for microbiota modulation and for developing targeted therapies. In this review, we describe the role of the microbiota in several diseases and the related treatment options that are currently available.

The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

PubMed

West, Christina E; Renz, Harald; Jenmalm, Maria C; Kozyrskyj, Anita L; Allen, Katrina J; Vuillermin, Peter; Prescott, Susan L

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Metaproteogenomics Reveals Taxonomic and Functional Changes between Cecal and Fecal Microbiota in Mouse

PubMed Central

Tanca, Alessandro; Manghina, Valeria; Fraumene, Cristina; Palomba, Antonio; Abbondio, Marcello; Deligios, Massimo; Silverman, Michael; Uzzau, Sergio

2017-01-01

Previous studies on mouse models report that cecal and fecal microbial communities may differ in the taxonomic structure, but little is known about their respective functional activities. Here, we employed a metaproteogenomic approach, including 16S rRNA gene sequencing, shotgun metagenomics and shotgun metaproteomics, to analyze the microbiota of paired mouse cecal contents (CCs) and feces, with the aim of identifying changes in taxon-specific functions. As a result, Gram-positive anaerobes were observed as considerably higher in CCs, while several key enzymes, involved in oxalate degradation, glutamate/glutamine metabolism, and redox homeostasis, and most actively expressed by Bacteroidetes, were clearly more represented in feces. On the whole, taxon and function abundance appeared to vary consistently with environmental changes expected to occur throughout the transit from the cecum to outside the intestine, especially when considering metaproteomic data. The results of this study indicate that functional and metabolic differences exist between CC and stool samples, paving the way to further metaproteogenomic investigations aimed at elucidating the functional dynamics of the intestinal microbiota. PMID:28352255

Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients.

PubMed

Moreno-Indias, Isabel; Sánchez-Alcoholado, Lidia; Pérez-Martínez, Pablo; Andrés-Lacueva, Cristina; Cardona, Fernando; Tinahones, Francisco; Queipo-Ortuño, María Isabel

2016-04-01

This study evaluated the possible prebiotic effect of a moderate intake of red wine polyphenols on the modulation of the gut microbiota composition and the improvement in the risk factors for the metabolic syndrome in obese patients. Ten metabolic syndrome patients and ten healthy subjects were included in a randomized, crossover, controlled intervention study. After a washout period, the subjects consumed red wine and de-alcoholized red wine over a 30 day period for each. The dominant bacterial composition did not differ significantly between the study groups after the two red wine intake periods. In the metabolic syndrome patients, red wine polyphenols significantly increased the number of fecal bifidobacteria and Lactobacillus (intestinal barrier protectors) and butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) at the expense of less desirable groups of bacteria such as LPS producers (Escherichia coli and Enterobacter cloacae). The changes in gut microbiota in these patients could be responsible for the improvement in the metabolic syndrome markers. Modulation of the gut microbiota by using red wine could be an effective strategy for managing metabolic diseases associated with obesity.

Effect of preservation method on spider monkey (Ateles geoffroyi) fecal microbiota over 8 weeks.

PubMed

Hale, Vanessa L; Tan, Chia L; Knight, Rob; Amato, Katherine R

2015-06-01

Studies of the gut microbiome have become increasingly common with recent technological advances. Gut microbes play an important role in human and animal health, and gut microbiome analysis holds great potential for evaluating health in wildlife, as microbiota can be assessed from non-invasively collected fecal samples. However, many common fecal preservation protocols (e.g. freezing at -80 °C) are not suitable for field conditions, or have not been tested for long-term (greater than 2 weeks) storage. In this study, we collected fresh fecal samples from captive spider monkeys (Ateles geoffroyi) at the Columbian Park Zoo (Lafayette, IN, USA). The samples were pooled, homogenized, and preserved for up to 8 weeks prior to DNA extraction and sequencing. Preservation methods included: freezing at -20 °C, freezing at -80 °C, immersion in 100% ethanol, application to FTA cards, and immersion in RNAlater. At 0 (fresh), 1, 2, 4, and 8 weeks from fecal collection, DNA was extracted and microbial DNA was amplified and sequenced. DNA concentration, purity, microbial diversity, and microbial composition were compared across all methods and time points. DNA concentration and purity did not correlate with microbial diversity or composition. Microbial composition of frozen and ethanol samples were most similar to fresh samples. FTA card and RNAlater-preserved samples had the least similar microbial composition and abundance compared to fresh samples. Microbial composition and diversity were relatively stable over time within each preservation method. Based on these results, if freezers are not available, we recommend preserving fecal samples in ethanol (for up to 8weeks) prior to microbial extraction and analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Meta-Analysis of Fecal Microbiota and Metabolites in Experimental Colitic Mice during the Inflammatory and Healing Phases.

PubMed

Osaka, Toshifumi; Moriyama, Eri; Arai, Shunichi; Date, Yasuhiro; Yagi, Junji; Kikuchi, Jun; Tsuneda, Satoshi

2017-12-06

The imbalance of gut microbiota is known to be associated with inflammatory bowel disease, but it remains unknown whether dysbiosis is a cause or consequence of chronic gut inflammation. In order to investigate the effects of gut inflammation on microbiota and metabolome, the sequential changes in gut microbiota and metabolites from the onset of colitis to the recovery in dextran sulfate sodium-induced colitic mice were characterized by using meta 16S rRNA sequencing and proton nuclear magnetic resonance (¹H-NMR) analysis. Mice in the colitis progression phase showed the transient expansions of two bacterial families including Bacteroidaceae and Enterobacteriaceae and the depletion of major gut commensal bacteria belonging to the uncultured Bacteroidales family S24-7, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. After the initiation of the recovery, commensal Lactobacillus members promptly predominated in gut while other normally abundant bacteria excluding the Erysipelotrichaceae remained diminished. Furthermore, ¹H-NMR analysis revealed characteristic fluctuations in fecal levels of organic acids (lactate and succinate) associated with the disease states. In conclusion, acute intestinal inflammation is a perturbation factor of gut microbiota but alters the intestinal environments suitable for Lactobacillus members.

Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion*

PubMed Central

Wurm, Philipp; Spindelboeck, Walter; Krause, Robert; Plank, Johannes; Fuchs, Gottfried; Bashir, Mina; Petritsch, Wolfgang; Halwachs, Bettina; Langner, Cord; Högenauer, Christoph

2017-01-01

Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition. PMID:28333760

An altered gut microbiota in HIV infection: future prospective of FMT therapy.

PubMed

Kang, Yongbo; Cai, Yue

2018-06-07

Human immunodeficiency virus (HIV) infection progressively destroys CD4+ mononuclear cells leading to profound cellular immune deficiency that manifests as life threatening opportunistic infections and malignancies, i.e., the acquired immune deficiency syndrome (AIDS). Gut microbiota play key roles in the modulation of host metabolism and gene expression, maintenance of epithelial integrity, and mediation of inflammatory and immunity. Hence, the normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, a large number of studies have shown that the alteration of the gut microbiota contribute to the pathogenesis of several diseases, such as inflammatory bowel diseases, irritable bowel syndrome, metabolic diseases, anorexia nervosa, autoimmune diseases, multiple sclerosis, cancer, neuropsychiatric disorders, and cardiovascular diseases. Recently, accumulating evidences have has shed light on the association of dysbiosis of gut microbiota with HIV infection. Hence, the modification of gut microbiota may be a potential therapeutic tool. Fecal microbiota transplantation (FMT) may be a more straightforward and better therapy for HIV infection by manipulating the human intestinal bacteria. However, the relevant research is very limited, and large amount of scientific research work need to be done in the near further.

Comprehensive analysis of the fecal microbiota of healthy Japanese adults reveals a new bacterial lineage associated with a phenotype characterized by a high frequency of bowel movements and a lean body type.

PubMed

Oki, Kaihei; Toyama, Mutsumi; Banno, Taihei; Chonan, Osamu; Benno, Yoshimi; Watanabe, Koichi

2016-11-28

In Japan, a variety of traditional dietary habits and daily routines have developed in many regions. The effects of these behaviors, and the regional differences in the composition of the gut microbiota, are yet to be sufficiently studied. To characterize the Japanese gut microbiota and identify the factors shaping its composition, we conducted 16S metagenomics analysis of fecal samples collected from healthy Japanese adults residing in various regions of Japan. Each participant also completed a 94-question lifestyle questionnaire. We collected fecal samples from 516 healthy Japanese adults (325 females, 191 males; age, 21-88). Heatmap and biplot analyses based on the bacterial family composition of the fecal microbiota showed that subjects' region of residence or gender were not strongly correlated with the general composition of the fecal microbiota. Although clustering analysis for the whole cohort did not reveal any distinct clusters, two enterotype-like clusters were observed in the male, but not the female, subjects. In the whole subject population, the scores for bowel movement frequency were significantly correlated with the abundances of Christensenellaceae, Mogibacteriaceae, and Rikenellaceae in the fecal microbiota (P < 0.001). These three bacterial families were also significantly more abundant (P < 0.05 or 0.01) in lean subjects (body mass index (BMI) < 25) than in obese subjects (BMI > 30), which is consistent with previously published results. However, a previously reported correlation between BMI and bowel movement frequency was not observed. In addition, the abundances of these three families were positively correlated with each other and comprised a correlative network with 14 other bacterial families. The present study showed that the composition of the fecal microbiota of healthy Japanese adults at the national level was not strongly correlated with subjects' area of residence or gender. In addition, enterotype partitioning was

Microbiota-based treatments in alcoholic liver disease

PubMed Central

Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae

2016-01-01

Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD. PMID:27547010

Probiotic Lactobacillus rhamnosus GG Enhanced Th1 Cellular Immunity but Did Not Affect Antibody Responses in a Human Gut Microbiota Transplanted Neonatal Gnotobiotic Pig Model

PubMed Central

Wen, Ke; Tin, Christine; Wang, Haifeng; Yang, Xingdong; Li, Guohua; Giri-Rachman, Ernawati; Kocher, Jacob; Bui, Tammy; Clark-Deener, Sherrie; Yuan, Lijuan

2014-01-01

This study aims to establish a human gut microbiota (HGM) transplanted gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and diarrhea, and to verify the dose-effects of probiotics on HRV vaccine-induced immune responses. Our previous studies using the Gn pig model found that probiotics dose-dependently regulated both T cell and B cell immune responses induced by rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days starting at 12 hours after birth. We found that attenuated HRV (AttHRV) vaccination conferred similar overall protection against rotavirus diarrhea and virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the development of the neonatal immune system, as evidenced by the significantly enhanced IFN-γ producing T cell responses and reduction of regulatory T cells and their cytokine production in the AttHRV-vaccinated pigs. The higher dose Lactobacillus rhamnosus GG (LGG) feeding (14 doses, up to 109 colony-forming-unit [CFU]/dose) effectively increased the LGG counts in the HGM Gn pig intestinal contents and significantly enhanced HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 106 CFU/dose) was ineffective. Neither doses of LGG significantly improved the protection rate, HRV-specific IgA and IgG antibody titers in serum, or IgA antibody titers in intestinal contents compared to the AttHRV vaccine alone, suggesting that an even higher dose of LGG is needed to overcome the influence of the microbiota to achieve the immunostimulatory effect in the HGM pigs. This study demonstrated that HGM Gn pig is an applicable animal model for studying immune responses to rotavirus vaccines and can be used for studying interventions (i.e., probiotics and prebiotics) that may enhance the immunogenicity and protective efficacy of vaccines through improving the gut microbiota. PMID:24722168

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

PubMed

Landman, C; Quévrain, E

2016-06-01

The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

In vitro fermentation characteristics, in vivo ileal and total tract nutrient digestibilities, and fecal microbiota responses of dogs to α-cyclodextrin.

PubMed

Guevara, M A; Bauer, L L; Garleb, K A; Fahey, G C; de Godoy, M R C

2016-05-01

The objectives were to examine in vitro fermentation characteristics, in vivo nutrient digestibility, fecal microbiota, and serum lipid profiles as affected by α-cyclodextrin (ACD) supplementation. Short-chain fatty acid (SCFA) production was measured after in vitro fermentation for 3, 6, 9, and 12 h of ACD, β-cyclodextrin, and γ-cyclodextrin. Five mixed-breed hounds were used in a Latin square design. Each experimental period comprised 14 d, including 10 d for diet adaptation and 4 d for fecal collection. Dogs were fed, twice a day, an extruded diet made with poultry byproduct meal and brewer's rice as the main ingredients. Dogs were supplemented with 0, 1, 2, 3, or 4 g of ACD diluted in 15 mL of water twice daily for a total of 0, 2, 4, 6, and 8 g ACD/d. Maximal in vitro production of total SCFA was lowest for ACD. However, the greatest maximal production of propionate was noted for ACD treatment. Total tract nutrient digestibility and fecal DM concentration linearly decreased ( < 0.05) for treatment groups receiving ACD; no changes were observed for ileal digestibility. Serum cholesterol and triglyceride concentrations were within normal ranges for dogs and were not different among treatments. Similarly, no changes in fecal microbiota were observed. Overall, ACD supplementation appears to have no effect on nutrient absorption in the small intestine but may alter fermentation in the large bowel, which could lead to a higher proportion of propionate production as observed in the in vitro experiment.

Dynamics of fecal microbiota in hospitalized elderly fed probiotic LKM512 yogurt.

PubMed

Matsumoto, Mitsuharu; Sakamoto, Mitsuo; Benno, Yoshimi

2009-08-01

The comprehensive dynamics of intestinal microbiota including uncultured bacteria in response to probiotic consumption have not been well studied. The aims of this study were twofold: firstly to analyze the impact on intestinal microbiota of yogurt fermented by Bifidobacterium animalis subsp. lactis LKM512, Lactobacillus delbrueckii subsp. bulgaricus LKM1759, and Streptococcus thermophilus LKM1742 (LKM512 yogurt) and placebo fermented by these lactic acid bacterial strains without LKM512; and secondly to investigate the changes in intestinal microbiota that influence the concentration of PA, one of the beneficial metabolites produced by bacteria in the intestine. The LKM512 yogurt/placebo trial was performed in six hospitalized elderly patients (three men and three women with an average age of 80.3 years) and lasted seven weeks with the following schedule: pre-consumption for one week, LKM512 yogurt consumption for two weeks, washout period for two weeks, and placebo consumption for two weeks. The amount of ingested LKM512 yogurt or placebo was 100 g/day/individual. Fecal samples were analyzed using T-RFLP and real-time PCR. The T-RFLP patterns in five of the six volunteers were changed in a similar fashion by LKM512 yogurt consumption, although these patterns were individually changed following consumption of placebo. It was confirmed that B. animalis subsp. lactis was increased dramatically and Lactobacillus spp. tended to be decreased by LKM512 yogurt consumption. Some indigenous uncultured bacteria were increased and some decreased by LKM512 yogurt/placebo consumption. The similar changes in the intestinal microbiota of the elderly caused by consumption of the LKM512 yogurt were found to be influenced by the LKM512 strain itself, and not by the lactic acid bacteria in the yogurt. Moreover, this study suggests that the increase in intestinal PA concentrations caused by LKM512 yogurt consumption is probably dependent on the LKM512 strain colonizing the intestine.

In vitro fermentation of sulfated polysaccharides from E. prolifera and L. japonica by human fecal microbiota.

PubMed

Kong, Qing; Dong, Shiyuan; Gao, Jian; Jiang, Chaoyu

2016-10-01

In vitro fermentation of the sulfated polysaccharides from seaweeds Enteromorpha prolifera and Laminaria japonica and their prebiotic effects on human fecal microbiota were investigated in this study. The sulfated polysaccharides were fermented in vitro for 48h by human fecal cultures. When 0.8g MWCOL (polysaccharides MWCO<30kD) from L. japonica was fermented, the pH in fecal cultures decreased from 6.5 to 5.1 and the levels of short chain fatty acids, such as acetic, butyric and lactic acids all significantly increased. After 48h fermentation, 0.8g MWCOL showed good effect on modulating the gut microflora balance, because the beneficial strains (Lactobacillus and Bifidobacterium) were both significantly higher than those in control group (p<0.05). As far as we know, this is the first report that consumption of sulfated polysaccharides from E. prolifera and L. japonica is beneficial to the ecosystem of the intestinal tract by increasing the populations of probiotics and short chain fatty acids. Furthermore, our reports indicated that molecular weight of sulfated polysaccharide from marine algae is related to its prebiotic effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.

PubMed

Doki, Noriko; Suyama, Masahiro; Sasajima, Satoshi; Ota, Junko; Igarashi, Aiko; Mimura, Iyo; Morita, Hidetoshi; Fujioka, Yuki; Sugiyama, Daisuke; Nishikawa, Hiroyoshi; Shimazu, Yutaka; Suda, Wataru; Takeshita, Kozue; Atarashi, Koji; Hattori, Masahira; Sato, Eiichi; Watakabe-Inamoto, Kyoko; Yoshioka, Kosuke; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Takahashi, Naoto; Sakamaki, Hisashi; Honda, Kenya; Ohashi, Kazuteru

2017-09-01

Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.

Impact of gut microbiota on neurological diseases: Diet composition and novel treatments.

PubMed

Larroya-García, Ana; Navas-Carrillo, Diana; Orenes-Piñero, Esteban

2018-06-05

Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa.

Faecal microbiota transplantation: Where did it start? What have studies taught us? Where is it going?

PubMed

Chanyi, Ryan M; Craven, Laura; Harvey, Brandon; Reid, Gregor; Silverman, Michael J; Burton, Jeremy P

2017-01-01

The composition and activity of microorganisms in the gut, the microbiome, is emerging as an important factor to consider with regard to the treatment of many diseases. Dysbiosis of the normal community has been implicated in inflammatory bowel disease, Crohn's disease, diabetes and, most notoriously, Clostridium difficile infection. In Canada, the leading treatment strategy for recalcitrant C. difficile infection is to receive faecal material which by nature is filled with microorganisms and their metabolites, from a healthy individual, known as a faecal microbiota transplantation. This influx of bacteria into the gut helps to restore the microbiota to a healthy state, preventing C. difficile from causing further disease. Much of what is known with respect to the microbiota and faecal microbiota transplantation comes from animal studies simulating the human disease. Although these models allow researchers to perform studies that would be difficult in humans, they do not always recapitulate the human microbiome. This makes the translation of these results to humans somewhat questionable. The purpose of this review is to analyse these animal models and discuss the advantages and the disadvantages of them in relation to human translation. By understanding some of the limitation of animal models, we will be better able to design and perform experiments of most relevance to human applications.

454 pyrosequencing reveals a shift in fecal microbiota of healthy adult men consuming polydextrose or soluble corn fiber.

PubMed

Hooda, Seema; Boler, Brittany M Vester; Serao, Mariana C Rossoni; Brulc, Jennifer M; Staeger, Michael A; Boileau, Thomas W; Dowd, Scot E; Fahey, George C; Swanson, Kelly S

2012-07-01

The relative contribution of novel fibers such as polydextrose and soluble corn fiber (SCF) to the human gut microbiome and its association with host physiology has not been well studied. This study was conducted to test the impact of polydextrose and SCF on the composition of the human gut microbiota using 454 pyrosequencing and to identify associations among fecal microbiota and fermentative end-products. Healthy adult men (n = 20) with a mean dietary fiber (DF) intake of 14 g/d were enrolled in a randomized, double-blind, placebo-controlled crossover study. Participants consumed 3 treatment snack bars/d during each 21-d period that contained no supplemental fiber (NFC), polydextrose (PDX; 21 g/d), or SCF (21 g/d) for 21 d. There were no washout periods. Fecal samples were collected on d 16-21 of each period; DNA was extracted, followed by amplification of the V4-V6 region of the 16S rRNA gene using barcoded primers. PDX and SCF significantly affected the relative abundance of bacteria at the class, genus, and species level. The consumption of PDX and SCF led to greater fecal Clostridiaceae and Veillonellaceae and lower Eubacteriaceae compared with a NFC. The abundance of Faecalibacterium, Phascolarctobacterium, and Dialister was greater (P < 0.05) in response to PDX and SCF intake, whereas Lactobacillus was greater (P < 0.05) only after SCF intake. Faecalibacterium prausnitzii, well known for its antiinflammatory properties, was greater (P < 0.05) after fiber consumption. Principal component analysis clearly indicated a distinct clustering of individuals consuming supplemental fibers. Our data demonstrate a beneficial shift in the gut microbiome of adults consuming PDX and SCF, with potential application as prebiotics.

Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome.

PubMed

Ussar, Siegfried; Griffin, Nicholas W; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I; Kahn, C Ronald

2015-09-01

Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.

PubMed

Basson, Abigail R; Lam, Minh; Cominelli, Fabio

2017-12-01

The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

Fecal Transplantation Successfully Treats Recurrent D-Lactic Acidosis in a Child With Short Bowel Syndrome.

PubMed

Davidovics, Zev H; Vance, Katherine; Etienne, Nancy; Hyams, Jeffrey S

2017-07-01

D-lactic acidosis can occur in patients with short bowel syndrome (SBS) when excessive malabsorbed carbohydrate (CHO) enters the colon and is metabolized by colonic bacteria to D-lactate. D-lactate can be absorbed systemically, and increased serum levels are associated with central nervous system toxicity manifested by confusion, ataxia, and slurred speech. Current therapy, usually directed toward suppressing intestinal bacterial overgrowth and limiting ingested CHO, is not always successful. Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain. The exact mechanism of action is unknown, but it is surmised that the alteration of the intestinal microbiome, as well as the reintroduction of potential beneficial microbes, helps mediate disease. Here we present the case of a child with SBS and recurrent, debilitating D-lactic acidosis, which was successfully treated with fecal transplantation.

Unraveling the Fecal Microbiota and Metagenomic Functional Capacity Associated with Feed Efficiency in Pigs

PubMed Central

Yang, Hui; Huang, Xiaochang; Fang, Shaoming; He, Maozhang; Zhao, Yuanzhang; Wu, Zhenfang; Yang, Ming; Zhang, Zhiyan; Chen, Congying; Huang, Lusheng

2017-01-01

Gut microbiota plays fundamental roles in energy harvest, nutrient digestion, and intestinal health, especially in processing indigestible components of polysaccharides in diet. Unraveling the microbial taxa and functional capacity of gut microbiome associated with feed efficiency can provide important knowledge to improve pig feed efficiency in swine industry. In the current research, we studied the association of fecal microbiota with feed efficiency in 280 commercial Duroc pigs. All experimental pigs could be clustered into two enterotype-like groups. Different enterotypes showed the tendency of association with the feed efficiency (P = 0.07). We further identified 31 operational taxonomic units (OTUs) showing the potential associations with porcine feed efficiency. These OTUs were mainly annotated to the bacteria related to the metabolisms of dietary polysaccharides. Although we did not identify the RFI-associated bacterial species at FDR < 0.05 level, metagenomic sequencing analysis did find the distinct function capacities of gut microbiome between the high and low RFI pigs (FDR < 0.05). The KEGG orthologies related to nitrogen metabolism, amino acid metabolism, and transport system, and eight KEGG pathways including glycine, serine, and threonine metabolism were positively associated with porcine feed efficiency. We inferred that gut microbiota might improve porcine feed efficiency through promoting intestinal health by the SCFAs produced by fermenting dietary polysaccharides and improving the utilization of dietary protein. The present results provided important basic knowledge for improving porcine feed efficiency through modulating gut microbiome. PMID:28861066

Gut microbiota: A player in aging and a target for anti-aging intervention.

PubMed

Vaiserman, Alexander M; Koliada, Alexander K; Marotta, Francesco

2017-05-01

Aging-associated alterations in composition, diversity and functional features of intestinal microbiota are well-described in the modern literature. They are suggested to be caused by an age-related decline in immune system functioning (immunosenescence) and a low-grade chronic inflammation (inflammaging), which accompany many aging-associated pathologies. The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health and aging by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of fat deposition and metabolism and prevention of insulin resistance. Recently, a high effectiveness and safety of novel therapeutic application such as fecal microbiota transplantation in the prevention and treatment of age-related pathological conditions including atherosclerosis, type 2 diabetes and Parkinson's disease has been demonstrated. In this review, recent research findings are summarized on the role of gut micribiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in anti-aging medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Alteration in the Gut Microbiota Provokes Susceptibility to Tuberculosis.

PubMed

Khan, Nargis; Vidyarthi, Aurobind; Nadeem, Sajid; Negi, Shikha; Nair, Girish; Agrewala, Javed N

2016-01-01

The microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. In particular, they regulate immune homeostasis. Recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. Tuberculosis (TB) is the most devastating disease, inflicting mortality and morbidity. It remains unexplored, whether changes in the gut microbiota can provoke or prevent TB. In the current study, we have demonstrated the antibiotics driven changes in the gut microbial composition and their impact on the survival of Mycobacterium tuberculosis ( Mtb ) in the lungs, liver, and spleen of infected mice, compared to those with intact microbiota. Interestingly, dysbiosis of microbes showed significant increase in the bacterial burden in lungs and dissemination of Mtb to spleen and liver. Furthermore, elevation in the number of Tregs and decline in the pool of IFN-γ- and TNF-α-releasing CD4 T cells was noticed. Interestingly, fecal transplantation in the gut microbiota disrupted animals exhibited improved Th1 immunity and lesser Tregs population. Importantly, these animals displayed reduced severity to Mtb infection. This study for the first time demonstrated the novel role of gut microbes in the susceptibility to TB and its prevention by microbial implants. In future, microbial therapies may help in treating patients suffering from TB.

Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome.

PubMed

Tap, Julien; Derrien, Muriel; Törnblom, Hans; Brazeilles, Rémi; Cools-Portier, Stéphanie; Doré, Joël; Störsrud, Stine; Le Nevé, Boris; Öhman, Lena; Simrén, Magnus

2017-01-01

We have limited knowledge about the association between the composition of the intestinal microbiota and clinical features of irritable bowel syndrome (IBS). We collected information on the fecal and mucosa-associated microbiota of patients with IBS and evaluated whether these were associated with symptoms. We collected fecal and mucosal samples from adult patients who met the Rome III criteria for IBS at a secondary/tertiary care outpatient clinics in Sweden, as well as from healthy subjects. The exploratory set comprised 149 subjects (110 with IBS and 39 healthy subjects); 232 fecal samples and 59 mucosal biopsy samples were collected and analyzed by 16S ribosomal RNA targeted pyrosequencing. The validation set comprised 46 subjects (29 with IBS and 17 healthy subjects); 46 fecal samples, but no mucosal samples, were collected and analyzed. For each subject, we measured exhaled H 2 and CH 4 , oro-anal transit time, and the severity of psychological and gastrointestinal symptoms. Fecal methanogens were measured by quantitative polymerase chain reaction. Numerical ecology analyses and a machine learning procedure were used to analyze the data. Fecal microbiota showed covariation with mucosal adherent microbiota. By using classic approaches, we found no differences in fecal microbiota abundance or composition between patients with IBS vs healthy patients. A machine learning procedure, a computational statistical technique, allowed us to reduce the 16S ribosomal RNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units. We confirmed the robustness of the intestinal microbial signature for severe IBS in the validation set. The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects. By using this intestinal microbiota signature, we found IBS symptom severity to be associated negatively with microbial richness, exhaled CH 4 , presence

Impact of nutrition and rotavirus infection on the infant gut microbiota in a humanized pig model.

PubMed

Kumar, Anand; Vlasova, Anastasia N; Deblais, Loic; Huang, Huang-Chi; Wijeratne, Asela; Kandasamy, Sukumar; Fischer, David D; Langel, Stephanie N; Paim, Francine Chimelo; Alhamo, Moyasar A; Shao, Lulu; Saif, Linda J; Rajashekara, Gireesh

2018-06-22

Human rotavirus (HRV) is a major cause of viral gastroenteritis in infants; particularly in developing countries where malnutrition is prevalent. Malnutrition perturbs the infant gut microbiota leading to sub-optimal functioning of the immune system and further predisposing infants to enteric infections. Therefore, we hypothesized that malnutrition exacerbates rotavirus disease severity in infants. In the present study, we used a neonatal germ free (GF) piglets transplanted with a two-month-old human infant's fecal microbiota (HIFM) on protein deficient and sufficient diets. We report the effects of malnourishment on the HRV infection and the HIFM pig microbiota in feces, intestinal and systemic tissues, using MiSeq 16S gene sequencing (V4-V5 region). Microbiota analysis indicated that the HIFM transplantation resulted in a microbial composition in pigs similar to that of the original infant feces. This model was then used to understand the interconnections between microbiota diversity, diet, and HRV infection. Post HRV infection, HIFM pigs on the deficient diet had lower body weights, developed more severe diarrhea and increased virus shedding compared to HIFM pigs on sufficient diet. However, HRV induced diarrhea and shedding was more pronounced in non-colonized GF pigs compared to HIFM pigs on either sufficient or deficient diet, suggesting that the microbiota alone moderated HRV infection. HRV infected pigs on sufficient diet showed increased microbiota diversity in intestinal tissues; whereas, greater diversity was observed in systemic tissues of HRV infected pigs fed with deficient diet. These results suggest that proper nourishment improves the microbiota quality in the intestines, alleviates HRV disease and lower probability of systemic translocation of potential opportunistic pathogens/pathobionts. In conclusion, our findings further support the role for microbiota and proper nutrition in limiting enteric diseases.

Enteric microbiota leads to new therapeutic strategies for ulcerative colitis.

PubMed

Chen, Wei-Xu; Ren, Li-Hua; Shi, Rui-Hua

2014-11-14

Ulcerative colitis (UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition (termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrate-producing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractive approach for UC therapy. Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC. Such therapies include fecal microbiota transplantation, probiotics, prebiotics, antibiotics, helminth therapy, and dietary polyphenols, all of which can alter the abundance and composition of the enteric microbiota. Although there have been many large, randomized controlled clinical trials assessing these treatments, the effectiveness and safety of these bacteria-driven therapies need further evaluation. This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.

Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis.

PubMed

Thaiss, Christoph A; Zeevi, David; Levy, Maayan; Zilberman-Schapira, Gili; Suez, Jotham; Tengeler, Anouk C; Abramson, Lior; Katz, Meirav N; Korem, Tal; Zmora, Niv; Kuperman, Yael; Biton, Inbal; Gilad, Shlomit; Harmelin, Alon; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran

2014-10-23

All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic disturbances in humans with aberrant circadian rhythms, such as those documented in shift workers and frequent flyers.

Nutritional modulation of gut microbiota - the impact on metabolic disease pathophysiology.

PubMed

Ojeda, Patricia; Bobe, Alexandria; Dolan, Kyle; Leone, Vanessa; Martinez, Kristina

2016-02-01

The obesity epidemic afflicts over one third of the United States population. With few therapies available to combat obesity, a greater understanding of the systemic causes of this and other metabolic disorders is needed to develop new, effective treatments. The mammalian intestinal microbiota contributes to metabolic processes in the host. This review summarizes the research demonstrating the interplay of diet, intestinal microbiota and host metabolism. We detail the effects of diet-induced modifications in microbial activity and resultant impact on (1) sensory perception of macronutrients and total energy intake; (2) nutrient absorption, transport and storage; (3) liver and biliary function; (4) immune-mediated signaling related to adipose inflammation; and (5) circadian rhythm. We also discuss therapeutic strategies aimed to modify host-microbe interactions, including prebiotics, probiotics and postbiotics, as well as fecal microbiota transplantation. Elucidating the role of gut microbes in shaping metabolic homeostasis or dysregulation provides greater insight into disease development and a promising avenue for improved treatment of metabolic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterisation of Early-Life Fecal Microbiota in Susceptible and Healthy Pigs to Post-Weaning Diarrhoea

PubMed Central

Dou, Samir; Gadonna-Widehem, Pascale; Rome, Véronique; Hamoudi, Dounia; Rhazi, Larbi; Lakhal, Lyes; Larcher, Thibaut; Bahi-Jaber, Narges; Pinon-Quintana, Arturo; Guyonvarch, Alain

2017-01-01

Early-life microbial exposure is of particular importance to growth, immune system development and long-lasting health. Hence, early microbiota composition is a promising predictive biomarker for health and disease but still remains poorly characterized in regards to susceptibility to diarrhoea. In the present study, we aimed to assess if gut bacterial community diversity and composition during the suckling period were associated with differences in susceptibility of pigs to post-weaning diarrhoea. Twenty piglets from 5 sows (4 piglets / litter) were weaned in poor housing conditions to challenge their susceptibility to post-weaning diarrhoea. Two weeks after weaning, 13 pigs exhibited liquid faeces during 2 or 3 days and were defined as diarrhoeic (D) pigs. The other 7 pigs did not have diarrhea during the whole post-weaning experimental periodand were defined as healthy (H) pigs. Using a molecular characterisation of fecal microbiota with CE-SSCP fingerprint, Next Generation Sequencing and qPCR, we show that D and H pigs were mainly discriminated as early as postnatal day (PND) 7, i.e. 4 weeks before post-weaning diarrhoea occurence. At PND 7 H pigs displayed a lower evenness and a higher abundance of Prevotellaceae, Lachnospiraceae, Ruminocacaceae and Lactobacillaceae compared to D pigs. The sPLS regression method indicates that these bacterial families were strongly correlated to a higher Bacteroidetes abundance observed in PND 30 H pigs one week before diarrhoea. These results emphasize the potential of early microbiota diversity and composition as being an indicator of susceptibility to post-weaning diarrhoea. Furthermore, they support the health promoting strategies of pig herds through gut microbiota engineering. PMID:28072880

Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications: A case series.

PubMed

Lahtinen, Perttu; Mattila, Eero; Anttila, Veli-Jukka; Tillonen, Jyrki; Teittinen, Matti; Nevalainen, Pasi; Salminen, Seppo; Satokari, Reetta; Arkkila, Perttu

2017-10-21

Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli ( E. coli ) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

PubMed Central

Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of

Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.

PubMed

Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further

Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats

PubMed Central

Wang, Jing-Hua; Kim, Bong-Soo; Han, Kyungsun; Kim, Hojun

2017-01-01

Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid. PMID:28545248

Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

PubMed

Wang, Jing-Hua; Kim, Bong-Soo; Han, Kyungsun; Kim, Hojun

2017-05-23

Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid.

Temporal Stability and the Effect of Transgenerational Transfer on Fecal Microbiota Structure in a Long Distance Migratory Bird

PubMed Central

Kreisinger, Jakub; Kropáčková, Lucie; Petrželková, Adéla; Adámková, Marie; Tomášek, Oldřich; Martin, Jean-François; Michálková, Romana; Albrecht, Tomáš

2017-01-01

Animal bodies are inhabited by a taxonomically and functionally diverse community of symbiotic and commensal microorganisms. From an ecological and evolutionary perspective, inter-individual variation in host-associated microbiota contributes to physiological and immune system variation. As such, host-associated microbiota may be considered an integral part of the host’s phenotype, serving as a substrate for natural selection. This assumes that host-associated microbiota exhibits high temporal stability, however, and that its composition is shaped by trans-generational transfer or heritable host-associated microbiota modulators encoded by the host genome. Although this concept is widely accepted, its crucial assumptions have rarely been tested in wild vertebrate populations. We performed 16S rRNA metabarcoding on an extensive set of fecal microbiota (FM) samples from an insectivorous, long-distance migratory bird, the barn swallow (Hirundo rustica). Our data revealed clear differences in FM among juveniles and adults as regards taxonomic and functional composition, diversity and co-occurrence network complexity. Multiple FM samples from the same juvenile or adult collected within single breeding seasons exhibited higher similarity than expected by chance, as did adult FM samples over two consecutive years. Despite low effect sizes for FM stability over time at the community level, we identified an adult FM subset with relative abundances exhibiting significant temporal consistency, possibly inducing long-term effects on the host phenotype. Our data also indicate a slight maternal (but not paternal) effect on FM composition in social offspring, though this is unlikely to persist into adulthood. We discuss our findings in the context of both evolution and ecology of microbiota vs. host interactions and barn swallow biology. PMID:28220109

Gut microbiota directs PPARγ-driven reprogramming of the liver circadian clock by nutritional challenge.

PubMed

Murakami, Mari; Tognini, Paola; Liu, Yu; Eckel-Mahan, Kristin L; Baldi, Pierre; Sassone-Corsi, Paolo

2016-09-01

The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high-fat diet, the gut microbiota drives PPARγ-mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPARγ-driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism. © 2016 The Authors.

Flammulina velutipes polysaccharides improve scopolamine-induced learning and memory impairment in mice by modulating gut microbiota composition.

PubMed

Su, Anxiang; Yang, Wenjian; Zhao, Liyan; Pei, Fei; Yuan, Biao; Zhong, Lei; Ma, Gaoxing; Hu, Qiuhui

2018-03-01

Flammulina velutipes polysaccharides (FVP) have been proved to be effective in improving learning and memory impairment in mice. However, their underlying mechanism remains unclear. The aim of this study was to investigate the relationship between memory improvement and gut microbiota regulation of FVP. The results showed a significant decrease in the relative abundances of Clostridia and Bacilli but a significant increase in Bacteroidia, Erysipelotrichia and Actinobacteria in the FVP-treated group versus the control group. Fecal microbiota transplantation of mice with 'FVP microbiota' derived from FVP-fed mice resulted in improved learning and memory function compared to colonization with 'common microbiota' derived from control individuals. FVP and 'FVP microbiota' significantly increased the numbers of platform crossings and the swimming distance of mice in the probe test and decreased the escape latency and total swimming distance of mice in the hidden platform test. Moreover, FVP and 'FVP microbiota' regulated cytokines, such as IL-1β, TNF-α, IL-6 and IL-10, suggesting a mechanism involving the suppression of neuroinflammation. This study indicated that the regulation of the gut microbiome may have a causal role in improving scopolamine-induced impairment of learning and memory.

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

Pharmabiotic Manipulation of the Microbiota in Gastrointestinal Disorders: A Clinical Perspective.

PubMed

Giron, Fanny; Quigley, Eamonn M M

2018-04-24

The advent and widespread availability of high-throughput technology has revolutionized the assessment of the communities of microorganisms that inhabit the gastrointestinal tract - the gut microbiota. As our understanding of the role of the microbiota in health and human disease increases so to do efforts to prevent and treat disease through the modulation of the microbiota. Several strategies are available to us and range from time honored approaches, such as antibiotics and probiotics, to changes in diet, the administration of prebiotics as food supplements and fecal microbiota transplantation. Of these, diet is perhaps the most pervasive but often ignored modulator of the microbiota and a failure to recognize its impact complicates the interpretation of many microbiota studies. The impacts of antibiotics on the microbiotia are more complex than originally thought and, though antibiotics can be life-saving, their effects on commensal bacterial populations can have devastating consequences. Though there have been many studies of, and even more claims made for, probiotics, the majority of available studies suffer from significant deficits in study design and execution and many claims remain to be substantiated. Though holding much promise, the study of prebiotics in human disease is still in its infancy. Possibilities other than the administration of live organisms have been identified through efforts to mine the microbiota for novel therapeutics and include dead organisms, bacterial components, small molecules elaborated by bacteria and even bacterial DNA; the term pharmabiotic has been introduced to encompass the full range of therapeutic possibilities that the microbiota offers.

Microbial taxonomic and metabolic alterations during faecal microbiota transplantation to treat Clostridium difficile infection.

PubMed

Kellingray, Lee; Gall, Gwénaëlle Le; Defernez, Marianne; Beales, Ian L P; Franslem-Elumogo, Ngozi; Narbad, Arjan

2018-05-07

This study aimed to examine changes to the microbiota composition and metabolic profiles of seven patients with recurrent Clostridium difficile infection (rCDI), following treatment with faecal microbiota transplant (FMT). 16S rDNA sequencing and 1 H NMR were performed on faecal samples from the patients (pre-, post-FMT, and follow-up) and the associated donor samples. Sparse partial-least-square analysis was used to identify correlations between the two datasets. The patients' microbiota post-FMT tended to shift towards the donor microbiota, specifically through proportional increases of Bacteroides, Blautia, and Ruminococcus, and proportional decreases of Enterococcus, Escherichia, and Klebsiella. However, although cured of infection, one patient, who suffers from chronic alcohol abuse, retained the compositional characteristics of the pre-FMT microbiota. Following FMT, increased levels of short-chain fatty acids, particularly butyrate and acetate, were observed in all patients. Sparse partial-least-square analysis confirmed a positive correlation between butyrate and Bacteroides, Blautia, and Ruminococcus, with a negative correlation between butyrate and Klebsiella and Enterococcus. Clear differences were observed in the microbiota composition and metabolic profiles between donors and rCDI patients, which were largely resolved in patients following FMT. Increased levels of butyrate appear to be a factor associated with resolution of rCDI. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of Oral Administration of Metronidazole or Prednisolone on Fecal Microbiota in Dogs

PubMed Central

Ohno, Koichi; Horigome, Ayako; Odamaki, Toshitaka; Tsujimoto, Hajime

2014-01-01

Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further

In vitro fermentation of mulberry fruit polysaccharides by human fecal inocula and impact on microbiota.

PubMed

Chen, Chun; Huang, Qiang; Fu, Xiong; Liu, Rui Hai

2016-11-09

This study investigated the in vitro fermentation of polysaccharides from Morus alba L., the contribution of its carbohydrates to the fermentation, and the effect on the composition of gut microbiota. Over 48 h of fermentation, the pH value in the fecal culture decreased from 7.12 to 6.14, and the total short chain fatty acids (SCFA) and acetic, propionic, and butyric acids all significantly increased. After 48 h of fermentation, 45.36 ± 1.36% of the total carbohydrates in the polysaccharide, including 35.72 ± 1.51% of arabinose, 23.1 ± 1.19% of galactose, 41.43 ± 1.52% of glucose, 26.36 ± 1.93% of rhamnose and 65.57 ± 1.07% of galacturic acid, were consumed. The increase in acetic and butyric acids was primarily due to the fermentation of galactose and galacturonic acid in the polysaccharide, while the increase in propionic acid resulted mainly from the fermentation of arabinose and glucose. In addition, the polysaccharide could modulate the gut microbiota composition by increasing the Bacteroidetes population and decreasing the Firmicutes population. The results may facilitate the development of food products known as prebiotics, aimed at improving gastrointestinal health.

Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women.

PubMed

Ott, Beate; Skurk, Thomas; Hastreiter, Ljiljana; Lagkouvardos, Ilias; Fischer, Sandra; Büttner, Janine; Kellerer, Teresa; Clavel, Thomas; Rychlik, Michael; Haller, Dirk; Hauner, Hans

2017-09-20

Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.

Gut microbiota: a key player in health and disease. A review focused on obesity.

PubMed

Villanueva-Millán, M J; Pérez-Matute, P; Oteo, J A

2015-09-01

Gut microbiota, its evolutive dynamics and influence on host through its protective, trophic and metabolic actions, has a key role in health and opens unique opportunities for the identification of new markers of the physiopathological state of each individual. Alterations in gut microbiota composition have been associated with plenty disorders. Of interest, the vast number of studies demonstrates the role of microbiota in obesity, a serious public health problem that has reached epidemic proportions in many developed and middle-income countries. The economic and health costs of this condition and its comorbidities such as fatty liver, insulin resistance/diabetes, or cardiovascular events are considerable. Therefore, every strategy designed to reduce obesity would imply important savings. Targeting microbiota, in order to restore/modulate the microbiota composition with antibiotics, probiotics, prebiotics, or even fecal transplants, is considered as a promising strategy for the development of new solutions for the treatment of obesity. However, there is still lot to do in this field in order to identify the exact composition of microbiota in "health" and the specific mechanisms that regulate the host-microbiotal crosstalk. In addition, it is important to note that changes not only in the gut microbiota profile (abundance) but also in its metabolism and functions need to be taken into account in the context of contribution in the physiopathology of obesity and related disorders.

Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance?

PubMed

Nettleton, Jodi E; Reimer, Raylene A; Shearer, Jane

2016-10-01

Disruption in the gut microbiota is now recognized as an active contributor towards the development of obesity and insulin resistance. This review considers one class of dietary additives known to influence the gut microbiota that may predispose susceptible individuals to insulin resistance - the regular, long-term consumption of low-dose, low calorie sweeteners. While the data are controversial, mounting evidence suggests that low calorie sweeteners should not be dismissed as inert in the gut environment. Sucralose, aspartame and saccharin, all widely used to reduce energy content in foods and beverages to promote satiety and encourage weight loss, have been shown to disrupt the balance and diversity of gut microbiota. Fecal transplant experiments, wherein microbiota from low calorie sweetener consuming hosts are transferred into germ-free mice, show that this disruption is transferable and results in impaired glucose tolerance, a well-known risk factor towards the development of a number of metabolic disease states. As our understanding of the importance of the gut microbiota in metabolic health continues to grow, it will be increasingly important to consider the impact of all dietary components, including low calorie sweeteners, on gut microbiota and metabolic health. Copyright © 2016 Elsevier Inc. All rights reserved.

In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota.

PubMed

Martin, Glynn; Kolida, Sofia; Marchesi, Julian R; Want, Elizabeth; Sidaway, James E; Swann, Jonathan R

2018-01-01

Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel in vitro approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing. Anaerobic, pH-controlled batch cultures were inoculated with human fecal microbiota and treated with individual conjugated primary bile acids (500 μg/ml) to serve as the sole substrate for 24 h. Samples were collected throughout the experiment (0, 5, 10, and 24 h) and the bacterial composition was determined by 16S rRNA gene sequencing and the bile acid signatures were characterized using a targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) approach. Data fusion techniques were used to identify statistical bacterial-metabolic linkages. An increase in gut bacteria associated bile acids was observed over 24 h with variation in the rate of bile acid metabolism across the volunteers ( n = 7). Correlation analysis identified a significant association between the Gemmiger genus and the deconjugation of glycine conjugated bile acids while the deconjugation of taurocholic acid was associated with bacteria from the Eubacterium and Ruminococcus genera. A positive correlation between Dorea and deoxycholic acid production suggest a potential role for this genus in cholic acid dehydroxylation. A slower deconjugation of taurocholic acid was observed in individuals with a greater abundance of Parasutterella and Akkermansia . This work demonstrates the utility of integrating compositional (metataxonomics) and functional (metabonomics) systems biology approaches

Correlations of Fecal Metabonomic and Microbiomic Changes Induced by High-fat Diet in the Pre-Obesity State

NASA Astrophysics Data System (ADS)

Lin, Hong; An, Yanpeng; Hao, Fuhua; Wang, Yulan; Tang, Huiru

2016-02-01

Obesity resulting from interactions of genetic and environmental factors becomes a serious public health problem worldwide with alterations of the metabolic phenotypes in multiple biological matrices involving multiple metabolic pathways. To understand the contributions of gut microbiota to obesity development, we analyzed dynamic alterations in fecal metabonomic phenotype using NMR and fecal microorganism composition in rats using pyrosequencing technology during the high-fat diet (HFD) feeding for 81 days (pre-obesity state). Integrated analysis of these two phenotypic datasets was further conducted to establish correlations between the altered rat fecal metabonome and gut microbiome. We found that one-week HFD feeding already caused significant changes in rat fecal metabonome and such changes sustained throughout 81-days feeding with the host and gut microbiota co-metabolites clearly featured. We also found that HFD caused outstanding decreases in most fecal metabolites implying enhancement of gut absorptions. We further established comprehensive correlations between the HFD-induced changes in fecal metabonome and fecal microbial composition indicating contributions of gut microbiota in pathogenesis and progression of the HFD-induced obesity. These findings provided essential information about the functions of gut microbiota in pathogenesis of metabolic disorders which could be potentially important for developing obesity prevention and treatment therapies.

Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis.

PubMed

Grąt, M; Wronka, K M; Krasnodębski, M; Masior, Ł; Lewandowski, Z; Kosińska, I; Grąt, K; Stypułkowski, J; Rejowski, S; Wasilewicz, M; Gałęcka, M; Szachta, P; Krawczyk, M

2016-06-01

Changes within the gut microbiota contribute to the progression of chronic liver diseases. According to the results of several studies performed in animal models, gut dysbiosis plays an important role in hepatocarcinogenesis. The aim of this study was to explore the characteristics of gut microbiota associated with the presence of hepatocellular cancer (HCC) in patients with cirrhosis of the liver undergoing liver transplantation. A total of 15 patients with HCC and 15 non-HCC patients matched according to etiology of cirrhosis and Model for End-Stage Liver Disease (MELD) scores who underwent liver transplantations between 2012 and 2014 were included. Analysis of their gut microbial profile was based on prospectively collected stool samples from the pretransplant period. Patients with and without HCC were similar with respect to age (P = .506), sex (P = .700), hepatitis C virus (P > .999) and hepatitis B virus (P = .715) infection status, alcoholic liver disease (P > .999), and MELD score (P = .337). Notably, the presence of HCC was associated with significantly increased fecal counts of Escherichia coli (P = .025). Prediction of HCC presence based on E coli counts was associated with the area under the receiver-operating curve of 0.742 (95% confidence interval, 0.564-0.920), with the optimal cutoff on the level of 17.728 (natural logarithm of colony-forming units per 1 g of feces). Sensitivity and specificity rates for the established cutoff were 66.7% and 73.3%, respectively. The profile of gut microbiota associated with the presence of HCC in cirrhotic patients is characterized by increased fecal counts of E coli. Therefore, intestinal overgrowth of E coli may contribute to the process of hepatocarcinogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety and efficacy of encapsulated fecal microbiota transplantation for recurrent Clostridium difficile infection: a systematic review.

PubMed

Iqbal, Umair; Anwar, Hafsa; Karim, Muhammad A

2018-07-01

Fecal microbial transplantation (FMT) has been shown to be effective for the treatment of recurrent clostridium difficile infection (CDI). The efficacy and safety of freeze-dried encapsulated FMT for the treatment of recurrent CDI is unclear. We performed a systematic review to evaluate and analyze the current evidence in this respect. A systematic literature search was performed using the PubMed, Embase, and Medline databases until December 2017 to identify all original studies that investigated the role of administration of encapsulated FMT in recurrent CDI. The study included patients of all ages. Two independent reviewers extracted data and assessed the quality of publications; a third investigator resolved any discrepancies. A total of six studies, five case series and one randomized-controlled trial, were included in this review. Overall, 341 patients completed treatment with encapsulated FMT. Only three major adverse events were reported and no deaths occurred directly related to FMT. In all, 285 patients responded to the first treatment, with no recurrence during the specified follow-up period set to meet the primary endpoint. Forty-two patients underwent a second treatment, with resolution of symptoms in 28 patients. At least five patients were reported to undergo a third treatment, with resolution in three of them. Only one patient was reported to have received four treatments without long-term resolution of symptoms. Low-quality to moderate-quality evidence showed that encapsulated FMT is safe and cost-effective for the treatment and prevention of recurrent CDI. Its efficacy is not inferior to FMT performed through the nonoral route. Randomized-controlled trials are necessary to compare its efficacy with oral antimicrobial drugs and also to evaluate the potential adverse effects associated with the treatment.

Technical Aspects of Fecal Microbial Transplantation (FMT).

PubMed

Bhutiani, N; Schucht, J E; Miller, K R; McClave, Stephen A

2018-06-09

Fecal microbial transplantation (FMT) has become established as an effective therapeutic modality in the treatment of antibiotic-refractory recurrent Clostridium difficile colitis. A number of formulations and methods of delivery of FMT are currently available, each with distinct advantages. This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice. FMT can be obtained in fresh, frozen, lyophilized, and capsule-based formulations for delivery by oral ingestion, nasoenteric tube, colonoscopy, or enema (depending on the formulation used). Choosing the optimal method relies heavily on patient-related factors, including underlying pathology and severity of illness. As potential applications for FMT expand, careful donor screening and patient selection are critical to minimizing risk to patients and physicians. FMT represents an excellent therapeutic option for treatment of recurrent Clostridium difficile colitis and holds promise as a possible treatment modality in a variety of other conditions. The wide array of delivery methods allows for its application in various disease states in both the inpatient and outpatient setting.

Targeting the microbiota in the management of gastrointestinal and liver disease.

PubMed

Quigley, Eamonn M M; Monsour, Howard P

2013-01-01

Thanks to rapid advances in technology the details of the human microbiome and its functions in health and disease are being progressively revealed. Though many reports have linked various disease states with an altered microbiome and while some associations between the microbiome and disease states are well established, many of these studies are largely descriptive and the changes reported in the microbiome have yet to be shown to be causative. A number of strategies are available to modify the microbiota; some such as the use of antibiotics for specific indications, are well established, others such as the use of probiotics and prebiotics in a variety of disease states are supported by more limited data. Fecal transplantation has emerged as an exciting, albeit rather drastic, intervention for intestinal and, perhaps, other disorders. Other approaches, such as the isolation, purification and formulation of small molecules with specific biological actions, derived from the microbiota look very promising.

Intestinal microbiota and innate immunity-related gene alteration in cirrhotic rats with liver transplantation.

PubMed

Xie, Y R; Liu, S L; Liu, X; Luo, Z B; Zhu, B; Li, Z F; Li, L J; He, Y; Jiang, L; Li, H; Ruan, B

2011-12-01

The present study investigated the alteration of intestinal microbiota, innate immunity-related genes, and bacterial translocation in rats with cirrhosis and liver transplantation. Specific pathogen-free Sprague-Dawley rats were randomized into 4 groups: (1) normal controls (N); (2) liver cirrhosis (LC); (3) normal control groups with liver transplantation (LTN); and (4) liver cirrhosis with liver transplantation (LTC). We examined plasma endotoxin, bacterial tacslocation, denaturing gradient gel electrophoresis (DGGE) profile of intestinal mucosa-associated bacteria, abundance of key bacterial populations, and expression of innate immunity-related gene. The LTC and LC group, showed higher endotoxin levels (1.08±0.73 EU/mL and 0.74±0.70 EU/mL, respectively) than the N group (0.27±0.13 EU/mL; P<.05). the incidence of bacterial translocation (BT) to liver and mesenteric lymph nodes (MLN), and the number of total bacteria were increased significantly in the LTC and LC groups compared with the N group (P<.05). The counts of Lactobacilli and Bacteroides were lower, whereas Enterobacteria were higher in the LC than the N group (P<.05). Mucins (MUC2, MUC3) and Toll-like receptors (TLR2, TLR4) messenger RNA (mRNA) expression were significantly higher in the LC and LTC groups than the N group (P<.05). The marked difference between the groups in the overall structure of the bacterial community was also generated by DGGE profiles. Liver cirrhosis disturbs intestinal microbiota and innate immunity-related genes, which contributes to endotoxemia and bacterial translocation. These had not completely recovered in cirrhotic rats until 1 month after orthotopic liver transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

In vitro effect of dietary protein level and nondigestible oligosaccharides on feline fecal microbiota.

PubMed

Pinna, C; Stefanelli, C; Biagi, G

2014-12-01

The aim of the present study was to evaluate in vitro the effect of some prebiotic substances and 2 dietary protein levels on the composition and activity of feline fecal microbiota. Two in vitro studies were conducted. First, 6 nondigestible oligosaccharides were studied; treatments were control diet (CTRL), gluconic acid (GA), carrot fiber (CF), fructooligosaccharides (FOS), galactooligosaccharides (GOS), lactitol (LAC), and pectins from citrus fruit (PEC). Substrates were added to feline fecal cultures at 2 g/L for 24 h incubation. Compared with the CTRL, ammonia had been reduced (P<0.05) by GOS (-9%) after 6 h and by GA (-14%), LAC (-12%), and PEC (-10%) after 24 h. After 24 h, all treatments had resulted in a lower pH versus the CTRL. Putrescine concentrations at 24 h were greater (P<0.05) in cultures treated with FOS (+90%), GOS (+96%), and LAC (+87%). Compared with the CTRL, total VFA were higher (P<0.05) in bottles containing CF (+41%), whereas the acetic to propionic acid ratio was reduced by LAC (-51%; P<0.05). After 24 h, Enterobacteriaceae had been reduced (P<0.05) by LAC and PEC. In a second study, LAC and FOS were selected to be tested in the presence of 2 diets differing in their protein content. There were 6 treatments: low-protein (LP) CTRL with no addition of prebiotics (CTRL-LP), high-protein (HP) CTRL with no addition of prebiotics (CTRL-HP), LP diet plus FOS, CTRL-HP plus FOS, LP diet plus LAC, and CTRL-HP plus LAC. Both FOS and LAC were added to feline fecal cultures at 2 g/L for 24 h incubation. Ammonia at 24 h was affected (P<0.05) by the protein level (36.2 vs. 50.2 mmol/L for LP and HP, respectively). The CTRL-HPs resulted in a higher pH and increased concentrations of biogenic amines were found after 6 and 24 h of incubation (P<0.05); putrescine at 24 h showed an increase (P<0.05) in cultures treated with FOS. Total VFA were influenced (P<0.05) by the protein level (40.9 vs. 32.6 mmol/L for LP and HP, respectively). At 24 h, the CTRL

Ionic liquid-based reagents improve the stability of midterm fecal sample storage.

PubMed

Hao, Lilan; Xia, Zhongkui; Yang, Huanming; Wang, Jian; Han, Mo

2017-08-01

Fecal samples are widely used in metagenomic research, which aims to elucidate the relationship between human health and the intestinal microbiota. However, the best conditions for stable and reliable storage and transport of these samples at room temperature are still unknown, and whether samples stored at room temperature for several days will maintain their microbiota composition is still unknown. Here, we established and tested a preservation method using reagents containing imidazolium- or pyridinium-based ionic liquids. We stored human fecal samples in these reagents for up to 7 days at different temperatures. Subsequently, all samples were sequenced and compared with fresh samples and/or samples treated under other conditions. The 16S rRNA sequencing results suggested that ionic liquid-based reagents could stabilize the composition of the microbiota in fecal samples during a 7-day storage period, particularly when stored at room temperature. Thus, this method may have implications in the storage of fecal samples for metagenomic research. Copyright © 2017 Elsevier B.V. All rights reserved.

The fecal microbiome of ALS patients.

PubMed

Brenner, David; Hiergeist, Andreas; Adis, Carolin; Mayer, Benjamin; Gessner, André; Ludolph, Albert C; Weishaupt, Jochen H

2018-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disease accompanied by both systemic and central nervous system-specific inflammation as well as deregulated energy metabolism. These potential pathogenetic factors have recently been found to mutually interact with the gut microbiota, raising the hypothesis of a link between microbiome alterations and ALS pathogenesis. The aim of our study was to assess whether ALS is associated with an altered composition of the fecal microbiota. We compared the fecal microbiota of 25 ALS patients with 32 age- and gender-matched healthy persons using 16S rRNA gene sequencing analysis. Confounding factors and secondary disease effects on the microbiome were minimized by selection of patients without dysphagia, gastrostomy, noninvasive ventilation, or reduced body mass index. Comparing the 2 carefully matched groups, the diversity and the abundance of the bacterial taxa on the different taxonomic levels as well as PICRUSt-predicted metagenomes were almost indistinguishable. Significant differences between ALS patients and healthy controls were only observed with regard to the overall number of microbial species (operational taxonomic units) and in the abundance of uncultured Ruminococcaceae. Conclusively, ALS patients do not exhibit a substantial alteration of the gut microbiota composition. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

[Microbiota and representations of the human body].

PubMed

Dodet, Betty

2016-11-01

Although the presence of an intestinal flora has been known for a long time, the discovery of the role of gut microbiota in human health and disease has been widely recognized as one of the most important advances in the recent years. Chronic diseases may result from dysbiosis, i.e. a disruption of the balance within the bacterial population hosted by the human body. These developments open new prospects in terms of prevention and treatment, including the design of adapted diets, the development of functional foods and fecal transplantation. These discoveries have profoundly altered our view of microbes, of health and disease, of self and non-self, as well as our representations of the body and its relationship with its ecosystem. Gut microbiota is now generally considered as an organ in its own right. A model of the "microbiotic person" thus arises, in which the human organism is defined as an ecosystem, a chimeric superorganism with a double genome, both human and microbial. Thought should be given to the way in which these new paradigms modify lay perceptions of the human body. © 2016 médecine/sciences – Inserm.

Temporal microbiota changes of high-protein diet intake in a rat model.

PubMed

Mu, Chunlong; Yang, Yuxiang; Luo, Zhen; Zhu, Weiyun

2017-10-01

Alterations of specific microbes serve as important indicators that link gut health with specific diet intake. Although a six-week high-protein diet (45% protein) upregulates the pro-inflammatory response and oxidative stress in colon of rats, the dynamic alteration of gut microbiota remains unclear. To dissect temporal changes of microbiota, dynamic analyses of fecal microbiota were conducted using a rat model. Adult rats were fed a normal-protein diet or an HPD for 6 weeks, and feces collected at different weeks were used for microbiota and metabolite analysis. The structural alteration of fecal microbiota was observed after 4 weeks, especially for the decreased appearance of bands related to Akkermansia species. HPD increased numbers of Escherichia coli while decreased Akkermansia muciniphila, Bifidobacterium, Prevotella, Ruminococcus bromii, and Roseburia/Eubacterium rectale (P < 0.05), compared to the normal-protein diet. HPD also decreased the copies of genes encoding butyryl-CoA:acetate CoA-transferase and Prevotella-associated methylmalonyl-CoA decarboxylase α-subunit (P < 0.05). The concentrations of acetate, propionate, and butyrate were decreased by HPD (P < 0.05). Additionally, HPD tended to decrease (P = 0.057) the concentration of IgG in the colonic lumen, which was positively correlated with fecal butyrate at week 6 (P < 0.05). Collectively, this study found the temporal alteration of fecal microbiota related to the decreased numbers and activity of propionate- and butyrate-producing bacteria in feces after the HPD. These findings may provide important reference for linking changes of specific fecal microbes with gut health under high-protein diet. Copyright © 2017 Elsevier Ltd. All rights reserved.

Composition, variability, and temporal stability of the intestinal microbiota of the elderly

PubMed Central

Claesson, Marcus J.; Cusack, Siobhán; O'Sullivan, Orla; Greene-Diniz, Rachel; de Weerd, Heleen; Flannery, Edel; Marchesi, Julian R.; Falush, Daniel; Dinan, Timothy; Fitzgerald, Gerald; Stanton, Catherine; van Sinderen, Douwe; O'Connor, Michael; Harnedy, Norma; O'Connor, Kieran; Henry, Colm; O'Mahony, Denis; Fitzgerald, Anthony P.; Shanahan, Fergus; Twomey, Cillian; Hill, Colin; Ross, R. Paul; O'Toole, Paul W.

2011-01-01

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability. PMID:20571116

The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy

PubMed Central

Whitfield-Cargile, Canaan M.; Cohen, Noah D.; Chapkin, Robert S.; Weeks, Brad R.; Davidson, Laurie A.; Goldsby, Jennifer S.; Hunt, Carrie L.; Steinmeyer, Shelby H.; Menon, Rani; Suchodolski, Jan S.; Jayaraman, Arul; Alaniz, Robert C.

2016-01-01

ABSTRACT Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co-administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota. PMID:27007819

Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge

PubMed Central

Bondia-Pons, Isabel; Maukonen, Johanna; Mattila, Ismo; Rissanen, Aila; Saarela, Maria; Kaprio, Jaakko; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Hyötyläinen, Tuulia; Pietiläinen, Kirsi H.; Orešič, Matej

2014-01-01

Postprandial responses to food are complex, involving both genetic and environmental factors. We studied postprandial responses to a Big Mac meal challenge in monozygotic co-twins highly discordant for body weight. This unique design allows assessment of the contribution of obesity, independent of genetic liability. Comprehensive metabolic profiling using 3 analytical platforms was applied to fasting and postprandial serum samples from 16 healthy monozygotic twin pairs discordant for weight (body mass index difference >3 kg/m2). Nine concordant monozygotic pairs were examined as control pairs. Fecal samples were analyzed to assess diversity of the major bacterial groups by using 5 different validated bacterial group specific denaturing gradient gel electrophoresis methods. No differences in fecal bacterial diversity were detected when comparing co-twins discordant for weight (ANOVA, P<0.05). We found that within-pair similarity is a dominant factor in the metabolic postprandial response, independent of acquired obesity. Branched chain amino acids were increased in heavier as compared with leaner co-twins in the fasting state, but their levels converged postprandially (paired t tests, FDR q<0.05). We also found that specific bacterial groups were associated with postprandial changes of specific metabolites. Our findings underline important roles of genetic and early life factors in the regulation of postprandial metabolite levels.—Bondia-Pons, I., Maukonen, J., Mattila, I., Rissanen, A., Saarela, M., Kaprio, J., Hakkarainen, A., Lundbom, J., Lundbom, N., Hyötyläinen, T., Pietiläinen, K. H., Orešič, M. Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge. PMID:24846387

European consensus conference on faecal microbiota transplantation in clinical practice

PubMed Central

Cammarota, Giovanni; Ianiro, Gianluca; Tilg, Herbert; Rajilić-Stojanović, Mirjana; Kump, Patrizia; Satokari, Reetta; Sokol, Harry; Arkkila, Perttu; Pintus, Cristina; Hart, Ailsa; Segal, Jonathan; Aloi, Marina; Masucci, Luca; Molinaro, Antonio; Scaldaferri, Franco; Gasbarrini, Giovanni; Lopez-Sanroman, Antonio; Link, Alexander; de Groot, Pieter; de Vos, Willem M; Högenauer, Christoph; Malfertheiner, Peter; Mattila, Eero; Milosavljević, Tomica; Nieuwdorp, Max; Sanguinetti, Maurizio; Simren, Magnus; Gasbarrini, Antonio

2017-01-01

Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements. PMID:28087657

Gut microbiota role in irritable bowel syndrome: New therapeutic strategies

PubMed Central

Distrutti, Eleonora; Monaldi, Lorenzo; Ricci, Patrizia; Fiorucci, Stefano

2016-01-01

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required. PMID:26900286

Ecological Restoration of Antibiotic-Disturbed Gastrointestinal Microbiota in Foregut and Hindgut of Cows

PubMed Central

Ji, Shoukun; Jiang, Tao; Yan, Hui; Guo, Chunyan; Liu, Jingjing; Su, Huawei; Alugongo, Gibson M.; Shi, Haitao; Wang, Yajing; Cao, Zhijun; Li, Shengli

2018-01-01

Antibiotically disturbed gastrointestinal microbiota needs a long period time to be restored to normal, which may cause a series of problems to the host. The understanding of restoration of the biased microbiota by antibiotics remains largely unknown. Here, we investigated the microbiota shift in foregut (rumen) and hindgut (rectum) of lactating cows after antibiotics exposure as well as after antibiotics withdrawal with (Microbiota transplantation, MT group) or without (Control, CON group) microbiota transplantation. We were able to demonstrate that microbiota in both foregut and hindgut significantly changed after 3 or 14 days of antibiotics exposure, and the changes persisted over long period of time (>18 days) after withdrawing the antibiotics. We further observed a faster restoration of microbiota in both foregut and hindgut of MT group than CON group, microbiota in foregut was mainly benefited from microbiota transplantation by restoring the alpha-diversity as well as within-group similarity, while microbiota in hindgut was primarily benefited from microbiota transplantation by reestablishing the co-occurrence network (nodes number, edges number, density, modularity as well as closeness centrality). These results together expanded our understanding of restoration of the biased microbiota by antibiotics, and may also be instructive to deal with the delayed microbiota restoration at least in cows. PMID:29594071

Cytotoxicity of Nanoparticles Contained in Food on Intestinal Cells and the Gut Microbiota

PubMed Central

Fröhlich, Esther E.; Fröhlich, Eleonore

2016-01-01

Toxicity of nanoparticles (NPs) upon oral exposure has been studied in animals using physiological changes, behavior, histology, and blood analysis for evaluation. The effects recorded include the combination of the action on cells of the exposed animal and the reaction of the microorganisms that populate the external and internal surfaces of the body. The importance of these microorganisms, collectively termed as microbiota, for the health of the host has been widely recognized. They may also influence toxicity of NPs but these effects are difficult to differentiate from toxicity on cells of the gastrointestinal tract. To estimate the likelihood of preferential damage of the microbiota by NPs the relative sensitivity of enterocytes and bacteria was compared. For this comparison NPs with antimicrobial action present in consumer products were chosen. The comparison of cytotoxicity with Escherichia coli as representative for intestinal bacteria and on gastrointestinal cells revealed that silver NPs damaged bacteria at lower concentrations than enterocytes, while the opposite was true for zinc oxide NPs. These results indicate that silver NPs may cause adverse effects by selectively affecting the gut microbiota. Fecal transplantation from NP-exposed animals to unexposed ones offers the possibility to verify this hypothesis. PMID:27058534

A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies.

PubMed

Rodiño-Janeiro, Bruno K; Vicario, María; Alonso-Cotoner, Carmen; Pascua-García, Roberto; Santos, Javier

2018-03-01

Irritable bowel syndrome (IBS), one of the most frequent digestive disorders, is characterized by chronic and recurrent abdominal pain and altered bowel habit. The origin seems to be multifactorial and is still not well defined for the different subtypes. Genetic, epigenetic and sex-related modifications of the functioning of the nervous and immune-endocrine supersystems and regulation of brain-gut physiology and bile acid production and absorption are certainly involved. Acquired predisposition may act in conjunction with infectious, toxic, dietary and life event-related factors to enhance epithelial permeability and elicit mucosal microinflammation, immune activation and dysbiosis. Notably, strong evidence supports the role of bacterial, viral and parasitic infections in triggering IBS, and targeting microbiota seems promising in view of the positive response to microbiota-related therapies in some patients. However, the lack of highly predictive diagnostic biomarkers and the complexity and heterogeneity of IBS patients make management difficult and unsatisfactory in many cases, reducing patient health-related quality of life and increasing the sanitary burden. This article reviews specific alterations and interventions targeting the gut microbiota in IBS, including prebiotics, probiotics, synbiotics, non-absorbable antibiotics, diets, fecal transplantation and other potential future approaches useful for the diagnosis, prevention and treatment of IBS.

European consensus conference on faecal microbiota transplantation in clinical practice.

PubMed

Cammarota, Giovanni; Ianiro, Gianluca; Tilg, Herbert; Rajilić-Stojanović, Mirjana; Kump, Patrizia; Satokari, Reetta; Sokol, Harry; Arkkila, Perttu; Pintus, Cristina; Hart, Ailsa; Segal, Jonathan; Aloi, Marina; Masucci, Luca; Molinaro, Antonio; Scaldaferri, Franco; Gasbarrini, Giovanni; Lopez-Sanroman, Antonio; Link, Alexander; de Groot, Pieter; de Vos, Willem M; Högenauer, Christoph; Malfertheiner, Peter; Mattila, Eero; Milosavljević, Tomica; Nieuwdorp, Max; Sanguinetti, Maurizio; Simren, Magnus; Gasbarrini, Antonio

2017-04-01

Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements. 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/.

Effect of two seaweed polysaccharides on intestinal microbiota in mice evaluated by illumina PE250 sequencing.

PubMed

Zhang, Zhongshan; Wang, Xiaomei; Han, Shuwen; Liu, Chundong; Liu, Feng

2018-06-01

Effect of polysaccharides from two seaweeds, Porphyra haitanensis and Ulva prolifera, on intestinal microbiota in mice was evaluated by illumina PE250 sequencing. Analysis showed significant structural changes in fecal microbiota among the three sample groups. There were significant differences in the composition of fecal microbiota among the three groups at phylum and genus levels. At the phylum level, the most predominant phylum was Bacteroidetes contributing 58.76%, 73.39%, 75.38% and 64.40% of the fecal microbiota in K, Z, H and D groups respectively, followed by Firmicutes, contributing 37.61%, 23.99%, 21.87% and 30.82% respectively. Many genera were significantly higher in the Z and H group than in the K group, including Prevotellaceae UCG-001 (p<0.05) and Rikenellaceae RC9 (p<0.01). In conclusion, our results suggest that polysaccharide type and glycoside may contribute to shaping mice gut microbiota. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparative effectiveness of faecal microbiota transplant by route of administration.

PubMed

Gundacker, N D; Tamhane, A; Walker, J B; Morrow, C D; Rodriguez, J M

2017-08-01

The optimal route of delivery for faecal microbiota transplant (FMT) is unknown. This observational single-centre study analysed the two-week cure rates for all patients who received FMT from 2013 to 2016 according to route of delivery. Overall, nasogastric delivery of FMT was less effective than lower endoscopic delivery. When patients were stratified by illness severity, nasogastric delivery achieved similar cure rates in healthier individuals, whereas lower endoscopic delivery was preferred for relatively ill individuals. Nasogastric delivery may be less effective than lower endoscopic delivery; however, when taking the cost, preparation and potential risk into account, this difference may not be clinically significant for patients with mild disease. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Phyllosphere Microbiota Composition and Microbial Community Transplantation on Lettuce Plants Grown Indoors

PubMed Central

Williams, Thomas R.

2014-01-01

ABSTRACT The aerial surfaces of plants, or phyllosphere, are microbial habitats important to plant and human health. In order to accurately investigate microbial interactions in the phyllosphere under laboratory conditions, the composition of the phyllosphere microbiota should be representative of the diversity of microorganisms residing on plants in nature. We found that Romaine lettuce grown in the laboratory contained 10- to 100-fold lower numbers of bacteria than age-matched, field-grown lettuce. The bacterial diversity on laboratory-grown plants was also significantly lower and contained relatively higher proportions of Betaproteobacteria as opposed to the Gammaproteobacteria-enriched communities on field lettuce. Incubation of field-grown Romaine lettuce plants in environmental growth chambers for 2 weeks resulted in bacterial cell densities and taxa similar to those on plants in the field but with less diverse bacterial populations overall. In comparison, the inoculation of laboratory-grown Romaine lettuce plants with either freshly collected or cryopreserved microorganisms recovered from field lettuce resulted in the development of a field-like microbiota on the lettuce within 2 days of application. The survival of an inoculated strain of Escherichia coli O157:H7 was unchanged by microbial community transfer; however, the inoculation of E. coli O157:H7 onto those plants resulted in significant shifts in the abundance of certain taxa. This finding was strictly dependent on the presence of a field-associated as opposed to a laboratory-associated microbiota on the plants. Phyllosphere microbiota transplantation in the laboratory will be useful for elucidating microbial interactions on plants that are important to agriculture and microbial food safety. PMID:25118240

Gastrointestinal microbiota in children with autism in Slovakia.

PubMed

Tomova, Aleksandra; Husarova, Veronika; Lakatosova, Silvia; Bakos, Jan; Vlkova, Barbora; Babinska, Katarina; Ostatnikova, Daniela

2015-01-01

Development of Autism Spectrum Disorders (ASD), including autism, is based on a combination of genetic predisposition and environmental factors. Recent data propose the etiopathogenetic role of intestinal microflora in autism. The aim of this study was to elucidate changes in fecal microbiota in children with autism and determine its role in the development of often present gastrointestinal (GI) disorders and possibly other manifestations of autism in Slovakia. The fecal microflora of 10 children with autism, 9 siblings and 10 healthy children was investigated by real-time PCR. The fecal microbiota of autistic children showed a significant decrease of the Bacteroidetes/Firmicutes ratio and elevation of the amount of Lactobacillus spp. Our results also showed a trend in the incidence of elevated Desulfovibrio spp. in children with autism reaffirmed by a very strong association of the amount of Desulfovibrio spp. with the severity of autism in the Autism Diagnostic Interview (ADI) restricted/repetitive behavior subscale score. The participants in our study demonstrated strong positive correlation of autism severity with the severity of GI dysfunction. Probiotic diet supplementation normalized the Bacteroidetes/Firmicutes ratio, Desulfovibrio spp. and the amount of Bifidobacterium spp. in feces of autistic children. We did not find any correlation between plasma levels of oxytocin, testosterone, DHEA-S and fecal microbiota, which would suggest their combined influence on autism development. This pilot study suggests the role of gut microbiota in autism as a part of the "gut-brain" axis and it is a basis for further investigation of the combined effect of microbial, genetic, and hormonal changes for development and clinical manifestation of autism. Copyright © 2014 Elsevier Inc. All rights reserved.

Gut microbiota and obesity.

PubMed

Gérard, Philippe

2016-01-01

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

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12.

PubMed

Uribe-Herranz, Mireia; Bittinger, Kyle; Rafail, Stavros; Guedan, Sonia; Pierini, Stefano; Tanes, Ceylan; Ganetsky, Alex; Morgan, Mark A; Gill, Saar; Tanyi, Janos L; Bushman, Frederic D; June, Carl H; Facciabene, Andrea

2018-02-22

Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12-dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12

PubMed Central

Bittinger, Kyle; Rafail, Stavros; Pierini, Stefano; Tanes, Ceylan; Ganetsky, Alex; Morgan, Mark A.; Gill, Saar; Tanyi, Janos L.; Bushman, Frederic D.; June, Carl H.

2018-01-01

Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12–dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota. PMID:29467322

Dietary polyphenols increase fecal mucin and immunoglobulin A and ameliorate the disturbance in gut microbiota caused by a high fat diet.

PubMed

Taira, Toshio; Yamaguchi, Sayori; Takahashi, Azusa; Okazaki, Yukako; Yamaguchi, Akihiro; Sakaguchi, Hirohide; Chiji, Hideyuki

2015-11-01

The effects of dietary polyphenols on human health have mainly been discussed in the context of preventing degenerative diseases, particularly cardiovascular diseases and cancer. The antioxidant properties of polyphenols have been widely studied, but it has become clear that the mechanism of action of polyphenols extends beyond the modulation of oxidative stress, as they are poorly absorbed from the digestive tract. The purpose of this study was to clarify the effects of polyphenols on the colonic environment, intestinal barrier function, and gut microbiota. We demonstrated that dietary polyphenols derived from aronia, haskap, and bilberry, markedly elevated the amount of fecal mucin and immunoglobulin A (IgA) as an intestinal barrier function and ameliorated the disturbance in gut microbiota caused by a high fat diet in rats. These results suggest that dietary polyphenols play a significant role in the prevention of degenerative diseases through improvement of the colonic environment without any absorption from the digestive tract.

Dietary polyphenols increase fecal mucin and immunoglobulin A and ameliorate the disturbance in gut microbiota caused by a high fat diet

PubMed Central

Taira, Toshio; Yamaguchi, Sayori; Takahashi, Azusa; Okazaki, Yukako; Yamaguchi, Akihiro; Sakaguchi, Hirohide; Chiji, Hideyuki

2015-01-01

The effects of dietary polyphenols on human health have mainly been discussed in the context of preventing degenerative diseases, particularly cardiovascular diseases and cancer. The antioxidant properties of polyphenols have been widely studied, but it has become clear that the mechanism of action of polyphenols extends beyond the modulation of oxidative stress, as they are poorly absorbed from the digestive tract. The purpose of this study was to clarify the effects of polyphenols on the colonic environment, intestinal barrier function, and gut microbiota. We demonstrated that dietary polyphenols derived from aronia, haskap, and bilberry, markedly elevated the amount of fecal mucin and immunoglobulin A (IgA) as an intestinal barrier function and ameliorated the disturbance in gut microbiota caused by a high fat diet in rats. These results suggest that dietary polyphenols play a significant role in the prevention of degenerative diseases through improvement of the colonic environment without any absorption from the digestive tract. PMID:26566306

Disentangling factors that shape the gut microbiota in German Shepherd dogs

PubMed Central

Ramadan, Ziad; Li, Qinghong; Hedhammar, Åke; Reynolds, Arleigh; Spears, Julie; Labuda, Jeff; Pelker, Robyn; Björkstén, Bengt; Dicksved, Johan; Hansson-Hamlin, Helene

2018-01-01

The aim of this study was to explore the development of the gut microbiota in 168 German Shepherd dogs (30 litters) from 7 weeks to 18 months of age and furthermore, to study the effect of relatedness, maternal microbiota composition and living environment in a large and well-defined population of dogs. Using 454 pyrosequencing, we assessed the effects of pre- and postnatal probiotic supplementation (Lactobacillus johnsonii NCC533 (La1)) and analysed whether administration of the probiotic strain influenced fecal microbiota composition in a placebo controlled double-blinded study. The bitches were treated with probiotics or placebo during last trimester of pregnancy and until their puppies were 8 weeks old, the puppies received the same treatment as their mothers between 3–12 weeks of age. Samples from bitches were collected at pregnancy day 42, partum, 4 weeks postpartum and 7 weeks postpartum and from puppies at the age 4 weeks, 7 weeks, 12–13 months and 15–18 months. Serum IgA, total serum IgE, fecal IgA and IgG antibody responses against canine distemper virus were analysed by ELISA in order to detect any immune stimulating effects of the probiotic strain. Analysis of the fecal microbiota composition showed that the predominant phyla were the same in 7 weeks old puppies as in pregnant and lactating bitches (Firmicutes, Fusobacteria, Bacteroidetes). Proportions among different bacteria as well as diversity varied from 7 weeks old puppies up to 15–18 months of age. Litter mates had a more similar fecal microbiota compared to unrelated dogs and 7 weeks old puppies were more similar to their mothers than to unrelated bitches at 7 weeks postpartum but not at partum. We observed a change in the relative abundance of different bacteria during lactation, and an increase in diversity from pregnancy to end of lactation. The microbial diversity was affected by living area where dogs living in big cities had higher diversity compared to dogs living at the

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.

PubMed

Petra, Anastasia I; Panagiotidou, Smaro; Hatziagelaki, Erifili; Stewart, Julia M; Conti, Pio; Theoharides, Theoharis C

2015-05-01

Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Challenges of metabolomics in human gut microbiota research.

PubMed

Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

2016-08-01

The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome

PubMed Central

Chassaing, Benoit; Koren, Omry; Goodrich, Julia; Poole, Angela; Srinivasan, Shanthi; Ley, Ruth E.; Gewirtz, Andrew T.

2015-01-01

Summary The intestinal tract is inhabited by a large diverse community of microbes collectively referred to as gut microbiota. While gut microbiota provide important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease (IBD) and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multilayered mucus structures that cover the intestinal surface thus allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine 1. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro 2, might be promoting the post-mid 20th century increase in IBD 3. Herein, we observed that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in WT hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition, and increased pro-inflammatory potential. Use of germ-free mice and fecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that broad use of

Liver Transplantation and Gut Microbiota Profiling in a Child Colonized by a Multi-Drug Resistant Klebsiella pneumoniae: A New Approach to Move from Antibiotic to "Eubiotic" Control of Microbial Resistance.

PubMed

Del Chierico, Federica; Cardile, Sabrina; Pietrobattista, Andrea; Liccardo, Daniela; Russo, Alessandra; Candusso, Manila; Basso, Maria Sole; Grimaldi, Chiara; Pansani, Laura; Bernaschi, Paola; Torre, Giuliano; Putignani, Lorenza

2018-04-25

The increase of microorganisms multi-drug resistant (MDR) to antibiotics (ATBs) is becoming a global emergency, especially in frail subjects. In chronic liver disease (LD) with indications for liver transplantation (LT), MDR colonization can significantly affect the LT outcome. However, no clear guidelines for microbial management are available. A novel approach toward MDR-colonized patients undergoing LT was developed at our Center refraining from ATBs use during the transplant waiting list, and use of an intensive perioperative prophylaxis cycle. This study aimed to couple clinical evaluation with monitoring of gut microbiota in a pediatric LD patient colonized with MDR Klebsiella pneumoniae (KP) who underwent LT. No peri-transplant complications were reported, and a decontamination from the MDR bacteria occurred during follow-up. Significant changes in gut microbiota, especially during ATB treatment, were reported by microbiota profiling. Patterns of Klebsiella predominance and microbiota diversity revealed opposite temporal trends, with Klebsiella ecological microbiota niches linked to ATB-driven selection. Our infection control program appeared to control complications following LT in an MDR-KP-colonized patient. The perioperative ATB regimen, acting as LT prophylaxis, triggered MDR-KP overgrowth and gut dysbiosis, but buffered infectious processes. Mechanisms modulating the gut ecosystem should be taken into account in MDR colonization clinical management.

Cohabiting family members share microbiota with one another and with their dogs.

PubMed

Song, Se Jin; Lauber, Christian; Costello, Elizabeth K; Lozupone, Catherine A; Humphrey, Gregory; Berg-Lyons, Donna; Caporaso, J Gregory; Knights, Dan; Clemente, Jose C; Nakielny, Sara; Gordon, Jeffrey I; Fierer, Noah; Knight, Rob

2013-04-16

Human-associated microbial communities vary across individuals: possible contributing factors include (genetic) relatedness, diet, and age. However, our surroundings, including individuals with whom we interact, also likely shape our microbial communities. To quantify this microbial exchange, we surveyed fecal, oral, and skin microbiota from 60 families (spousal units with children, dogs, both, or neither). Household members, particularly couples, shared more of their microbiota than individuals from different households, with stronger effects of co-habitation on skin than oral or fecal microbiota. Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more 'skin' microbiota with their own dogs than with other dogs. Although the degree to which these shared microbes have a true niche on the human body, vs transient detection after direct contact, is unknown, these results suggest that direct and frequent contact with our cohabitants may significantly shape the composition of our microbial communities. DOI:http://dx.doi.org/10.7554/eLife.00458.001.

Cohabiting family members share microbiota with one another and with their dogs

PubMed Central

Song, Se Jin; Lauber, Christian; Costello, Elizabeth K; Lozupone, Catherine A; Humphrey, Gregory; Berg-Lyons, Donna; Caporaso, J Gregory; Knights, Dan; Clemente, Jose C; Nakielny, Sara; Gordon, Jeffrey I; Fierer, Noah; Knight, Rob

2013-01-01

Human-associated microbial communities vary across individuals: possible contributing factors include (genetic) relatedness, diet, and age. However, our surroundings, including individuals with whom we interact, also likely shape our microbial communities. To quantify this microbial exchange, we surveyed fecal, oral, and skin microbiota from 60 families (spousal units with children, dogs, both, or neither). Household members, particularly couples, shared more of their microbiota than individuals from different households, with stronger effects of co-habitation on skin than oral or fecal microbiota. Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more ‘skin’ microbiota with their own dogs than with other dogs. Although the degree to which these shared microbes have a true niche on the human body, vs transient detection after direct contact, is unknown, these results suggest that direct and frequent contact with our cohabitants may significantly shape the composition of our microbial communities. DOI: http://dx.doi.org/10.7554/eLife.00458.001 PMID:23599893

Comparison of Sewage and Animal Fecal Microbiomes by using Oligotyping Reveals Potential Human Fecal Indicators in Multiple Taxonomic Groups

EPA Science Inventory

Most DNA-based microbial source tracking (MST) approaches target host-associated organisms within the order Bacteroidales, but human and other animal gut microbiota contain an array of other taxonomic groups that might serve as indicators for sources of fecal pollution. High thr...

Prenatal Androgen Exposure Causes Hypertension and Gut Microbiota Dysbiosis.

PubMed

Sherman, Shermel; Sarsour, Nadeen; Salehi, Marziyeh; Schroering, Allen; Mell, Blair; Joe, Bina; Hill, Jennifer W

2018-02-22

Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in

The Microbiota, the Immune System and the Allograft

PubMed Central

Alegre, Maria-Luisa; Mannon, Roslyn B.; Mannon, Peter J.

2015-01-01

The microbiota represents the complex collections of microbial communities that colonize a host. In health, the microbiota is essential for metabolism, protection against pathogens and maturation of the immune system. In return, the immune system determines the composition of the microbiota. Altered microbial composition (dysbiosis) has been correlated with a number of diseases in humans. The tight reciprocal immune/microbial interactions complicate determining whether dysbiosis is a cause and/or a consequence of immune dysregulation and disease initiation or progression. However, a number of studies in germ-free and antibiotic-treated animal models support causal roles for intestinal bacteria in disease susceptibility. The role of the microbiota in transplant recipients is only starting to be investigated and its study is further complicated by putative contributions of both recipient and donor microbiota. Moreover, both flora may be affected directly or indirectly by immunosuppressive drugs and anti-microbial prophylaxis taken by transplant patients, as well as by inflammatory processes secondary to ischemia/reperfusion and allorecognition, and the underlying cause of end-organ failure. Whether the ensuing dysbiosis affects alloresponses and whether therapies aimed at correcting dysbiosis should be considered in transplant patients constitutes an exciting new field of research. PMID:24840316

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.

PubMed

Shi, Junxiu; Wang, Yifan; He, Jian; Li, Pingping; Jin, Rong; Wang, Ke; Xu, Xi; Hao, Jie; Zhang, Yan; Liu, Hongju; Chen, Xiaoping; Wu, Hounan; Ge, Qing

2017-08-01

Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. © FASEB.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

PubMed

Couturier-Maillard, A; Froux, N; Piotet-Morin, J; Michaudel, C; Brault, L; Le Bérichel, J; Sénéchal, A; Robinet, P; Chenuet, P; Jejou, S; Dumoutier, L; Renauld, J C; Iovanna, J; Huber, S; Quesniaux, Vfj; Sokol, H; Ryffel, B

2018-05-04

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22 -/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

The fecal bacteria

USGS Publications Warehouse

Sadowsky, Michael J.; Whitman, Richard L.

2011-01-01

The Fecal Bacteria offers a balanced, integrated discussion of fecal bacteria and their presence and ecology in the intestinal tract of mammals, in the environment, and in the food supply. This volume covers their use in examining and assessing water quality in order to offer protection from illnesses related to swimming in or ingesting contaminated water, in addition to discussing their use in engineering considerations of water quality, modeling, monitoring, and regulations. Fecal bacteria are additionally used as indicators of contamination of ready-to-eat foods and fresh produce. The intestinal environment, the microbial community structure of the gut microbiota, and the physiology and genomics of this broad group of microorganisms are explored in the book. With contributions from an internationally recognized group of experts, the book integrates medicine, public health, environmental, and microbiological topics in order to provide a unique, holistic understanding of fecal bacteria. Moreover, it shows how the latest basic science and applied research findings are helping to solve problems and develop effective management strategies. For example, readers will discover how the latest tools and molecular approaches have led to our current understanding of fecal bacteria and enabled us to improve human health and water quality. The Fecal Bacteria is recommended for microbiologists, clinicians, animal scientists, engineers, environmental scientists, food safety experts, water quality managers, and students. It will help them better understand fecal bacteria and use their knowledge to protect human and environmental health. They can also apply many of the techniques and molecular tools discussed in this book to the study of a broad range of microorganisms in a variety of habitats.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.

PubMed

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2017-03-01

Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446; http://dx.doi.org/10.1289/EHP360.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice

PubMed Central

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2016-01-01

Background: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. Objectives: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. Methods: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Results: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. Conclusions: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health

Spatial organization of the gastrointestinal microbiota in urban Canada geese

USGS Publications Warehouse

Drovetski, Sergei V.; O'Mahoney, Michael; Ransome, Emma J.; Matterson, Kenan O.; Lim, Haw Chuan; Chesser, Terry; Graves, Gary R.

2018-01-01

Recent reviews identified the reliance on fecal or cloacal samples as a significant limitation hindering our understanding of the avian gastrointestinal (gut) microbiota and its function. We investigated the microbiota of the esophagus, duodenum, cecum, and colon of a wild urban population of Canada goose (Branta canadensis). From a population sample of 30 individuals, we sequenced the V4 region of the 16S SSU rRNA on an Illumina MiSeq and obtained 8,628,751 sequences with a median of 76,529 per sample. These sequences were assigned to 420 bacterial OTUs and a single archaeon. Firmicutes, Proteobacteria, and Bacteroidetes accounted for 90% of all sequences. Microbiotas from the four gut regions differed significantly in their richness, composition, and variability among individuals. Microbial communities of the esophagus were the most distinctive whereas those of the colon were the least distinctive, reflecting the physical downstream mixing of regional microbiotas. The downstream mixing of regional microbiotas was also responsible for the majority of observed co-occurrence patterns among microbial families. Our results indicate that fecal and cloacal samples inadequately represent the complex patterns of richness, composition, and variability of the gut microbiota and obscure patterns of co-occurrence of microbial lineages.

Sex differences in NSAID-induced perturbation of human intestinal barrier function and microbiota.

PubMed

Edogawa, Shoko; Peters, Stephanie A; Jenkins, Gregory D; Gurunathan, Sakteesh V; Sundt, Wendy J; Johnson, Stephen; Lennon, Ryan J; Dyer, Roy B; Camilleri, Michael; Kashyap, Purna C; Farrugia, Gianrico; Chen, Jun; Singh, Ravinder J; Grover, Madhusudan

2018-06-13

Intestinal barrier function and microbiota are integrally related and play critical roles in maintenance of host physiology. Sex is a key biologic variable for several disorders. Our aim was to determine sex-based differences in response to perturbation and subsequent recovery of intestinal barrier function and microbiota in healthy humans. Twenty-three volunteers underwent duodenal biopsies, mucosal impedance, and in vivo permeability measurement. Permeability testing was repeated after administration of indomethacin, then 4 to 6 wk after its discontinuation. Duodenal and fecal microbiota composition was determined using 16S rRNA amplicon sequencing. Healthy women had lower intestinal permeability and higher duodenal and fecal microbial diversity than healthy men. Intestinal permeability increases after indomethacin administration in both sexes. However, only women demonstrated decreased fecal microbial diversity, including an increase in Prevotella abundance, after indomethacin administration. Duodenal microbiota composition did not show sex-specific changes. The increase in permeability and microbiota changes normalized after discontinuation of indomethacin. In summary, women have lower intestinal permeability and higher microbial diversity. Intestinal permeability is sensitive to perturbation but recovers to baseline. Gut microbiota in women is sensitive to perturbation but appears to be more stable in men. Sex-based differences in intestinal barrier function and microbiome should be considered in future studies.-Edogawa, S., Peters, S. A., Jenkins, G. D., Gurunathan, S. V., Sundt, W. J., Johnson, S., Lennon, R. J., Dyer, R. B., Camilleri, M., Kashyap, P. C., Farrugia, G., Chen, J., Singh, R. J., Grover, M. Sex differences in NSAID-induced perturbation of human intestinal barrier function and microbiota.

Moisture content during extrusion of oats impacts the initial fermentation metabolites and probiotic bacteria during extended fermentation by human fecal microbiota.

PubMed

Brahma, Sandrayee; Weier, Steven A; Rose, Devin J

2017-07-01

Extrusion exposes flour components to high pressure and shear during processing, which may affect the dietary fiber fermentability by human fecal microbiota. The objective of this study was to determine the effect of flour moisture content during extrusion on in vitro fermentation properties of whole grain oats. Extrudates were processed at three moisture levels (15%, 18%, and 21%) at fixed screw speed (300rpm) and temperature (130°C). The extrudates were then subjected to in vitro digestion and fermentation. Extrusion moisture significantly affected water-extractable β-glucan (WE-BG) in the extrudates, with samples processed at 15% moisture (lowest) and 21% moisture (highest) having the highest concentration of WE-BG. After the first 8h of fermentation, more WE-BG remained in fermentation media in samples processed at 15% moisture compared with the other conditions. Also, extrusion moisture significantly affected the production of acetate, butyrate, and total SCFA by the microbiota during the first 8h of fermentation. Microbiota grown on extrudates processed at 18% moisture had the highest production of acetate and total SCFA, whereas bacteria grown on extrudates processed at 15% and 18% moisture had the highest butyrate production. After 24h of fermentation, samples processed at 15% moisture supported lower Bifidobacterium counts than those produced at other conditions, but had among the highest Lactobacillus counts. Thus, moisture content during extrusion significantly affects production of fermentation metabolites by the gut microbiota during the initial stages of fermentation, while also affecting probiotic bacteria counts during extended fermentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acclimation and Institutionalization of the Mouse Microbiota Following Transportation

PubMed Central

Montonye, Dan R.; Ericsson, Aaron C.; Busi, Susheel B.; Lutz, Cathleen; Wardwell, Keegan; Franklin, Craig L.

2018-01-01

Using animal models, the gut microbiota has been shown to play a critical role in the health and disease of many organ systems. Unfortunately, animal model studies often lack reproducibility when performed at different institutions. Previous studies in our laboratory have shown that the gut microbiota of mice can vary with a number of husbandry factors leading us to speculate that differing environments may alter gut microbiota, which in turn may influence animal model phenotypes. As an extension of these studies, we hypothesized that the shipping of mice from a mouse producer to an institution will result in changes in the type, relative abundance, and functional composition of the gut microbiota. Furthermore, we hypothesized that mice will develop a microbiota unique to the institution and facility in which they are housed. To test these hypotheses, mice of two strains (C57BL/6J and BALB/cJ), two age groups (4 week and 8 week old), and originating from two types of housing (research animal facility under conventional housing and production facilities under maximum barrier housing) were obtained from The Jackson Laboratory. Fecal samples were collected the day prior to shipping, immediately upon arrival, and then on days 2, 5, 7, and weeks 2, 4, and 9 post-arrival. Following the first post-arrival fecal collection, mice were separated into 2 groups and housed at different facilities at our institution while keeping their caging, diet, and husbandry practices the same. DNA was extracted from the collected fecal pellets and 16S rRNA amplicons were sequenced in order to characterize the type and relative abundance of gut bacteria. Principal component analysis (PCA) and permutational multivariate analysis of variance (PERMANOVA) demonstrated that both the shipping and the institution and facility in which mice were housed altered the gut microbiota. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) predicted differences in

Acclimation and Institutionalization of the Mouse Microbiota Following Transportation.

PubMed

Montonye, Dan R; Ericsson, Aaron C; Busi, Susheel B; Lutz, Cathleen; Wardwell, Keegan; Franklin, Craig L

2018-01-01

Using animal models, the gut microbiota has been shown to play a critical role in the health and disease of many organ systems. Unfortunately, animal model studies often lack reproducibility when performed at different institutions. Previous studies in our laboratory have shown that the gut microbiota of mice can vary with a number of husbandry factors leading us to speculate that differing environments may alter gut microbiota, which in turn may influence animal model phenotypes. As an extension of these studies, we hypothesized that the shipping of mice from a mouse producer to an institution will result in changes in the type, relative abundance, and functional composition of the gut microbiota. Furthermore, we hypothesized that mice will develop a microbiota unique to the institution and facility in which they are housed. To test these hypotheses, mice of two strains (C57BL/6J and BALB/cJ), two age groups (4 week and 8 week old), and originating from two types of housing (research animal facility under conventional housing and production facilities under maximum barrier housing) were obtained from The Jackson Laboratory. Fecal samples were collected the day prior to shipping, immediately upon arrival, and then on days 2, 5, 7, and weeks 2, 4, and 9 post-arrival. Following the first post-arrival fecal collection, mice were separated into 2 groups and housed at different facilities at our institution while keeping their caging, diet, and husbandry practices the same. DNA was extracted from the collected fecal pellets and 16S rRNA amplicons were sequenced in order to characterize the type and relative abundance of gut bacteria. Principal component analysis (PCA) and permutational multivariate analysis of variance (PERMANOVA) demonstrated that both the shipping and the institution and facility in which mice were housed altered the gut microbiota. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) predicted differences in

Differential decomposition of bacterial and viral fecal indicators in common human pollution types.

PubMed

Wanjugi, Pauline; Sivaganesan, Mano; Korajkic, Asja; Kelty, Catherine A; McMinn, Brian; Ulrich, Robert; Harwood, Valerie J; Shanks, Orin C

2016-11-15

Understanding the decomposition of microorganisms associated with different human fecal pollution types is necessary for proper implementation of many water quality management practices, as well as predicting associated public health risks. Here, the decomposition of select cultivated and molecular indicators of fecal pollution originating from fresh human feces, septage, and primary effluent sewage in a subtropical marine environment was assessed over a six day period with an emphasis on the influence of ambient sunlight and indigenous microbiota. Ambient water mixed with each fecal pollution type was placed in dialysis bags and incubated in situ in a submersible aquatic mesocosm. Genetic and cultivated fecal indicators including fecal indicator bacteria (enterococci, E. coli, and Bacteroidales), coliphage (somatic and F+), Bacteroides fragilis phage (GB-124), and human-associated genetic indicators (HF183/BacR287 and HumM2) were measured in each sample. Simple linear regression assessing treatment trends in each pollution type over time showed significant decay (p ≤ 0.05) in most treatments for feces and sewage (27/28 and 32/40, respectively), compared to septage (6/26). A two-way analysis of variance of log 10 reduction values for sewage and feces experiments indicated that treatments differentially impact survival of cultivated bacteria, cultivated phage, and genetic indicators. Findings suggest that sunlight is critical for phage decay, and indigenous microbiota play a lesser role. For bacterial cultivated and genetic indicators, the influence of indigenous microbiota varied by pollution type. This study offers new insights on the decomposition of common human fecal pollution types in a subtropical marine environment with important implications for water quality management applications. Published by Elsevier Ltd.

Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.

PubMed

Peled, Jonathan U; Devlin, Sean M; Staffas, Anna; Lumish, Melissa; Khanin, Raya; Littmann, Eric R; Ling, Lilan; Kosuri, Satyajit; Maloy, Molly; Slingerland, John B; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Shono, Yusuke; Slingerland, Ann E; Docampo, Melissa D; Sung, Anthony D; Weber, Daniela; Alousi, Amin M; Gyurkocza, Boglarka; Ponce, Doris M; Barker, Juliet N; Perales, Miguel-Angel; Giralt, Sergio A; Taur, Ying; Pamer, Eric G; Jenq, Robert R; van den Brink, Marcel R M

2017-05-20

Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

The evolution of the gut microbiota in the giant and the red pandas.

PubMed

Li, Ying; Guo, Wei; Han, Shushu; Kong, Fanli; Wang, Chengdong; Li, Desheng; Zhang, Heming; Yang, Mingyao; Xu, Huailiang; Zeng, Bo; Zhao, Jiangchao

2015-05-18

The independent dietary shift from carnivore to herbivore with over 90% being bamboo in the giant and the red pandas is of great interests to biologists. Although previous studies have shown convergent evolution of the giant and the red pandas at both morphological and molecular level, the evolution of the gut microbiota in these pandas remains largely unknown. The goal of this study was to determine whether the gut microbiota of the pandas converged due to the same diet, or diverged. We characterized the fecal microbiota from these two species by pyrosequencing the 16S V1-V3 hypervariable regions using the 454 GS FLX Titanium platform. We also included fecal samples from Asian black bears, a species phylogenetically closer to the giant panda, in our analyses. By analyzing the microbiota from these 3 species and those from other carnivores reported previously, we found the gut microbiotas of the giant pandas are distinct from those of the red pandas and clustered closer to those of the black bears. Our data suggests the divergent evolution of the gut microbiota in the pandas.

Molecular assessment of the fecal microbiota in healthy cats and dogs before and during supplementation with fructo-oligosaccharides (FOS) and inulin using high-throughput 454-pyrosequencing

PubMed Central

Barcenas-Walls, Jose R.; Suchodolski, Jan S.; Steiner, Jörg M.

2017-01-01

Prebiotics are selectively fermentable dietary compounds that result in changes in the composition and/or activity of the intestinal microbiota, thus conferring benefits upon host health. In veterinary medicine, commercially available products containing prebiotics have not been well studied with regard to the changes they trigger on the composition of the gut microbiota. This study evaluated the effect of a commercially available nutraceutical containing fructo-oligosaccharides (FOS) and inulin on the fecal microbiota of healthy cats and dogs when administered for 16 days. Fecal samples were collected at two time points before and at two time points during prebiotic administration. Total genomic DNA was obtained from fecal samples and 454-pyrosequencing was used for 16S rRNA gene bacterial profiling. The linear discriminant analysis (LDA) effect size (LEfSe) method was used for detecting bacterial taxa that may respond (i.e., increase or decrease in its relative abundance) to prebiotic administration. Prebiotic administration was associated with a good acceptance and no side effects (e.g., diarrhea) were reported by the owners. A low dose of prebiotics (50 mL total regardless of body weight with the end product containing 0.45% of prebiotics) revealed a lower abundance of Gammaproteobacteria and a higher abundance of Veillonellaceae during prebiotic administration in cats, while Staphylococcaceae showed a higher abundance during prebiotic administration in dogs. These differences were not sufficient to separate bacterial communities as shown by analysis of weighted UniFrac distance metrics. A predictive approach of the fecal bacterial metagenome using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) also did not reveal differences between the period before and during prebiotic administration. A second trial using a higher dose of prebiotics (3.2 mL/kg body weight with the end product containing 3.1% of prebiotics) was

Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility.

PubMed

Yang, Mo; Fukui, Hirokazu; Eda, Hirotsugu; Xu, Xin; Kitayama, Yoshitaka; Hara, Ken; Kodani, Mio; Tomita, Toshihiko; Oshima, Tadayuki; Watari, Jiro; Miwa, Hiroto

2017-04-01

The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract. NEW & NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in

Evaluation of stool microbiota signatures in two cohorts of Asian (Singapore and Indonesia) newborns at risk of atopy

PubMed Central

2011-01-01

Background Studies have suggested that demographic and lifestyle factors could shape the composition of fecal microbiota in early life. This study evaluated infant stool microbiota signatures in two Asian populations, Singapore (n = 42) and Indonesia (n = 32) with contrasting socioeconomic development, and examined the putative influences of demographic factors on these human fecal associated bacterial signatures. Results Longitudinal analysis showed associations of geographical origin with Clostridium leptum, Atopobium and Bifidobacterium groups. Mode of delivery had the largest effect on stool microbiota signatures influencing the abundance of four bacterial groups. Significantly higher abundance of bacterial members belonging to the Bacteroides-Prevotella, Bifidobacterium and Atopobium groups, but lower abundance of Lactobacilli-Enterococci group members, were observed in vaginal delivered compared to caesarean delivered infants. Demographic factors influencing the structure of infants stool microbiota during the first year of life included breastfeeding, age of weaning, sibship size and exposure to antibiotics. Conclusions Differences in stool microbiota signatures were observed in relation to various demographic factors. These features may confound studies relating to the association of the structure of fecal microbiota and the predisposition to human modern disease. PMID:21875444

Microbiota-activated CD103+ DCs stemming from microbiota adaptation specifically drive γδT17 proliferation and activation.

PubMed

Fleming, Chris; Cai, Yihua; Sun, Xuan; Jala, Venkatakrishna R; Xue, Feng; Morrissey, Samantha; Wei, Yu-Ling; Chien, Yueh-Hsiu; Zhang, Huang-Ge; Haribabu, Bodduluri; Huang, Jian; Yan, Jun

2017-04-24

IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103 + dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103 + DCs, and γδT17 cells. Immunophenotyping of IL-17r -/- mice and IL-17r -/- IRF8 -/- mice were performed by ex vivo immunostaining and flow cytometric analysis. We observed striking microbiome differences in the oral cavity and gut of IL-17r -/- mice by sequencing 16S rRNA gene (v1-v3 region) and analyzed using QIIME 1.9.0 software platform. Principal coordinate analysis of unweighted UniFrac distance matrix showed differential clustering for WT and IL-17r -/- mice. We found drastic homeostatic expansion of γδT17 in all major tissues, most prominently in cervical lymph nodes (cLNs) with monoclonal expansion of Vγ6 γδT17 in IL-17r -/- mice. Ki-67 staining and in vitro CFSE assays showed cellular proliferation due to cell-to-cell contact stimulation with microbiota-activated CD103 + DCs. A newly developed double knockout mice model for IL-17r and CD103 + DCs (IL-17r -/- IRF8 -/- ) showed a specific reduction in Vγ6 γδT17. Vγ6 γδT17 expansion is inhibited in germ-free mice and antibiotic-treated specific pathogen-free (SPF) mice. Microbiota transfer using cohousing of IL-17r -/- mice with wildtype mice induces γδT17 expansion in the wildtype mice with increased activated CD103 + DCs in cLNs. However, microbiota transfer using fecal transplant through oral gavage to bypass the oral cavity showed no difference in colon or systemic γδT17 expansion. These findings reveal for the first time that γδT17 cells are regulated by microbiota dysbiosis through cell-to-cell contact with activated CD103 + DCs leading to drastic systemic, monoclonal

Association between Yogurt Consumption and Intestinal Microbiota in Healthy Young Adults Differs by Host Gender

PubMed Central

Suzuki, Yoshio; Ikeda, Keiichi; Sakuma, Kazuhiko; Kawai, Sachio; Sawaki, Keisuke; Asahara, Takashi; Takahashi, Takuya; Tsuji, Hirokazu; Nomoto, Koji; Nagpal, Ravinder; Wang, Chongxin; Nagata, Satoru; Yamashiro, Yuichiro

2017-01-01

Human intestinal microbiota are influenced by various factors viz. diet, environment, age, gender, geographical, and socioeconomic situation, etc. among which diet has the most profound impact. However, studies investigating this impact have mostly included subjects from diverse geographic/socioeconomic backgrounds and hence the precise effects of dietary factors on gut microbiota composition remain largely confounded. Herein, with an aim to evaluate the association between dietary habits, specifically yogurt consumption, and the gut microbiota in healthy young adults sharing similar age, lifestyle routine, geographical setting, etc., we conducted a cross-sectional study wherein 293 collegiate freshmen answered a questionnaire about their frequency of yogurt consumption over the last 2 months and provided stool specimens for microbiota analysis. Fecal microbiota were analyzed by highly sensitive reverse-transcription-quantitative-PCR assays targeting bacterial 16S rRNA molecules. Fecal organic acids were measured by HPLC. Overall, the gut microbiota were predominated (97.1 ± 8.6%) by Clostridium coccoides group, Clostridium leptum subgroup, Bacteroides fragilis group, Bifidobacterium and Atopobium cluster. Interestingly, after adjusting the data for yogurt consumption, females were found to have higher total bacterial (P = 0.013) and Bifidobacterium (P = 0.046) count and fecal pH (P = 0.007) and lower fecal concentration of total organic acids (P = 0.030), succinic acid (P = 0.007) and formic acid (P = 0.046) as compared to males. Altogether, yogurt consumption showed positive linear association with Lactobacillus and Lactobacillus gasseri subgroup in both male and female subjects; however, several gender-specific disparities were also detected in this yogurt-microbiota association. Yogurt consumption demonstrated a negative association with L. sakei subgroup, Enterobacteriaceae and Staphylococcus in males but shared a positive association with L. casei subgroup

Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children

PubMed Central

Subramanian, Sathish; Huq, Sayeeda; Yatsunenko, Tanya; Haque, Rashidul; Mahfuz, Mustafa; Alam, Mohammed A.; Benezra, Amber; DeStefano, Joseph; Meier, Martin F.; Muegge, Brian D.; Barratt, Michael J.; VanArendonk, Laura G.; Zhang, Qunyuan; Province, Michael A.; Petri, William A.; Ahmed, Tahmeed; Gordon, Jeffrey I.

2014-01-01

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children, living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare development (defined here as maturation) of a child’s fecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors including diarrhea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes. PMID

Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage?

PubMed

Davido, B; Batista, R; Michelon, H; Lepainteur, M; Bouchand, F; Lepeule, R; Salomon, J; Vittecoq, D; Duran, C; Escaut, L; Sobhani, I; Paul, M; Lawrence, C; Perronne, C; Chast, F; Dinh, A

2017-04-01

Carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) carriage present a major public health challenge. Decolonization strategies are lacking. We aimed to evaluate the impact of faecal microbiota transplantation (FMT) on a cohort of patients with digestive tract colonization by CRE or VRE. Eight patients were included: six carrying CRE and two colonized by VRE. One month after FMT, two patients were free from CRE carriage, and another patient was free from VRE after three months. In our experience, this strategy is safe. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.