Fecal Microbial Transplantation Research Articles

The success of fecal microbial transplantation in Clostridium difficile infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study

ABSTRACT Background Fecal microbial transplantation (FMT) is used in the treatment of relapsing Clostridium difficile infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success. Results Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of Klebsiella and Escherichia. A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage α-diversity and lower relative abundance compared to the donors of a failed initial FMT. Conclusions In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.

Host NLRP6 exacerbates graft-versus-host disease independent of gut microbial composition.

Host NOD-like receptor family pyrin domain-containing 6 (NLRP6) regulates innate immune responses and gastrointestinal homeostasis. Its protective role in intestinal colitis and tumorigenesis is dependent on the host microbiome. Host innate immunity and microbial diversity also play a role in the severity of allogeneic immune-mediated gastrointestinal graft-versus-host disease (GVHD), the principal toxicity after allogeneic haematopoietic cell transplantation. Here, we examined the role of host NLRP6 in multiple murine models of allogeneic bone marrow transplantation. In contrast to its role in intestinal colitis, host NLRP6 aggravated gastrointestinal GVHD. The impact of host NLRP6 deficiency in mitigating GVHD was observed regardless of co-housing, antibiotic treatment or colonizing littermate germ-free wild-type and NLRP6-deficient hosts with faecal microbial transplantation from specific pathogen-free wild-type and Nlrp6-/- animals. Chimaera studies were performed to assess the role of NLRP6 expression on host haematopoietic and non-haematopoietic cells. The allogeneic [B6Ly5.2 → Nlrp6-/-] animals demonstrated significantly improved survival compared to the allogeneic [B6Ly5.2 → B6] animals, but did not alter the therapeutic graft-versus-tumour effects after haematopoietic cell transplantation. Our results unveil an unexpected, pathogenic role for host NLRP6 in gastrointestinal GVHD that is independent of variations in the intestinal microbiome and in contrast to its well-appreciated microbiome-dependent protective role in intestinal colitis and tumorigenesis.

Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity.

The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.

Generation and robustness of Boolean networks to model Clostridium difficile infection

One of the more common healthcare associated infection is Chronic diarrhea. This disease is caused by the bacterium Clostridium difficile which alters the normal composition of the human gut flora. The most successful therapy against this infection is the fecal microbial transplant (FMT). They displace C. difficile and contribute to gut microbiome resilience, stability and prevent further episodes of diarrhea. The microorganisms in the FMT their interactions and inner dynamics reshape the gut microbiome to a healthy state. Even though microbial interactions play a key role in the development of the disease, currently, little is known about their dynamics and properties. In this context, a Boolean network model for C. difficile infection (CDI) describing one set of possible interactions was recently presented. To further explore the space of possible microbial interactions, we propose the construction of a neutral space conformed by a set of models that differ in their interactions, but share the final community states of the gut microbiome under antibiotic perturbation and CDI. To begin with the analysis, we use the previously described Boolean network model and we demonstrate that this model is in fact a threshold Boolean network (TBN). Once the TBN model is set, we generate and use an evolutionary algorithm to explore to identify alternative TBNs. We organize the resulting TBNs into clusters that share similar dynamic behaviors. For each cluster, the associated neutral graph is constructed and the most relevant interactions are identified. Finally, we discuss how these interactions can either affect or prevent CDI.

Abstract B063: Leveraging gut microbiota networks to impact tumor immunotherapy

Abstract The human gut microbiota forms a diverse, dynamic and complex ecosystem that modulates numerous host processes including metabolism, inflammation and cellular and humoral immune responses. Emerging data suggest that the gut microbiota of cancer patients may predict tumor response to immune checkpoint inhibitors (ICI). To better understand how the microbiome may impact response to ICI, we have developed and validated robust tumor models using either conventional mice treated with antibiotics or germ-free (GF) mice. We have confirmed in both models, that mice lacking a diverse microbiome fail to mount an efficient antitumor immune response after treatment with anti-PD-1, primarily due to T-cell dysfunction. This response to anti-PD-1 can be restored by introduction of a microbiome using fecal microbial transplant (FMT) prepared from stool from healthy donors in GF mice, and is driven by increased tumor-infiltrating lymphocytes (TILs), specifically CD8+ T-cells. Importantly, for the first time, we show that the bacterial spore fraction from healthy donor stool can also restore response to anti-PD-1 and increase CD8+ TILs in both conventional mice treated with antibiotics and GF mice. We have also tested cancer patient-derived microbiome samples that are efficacious or non-efficacious in GF mouse models. We have sequenced the input material as well as the engrafted gut microbiota in these mice via 16S rDNA sequencing. Comparison of these sequences has enabled us to develop a “microbiome signature” of response that is being used in the development of a microbiome based therapy for combination with ICI. Based on these encouraging animal model data we plan to initiate a randomized, placebo-controlled clinical study at MD Anderson Cancer Center in 2018, sponsored by the Parker Institute for Cancer Immunotherapy, in patients with advanced metastatic melanoma. The clinical trial will evaluate the impact of an anti-PD-1 checkpoint inhibitor with adjunctive microbiome therapy on patient outcomes. Seres is developing SER-401, a preclinical stage oral microbiome therapy to improve the efficacy and safety of immunotherapy. Our drug discovery strategy combines computational analyses and empirical in vitro, in vivo and ex-vivo screening of strains and consortia to inform selection and drive microbiome drug design. Data from such a comprehensive approach are invaluable for designing compositions of bacteria that form “functional ecological networks” that can impact response to ICI therapy. We believe these data will provide insight into how microbiome drugs can be developed in the setting of immunotherapy to augment the efficacy of ICIs by altering the cancer-immune set point. Citation Format: Lata Jayaraman, Jaclyn Sceneay, Srimathi Srinivasan, Keith Halley, Meghna Bist, Kathleen Cieciuch, George Marnellos, Christopher Desjardins, Jennifer Wortman, Matthew Henn, David Cook. Leveraging gut microbiota networks to impact tumor immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B063.

The Gut Microbiome as a Target for IBD Treatment: Are We There Yet?

This review aims to highlight recent research on the gut microbiome in IBD and the application of microbiome-modulating therapies for the treatment of IBD including the use of the microbiome as an indicator for disease severity and treatment response. Despite the high number of gut microbiome studies and emerging evidence supporting the gut microbiome's involvement in disease pathogenesis, no single microorganism has been identified as a pathogenic agent in IBD. Retrospective studies and meta-analyses on antibiotic use in ulcerative colitis and Crohn's disease and long-term outcomes are conflicting. Similarly, the use of probiotics for the treatment of IBD remains inconclusive; however, some encouraging results are emerging as microbial concoctions are optimized to include beneficial bacterial strains. Fecal microbial transplantation (FMT) is currently emerging as one of the more promising microbiome-modulating IBD therapies. FMT studies in ulcerative colitis have shown improved remission rates compared to placebo; however, relatively small study sample sizes and varied treatment methods, limit definitive conclusions. With clear evidence of an IBD gut dysbiosis, novel therapies to treat and prevent disease relapse will undoubtedly require a microbiome-modulating approach. The complexity and variability of IBD disease pathogenesis (disease phenotype, gut microbiome, host genetic susceptibility, and environmental factors) will likely require a personalized and multidimensional treatment approach where microbiome-modulating therapy is coupled with other therapies to target other IBD disease components.

Alcohol, liver disease and the gut microbiota.

Alcoholic liver disease, which ranges from mild disease to alcoholic hepatitis and cirrhosis, is a leading cause of morbidity and mortality worldwide. Alcohol intake can lead to changes in gut microbiota composition, even before liver disease development. These alterations worsen with advancing disease and could be complicit in disease progression. Microbial function, especially related to bile acid metabolism, can modulate alcohol-associated injury even in the presence of cirrhosis and alcoholic hepatitis. Microbiota changes might also alter brain function, and the gut-brain axis might be a potential target to reduce alcoholic relapse risk. Gut microbiota manipulation including probiotics, faecal microbial transplant and antibiotics has been studied in alcoholic liver disease with varying success. Further investigation of the modulation of the gut-liver axis is relevant, as most of these patients are not candidates for liver transplantation. This Review focuses on clinical studies involving the gut microbiota in patients with alcoholic liver disease across the spectrum from alcoholic fatty liver to cirrhosis and alcoholic hepatitis. Specific alterations in the gut-liver-brain axis that are complicit in the interactions between the gut microbiota and alcohol addiction are also reviewed.

Modulation of autoimmune arthritis by environmental ‘hygiene’ and commensal microbiota

Observations in patients with autoimmune diseases and studies in animal models of autoimmunity have revealed that external environmental factors including exposure to microbes and the state of the host gut microbiota can influence susceptibility to autoimmunity and subsequent disease development. Mechanisms underlying these outcomes continue to be elucidated. These include deviation of the cytokine response and imbalance between pathogenic versus regulatory T cell subsets. Furthermore, specific commensal organisms are associated with enhanced severity of arthritis in susceptible individuals, while exposure to certain microbes or helminths can afford protection against this disease. In addition, the role of metabolites (e.g., short-chain fatty acids, tryptophan catabolites), produced either by the microbes themselves or from their action on dietary products, in modulation of arthritis is increasingly being realized. In this context, re-setting of the microbial dysbiosis in RA using prebiotics, probiotics, or fecal microbial transplant is emerging as a promising approach for the prevention and treatment of arthritis. It is hoped that advances in defining the interplay between gut microbiota, dietary products, and bioactive metabolites would help in the development of therapeutic regimen customized for the needs of individual patients in the near future.

Multiple sclerosis and faecal microbiome transplantation: are you going to eat that?

Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.

Recent Advances in Probiotics as Live Biotherapeutics Against Gastrointestinal Diseases.

Gastrointestinal (GI) diseases are a major cause of emergency department visits requiring hospitalizations leading to considerable burden on global economy. Several factors contribute to the onset of gastrointestinal diseases such as pathogens (parasites, bacteria, virus, toxins etc.), autoimmune disorders and severe inflammation of intestine. One common feature among all these diseases is the dysentery and alteration of gut microbiota composition (gut dysbiosis). Apart from conventional therapies such as antibiotics and ORS supplementation, gut microbiota modulation with probiotic supplementation has emerged as a successful and healthy alternative in mitigating GI diseases. In this review our goal is to discuss the causes of gastrointestinal diseases and the present state of various therapeutic strategies such as probiotics as live biotherapeutics and Fecal Microbial Transplants (FMT's). Several reports and clinical trials point out to the beneficial effects of probiotics in modulating the gut microbiota and improving the side effects of gastrointestinal diseases. Live biotherapeutics and FMT's could be suitable and successful alternatives to conventional therapies in mitigating the gastrointestinal pathogens.

Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation

BackgroundFaecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied.ResultsWe studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12 months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns.ConclusionsThe impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.

Defining cooperative roles for colonic microbiota and Muc2 mucin in mediating innate host defense against Entamoeba histolytica.

Amebiasis is caused by the protozoan parasite Entamoeba histolytica (Eh), a potentially fatal disease occurring mainly in developing countries. How Eh interacts with innate host factors in the gut is poorly understood. Eh resides and feed in/on the outer colonic mucus layer and thus share an ecological niche with indigenous microbiota. As gut microbiota regulates innate immune responses, in this study we characterized the cooperative roles that microbiota and the mucus layer play in Eh-induced pro-inflammatory responses in the colon. To study this, we used antibiotics treated and non-treated specific pathogen free Muc2-/- and Muc2+/+ littermates and germ-free mice inoculated with Eh in colonic loops as a short infection model. In antibiotic treated Muc2-/- and Muc2+/+ littermates, Eh elicited robust mucus and water secretions, enhanced pro-inflammatory cytokines and chemokine expression with elevated MPO activity and higher pathology scores as compared to the modest response observed in non-antibiotic treated littermates. Host responses were microbiota specific as mucus secretion and pro-inflammatory responses were attenuated following homologous fecal microbial transplants in antibiotic-treated Muc2+/+ quantified by secretion of 3H-glucosamine newly synthesized mucin, Muc2 mucin immunostaining and immunohistochemistry. Eh-elicited pro-inflammatory responses and suppressed goblet cell transcription factor Math1 as revealed by in vivo imaging of Eh-colonic loops in Math1GFP mice, and in vitro using Eh-stimulated LS174T human colonic goblet cells. Eh in colonic loops increased bacterial translocation of bioluminescent E. coli and indigenous bacteria quantified by FISH and quantitative PCR. In germ-free animals, Eh-induced mucus/water secretory responses, but acute pro-inflammatory responses and MPO activity were severely impaired, allowing the parasite to bind to and disrupt mucosal epithelial cells. These findings have identified key roles for intestinal microbiota and mucus in regulating innate host defenses against Eh, and implicate dysbiosis as a risk factor for amebiasis that leads to exacerbated immune responses to cause life-threatening disease.

615. Can We Restore the Lung Microbiome with Fecal Microbiota Transplant (FMT)?

BackgroundUnabated use of antibiotics for human diseases, in livestock and aquaculture has resulted in natural selection of multi-drug-resistant organisms (MDROs). The emergence of pan-resistant strains of Pseudomonas spp. pose a major threat to patients appropriately exposed to antibiotics (e.g., cystic fibrosis, lung transplant recipients). This organism evades antibiotics by a combination of efflux pumps, harboring multiple-resistant genes and acquiring low permeability of the outer membrane. Altering the gut microbiome could potentially modify the lung microbiome of patients colonized or infected with MDROs.MethodsA 17-year-old patient with CF developed recurrent exacerbations with an extreme drug-resistant Pseudomonas aeruginosa; due to the lack of effective antibiotics to treat her while awaiting a decision to proceed with lung transplantation, sputum cultures were collected as part of clinical care. We modeled patient-derived isolate of predominantly MDR Pseudomonas in C57Bl6/j mice, where we engrafted the isolate into humanized murine lungs and studied host cytokine responses and microbial composition of the gut and lungs to the engraftment.ResultsOur data shows that there is a dominant IL6- and IL17-mediated immune response to the engraftment, accompanied by measurable changes to the lung and gut microbiota. We also show that some of these changes can be reversed by fecal microbial transplant (FMT) of ‘normal’ microbiota into the gut and lungs.ConclusionThis murine model results suggest a potential role and effectiveness of gut FMT as a therapeutic measure for MDR bacterial infection in the lungs. Further studies are required to assess response in humans.Disclosures L. M. Abbo, Roche Diagnostics: Scientific Advisor, Consulting fee.

Reverse phenotype transfer via fecal microbial transplantation in inflammatory bowel disease

Inflammatory bowel disease (IBD) is characterized by a disbalance in the composition of intestinal microbiota. It is not clear whether such dysbiosis is a cause or a consequence of a disease state. Fecal microbiota transplantation (FMT) from a healthy donor to a patient or diseased animal is a valuable tool for targeted modification of microbiome leading to therapeutic response. Positive effect has been shown in therapy of a number of gastrointestinal as well as non-gastrointestinal diseases. In addition, FMT has been successfully used to transfer the diseased phenotype form a donor with the disease to a healthy recipient. However, targeted modification of the microbiome before the onset of colitis has not been shown previously. Based on our preliminary results, we propose the hypothesis of so called reverse phenotype transfer in IBD. This term describes the phenomenon, in which the transplantation of gut microbiota from a donor more sensitive to IBD to a healthy recipient leads to resistance of the recipient to IBD and vice versa. Mice that received FMT from donors with severe colitis have shown improved colitis score compared with mice that received FMT from donors more resistant to development of colitis. Such reverse phenotype transfer has broad implications, especially in terms of preventive medicine. However, detailed mechanisms need to be elucidated to conclude the validity of the phenomenon.

The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility.

Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's patches and elsewhere, which together have profound effects on local and systemic inflammation. The GIT is colonised with microbial communities composed of bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple interactions locally with immune cells that regulate the homeostatic environment and systemically in diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in animal models and in humans, and these sex differences often lead to sex-dependent changes in local GIT inflammation, systemic immunity and susceptibility to a range of inflammatory diseases. The sexually dimorphic microbiome has been termed the 'microgenderome'. Herein, we review the evidence for the microgenderome and contemplate the role it plays in driving sex differences in immunity and disease susceptibility. We further consider the impact that biological sex might play in the response to treatments aimed at manipulating the GIT microbiota, such as prebiotics, live biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal microbial transplant. These alternative therapies hold potential in the treatment of both psychological (e.g., anxiety, depression) and physiological (e.g., irritable bowel disease) disorders differentially affecting males and females.

Why do current strategies for optimal nutritional therapy neglect the microbiome?

Strategies for providing optimal nutritional therapy have evolved over time, with the emphasis on specific directives (such as route, use of immunonutrition, high protein, organ-specific formulas, etc.), achieving variable degrees of success for improving outcomes in the intensive care unit. As the largest immune organ in the body comprising the largest interface between the host and the external environment, the gut can have an amplifying effect on a pattern of dysbiosis, immune dysregulation, and multiple organ failure seen in the critically ill patient. Conversely, maintenance of gut integrity can serve to restore a pattern of homeostasis, appropriate immune responses, symbiosis, and clinical recovery. Simply providing refined polymeric formulas as enteral nutrition may not take full advantage of the potential for optimal outcome that could be derived by giving therapy designed to directly stimulate gut defenses and support the intestinal microbiota. This article describes a series of strategies (such as use of intact whole food formulas, soluble fiber, fecal microbial transplantation, serum bovine immunoglobulin, or agents to promote commensal behavior) that should modulate the gut microbiome and shift the critically ill patient toward a pattern of health and recovery.

Gut microbiota-mediated protection against influenza virus subtype H9N2 in chickens is associated with modulation of the innate responses

Commensal gut microbiota plays an important role in health and disease. The current study was designed to assess the role of gut microbiota of chickens in the initiation of antiviral responses against avian influenza virus. Day-old layer chickens received a cocktail of antibiotics for 12 (ABX-D12) or 16 (ABX-D16) days to deplete their gut microbiota, followed by treatment of chickens from ABX-12 with five Lactobacillus species combination (PROB), fecal microbial transplant suspension (FMT) or sham treatment daily for four days. At day 17 of age, chickens were challenged with H9N2 virus. Cloacal virus shedding, and interferon (IFN)-α, IFN-β and interleukin (IL)-22 expression in the trachea, lung, ileum and cecal tonsils was assessed. Higher virus shedding, and compromised type I IFNs and IL-22 expression was observed in ABX-D16 chickens compared to control, while PROB and FMT showed reduced virus shedding and restored IL-22 expression to levels comparable with undepleted chickens. In conclusion, commensal gut microbiota of chickens can modulate innate responses to influenza virus subtype H9N2 infection in chickens, and modulating the composition of the microbiome using probiotics- and/or FMT-based interventions might serve to promote a healthy community that confers protection against influenza virus infection in chickens.

The journey of gut microbiome – An introduction and its influence on metabolic disorders

Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague. The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota. A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review. Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT). Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.

Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice

ObjectiveThe consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu (Myrciaria dubia) is an Amazonian fruit with a unique...

Safety and efficacy of encapsulated fecal microbiota transplantation for recurrent Clostridium difficile infection: a systematic review.

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.