Study Of Fecal Microbiota Transplantation Research Articles

Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.

Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. BBR was orally administered at doses of 100mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice. We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1β, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota. BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.

Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function

ABSTRACT Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4+, CD8+ T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.

1287P A clinical controlled study of fecal microbiota transplantation in the treatment of advanced cancer with cachexia

Cachexia is one of the most common complications of advanced tumors. About 20 % of patients with malignant tumors die from cachexia.It has been proved that the intestinal microecological environment can be improved by fecal microbiota transplatation to improve the nutritional status of patients.Therefore, we suggest that for patients with cachexia, the use of fecal microbiota transplatation on the basis of standardized nutrition therapy can improve the nutritional status of patients, improve the quality of life of patients. A total of 20 patients with terminal tumor complicated with cachexia were included in the study.According to the propensity score principle, all the selected subjects were divided into the experimental group (10 cases) and the control group (10 cases ).The control group was only given standardized nutrition therapy, and the experimental group was given fecal microbiota transplatation on the basis of standardized nutrition therapy. The paired T test was used to analyze and compare the differences in skeletal muscle, protein, body mass index, hemoglobin, albumin, prealbumin, and triglyceride between the two groups before and after treatment, and the changes in cytokines in the experimental group before and after treatment. There was no statistically significant difference in hemoglobin and other indicators between the two groups before intervention(P>0.05).The skeletal muscle, protein, body mass index, hemoglobin, albumin and prealbumin in the experimental group after transplantation were statistically significant compared with those before transplantation and those in the control group(P<0.05).There was no significant difference in BMI and triglyceride between the experimental group and the control group before and after transplantation(P>0.05).IL-2, IL-6, TNF-α and IFN-γ in the experimental group were significantly higher than those before transplantation(P<0.05). For patients with advanced cancer complicated with cachexia, fecal microbiota transplatation of healthy people can significantly improve the nutritional status of patients, increase nutritional intake, improve the quality of life, which has clinical significance and application value.

Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt’s health effects.

Toward the development of defined microbial therapeutics.

The collection of micro-organisms living in the mammalian gastrointestinal tract, termed the gut microbiota, has been shown to have profound impacts on host health and increasingly is regarded as a viable therapeutic target. Clinical studies of fecal microbiota transplantation have demonstrated potential efficacy of microbiota-based therapies for diseases including Clostridioides difficile infections, inflammatory bowel disease, graft-versus-host disease and cancer. However, the lack of understanding of the active ingredients and potential risks of such therapies pose challenges for clinical application. Meanwhile, efforts are being made to identify effector microbes directly associated with a given phenotype, to establish causality and to devise well-characterized microbial therapeutics for clinical use. Strategies based on defined microbial components will likely enhance the potential of microbiota-targeted therapies.

Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.

The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence. Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children. This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.

Syngeneic Fecal Microbiota Transplant Effectively Attenuated Graft-Versus-Host Disease after Bone Marrow Transplantation in Mice

Introduction: The gut microbiota plays an important role in maintaining intestinal homeostasis and outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT). Post-transplant loss of microbiota diversity in patients has been associated with increased infections, graft-versus-host disease (GVHD), disease relapse, and treatment-related mortality. Case studies of fecal microbiota transplantation (FMT) from healthy donors into patients with steroid-resistant gastrointestinal GVHD suggest that FMT may restore the normal microbiota and improve GVHD. However, it remains unclear what constitutes the “optimal” target microbiota and how different changes in the microbiota may impact GVHD. A particularly interesting question is whether the goal of FMT should be to replicate the original recipient microbiota (recipient FMT) or to transfer the donor microbiota (donor FMT), given that the donor microbiota may be more compatible with the transplanted donor immune system.Methods: To test the hypothesis that donor FMT improves GVHD, we evaluated FMT in the context of our well-established allo-HCT acute GVHD model. T-cell depleted bone marrow (TCD BM) from C57BL/6 mice was transplanted into BALB/c mice without causing GVHD. T cells (1 x 106) from C57BL/6 donors were then be added back to induce GVHD. The BALB/c recipient microbiota was modified by FMT and/or antibiotics. FMT was performed by gavaging freshly collected stool from healthy mice of stem cell donor strain (B6, donor FMT) or recipient strain (BALB/c, recipient FMT). To avoid the potential mechanical injury caused by oral gavage that may affect results, we also evaluated another method of FMT in which allo-HCT recipients were housed with healthy mice, resulting in FMT via coprophagy. To test the effect of antibiotics, some recipient mice were supplied with imipenem and vancomycin in drinking water for three days before FMT. Proliferation of luciferase-labeled T cells was monitored using bioluminescent imaging.Results:As expected, BALB/c mice receiving TCD BM from C57BL/6 had no GVHD, while BALB/c mice receiving TCD BM with 1 x 106 T cells had significant GVHD-related mortality. Contrary to our original hypothesis, donor FMT significantly worsened mortality, while recipient FMT significantly improved mortality (Fig. 1a). The addition of antibiotics particularly exacerbated early morality in the donor FMT group (Fig. 1b) while antibiotics had minimal effect in the recipient FMT setting (Fig. 1c). Interestingly, even in the context of TCD BM alone, donor FMT worsened survival, and this effect was enhanced with the addition of antibiotics (Fig. 1d). Deaths were early and consistent with infection on necropsy.To better understand the mechanisms by which FMT affect survival, we observed T-cell proliferation using bioluminescent imaging of luciferase-labeled T cells. Mice that received recipient FMT had significantly lower luminescence in GVHD major target organs compared to the mice that received donor FMT, indicating less T-cell proliferation (Fig. 2), which is consistent with less T-cell activation and less GVHD.Similar results were seen in co-housing experiments, in which co-housing with healthy recipient animals improved body weight and GVHD scores (Fig. 3). Preliminary 16s ribosomal RNA sequencing results support our hypothesis that FMT changes the microbiome, and these changes in the microbiome are linked to clinical outcomes. We will also explore the pathological changes in the gut microenvironment and the potential mechanism.Conclusion: Recipient FMT in the context of allogeneic HCT helped restore the gut microbiota, suppress T-cell responses in GVHD-associated organs, and ameliorated GVHD. In contrast, donor FMT resulted in a high risk of bacterial infections as well as more severe GVHD. This study may provide crucial clinical guidance for using FMT as a potential treatment for GI GVHD. [Display omitted] DisclosuresSung:Novartis: Research Funding; Merck: Research Funding; Cellective: Research Funding.

Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice

Animal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.

One dog’s waste is another dog’s wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities' abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera's abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

Deciphering functional redundancy in the human microbiome

Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved — implying an ecological property known as functional redundancy. Such functional redundancy has been hypothesized to underlie the stability and resilience of the human microbiome, but this hypothesis has never been quantitatively tested. The origin of functional redundancy is still elusive. Here, we investigate the basis for functional redundancy in the human microbiome by analyzing its genomic content network — a bipartite graph that links microbes to the genes in their genomes. We find that this network exhibits several topological features that favor high functional redundancy. Furthermore, we develop a simple genome evolution model to generate genomic content network, finding that moderate selection pressure and high horizontal gene transfer rate are necessary to generate genomic content networks with key topological features that favor high functional redundancy. Finally, we analyze data from two published studies of fecal microbiota transplantation (FMT), finding that high functional redundancy of the recipient’s pre-FMT microbiota raises barriers to donor microbiota engraftment. This work elucidates the potential ecological and evolutionary processes that create and maintain functional redundancy in the human microbiome and contribute to its resilience.

Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis.

Emerging evidence suggests intestinal microbiota as a central contributing factor to the pathogenesis of Relapsing-Remitting-Multiple-Sclerosis (RRMS). This novel RRMS study evaluated the impact of fecal-microbiota-transplantation (FMT) on a broad array of physiological/clinical outcomes using deep metagenome sequencing of fecal microbiome. FMT interventions were associated with increased abundances of putative beneficial stool bacteria and short-chain-fatty-acid metabolites, which were associated with increased/improved serum brain-derived-neurotrophic-factor levels and gait/walking metrics. This proof-of-concept single-subject longitudinal study provides evidence of potential importance of intestinal microbiota in the pathogenesis of MS, and scientific rationale to help design future randomized controlled trials assessing FMT in RRMS patients.

Engineering the Gut Microbiome for Treatment of Obesity: A Review of Current Understanding and Progress.

Obesity is a complex, multifactorial disease that is increasing in prevalence despite extensive research and efforts to curb it. Over the last decade, gut microbiome has emerged as an important contributor to the pathogenesis of obesity. Microbiome profile is altered in obese phenotype and the causative role of microbiome in obesity is demonstrated in fecal microbiota transplantation studies. Herein, recent evidences supporting the role of gut microbiome in obesity and the current therapies designed to engineer gut microbiome for treatment of obesity will be reviewed. The microbial enterotypes associated with obesity is outlined, and the gut microbiota-driven metabolism and low-grade inflammation linking gut microbiome and obesity is examined. How the different intrinsic and extrinsic factors such as host genetics, mode of childbirth delivery, diet, lifestyle habits and use of antibiotics influence the composition of the gut microbiome in the development of obesity is evaluated. Also, the efficacy of current microbiome-based therapies in the forms of prebiotics, probiotics and engineered microbes that are used to manipulate gut microbiome in treating obesity is discussed.

Fecal Microbiota Transplantation for Irritable Bowel Syndrome

Intestinal dysbiosis may contribute to the pathogenesis of irritable bowel syndrome (IBS), but studies of fecal microbiota transplantation (FMT) to

Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids).Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography.Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported.Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks.ClinicalTrials.gov ID: NCT03333291.Trial registration: ClinicalTrials.gov identifier: NCT03333291.

Effects of Early Intervention With Maternal Fecal Bacteria and Antibiotics on Liver Metabolome and Transcription in Neonatal Pigs.

The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (>109/mL), respectively, on days 1–6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of arachidonate 12-lipoxygenase (ALOX12), acetyl-CoA acyltransferase 2 (ACAA2), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), glutamic–pyruvic transaminase 2 (GPT2) and argininosuccinate synthase 1 (ASS1) were downregulated (P < 0.05) by AM on day 7, and that the mRNA expressions of arachidonate 15-lipoxygenase (ALOX15), CYP1A2 and GPT2 were downregulated (P < 0.05) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (P < 0.05) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced (P < 0.05) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health.

2092 A multicenter study of fecal microbiota transplantation for Clostridium difficile infection in children

OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.

Treatment With Fecal Microbiota Transplantation: The Need for Complete Methodological Reporting for Clinical Trials

The editorialist discusses Bafeta and colleagues' systematic review, which examined the methods described in 85 studies of fecal microbiota transplantation.

Long-term Follow-up Study of Fecal Microbiota Transplantation for Severe and/or Complicated Clostridium difficile Infection: A Multicenter Experience.

Our aim was to investigate fecal microbiota transplantation (FMT) efficacy in patients with severe and/or complicated Clostridium difficile infection (CDI). FMT is successful for recurrent CDI, although its benefit in severe or complicated CDI has not specifically been evaluated. A multicenter long-term follow-up study was performed in patients who received FMT for severe and/or complicated CDI (diagnosed using standard criteria). Pre-FMT and post-FMT questionnaires were completed. Study outcomes included cure rates and time to resolution of symptoms. A total of 17 patients (82% inpatients, 18% outpatients) were included (76.4% women; mean age, 66.4 y; mean follow-up, 11.4 mo). Patients had severe and complicated (76.4%) or either severe or complicated (23.6%) CDI. Sixteen patients (94.1%) had diarrhea, which resolved in 12 (75%; mean time to resolution, 5.7 d) and improved in 4 (25%) after FMT. Eleven patients (64.7%) had abdominal pain, which resolved in 8 (72.7%; mean time to resolution, 9.6 d) and improved in 3 (27.3%) after FMT. Two of 17 patients experienced early CDI recurrence (≤90 d) after FMT (primary cure rate, 88.2%); and in 1 patient, a second FMT resulted in cure (secondary cure rate, 94.1%). Late CDI recurrence (≥90 d) was seen in 1 of 17 patients (5.9%) in association with antibiotics and was successfully treated with a repeat FMT. No adverse effects directly related to FMT occurred. FMT was successful and safe in this cohort of patients with severe or complicated CDI. Primary and secondary cure rates were 88.2% and 94.1%, respectively.

P-214 A Study of Fecal Microbiota Transplantation in Pediatric Patients with Inflammatory Bowel Disease

P-214 A Study of Fecal Microbiota Transplantation in Pediatric Patients with Inflammatory Bowel Disease

Guidance on Preparing an Investigational New Drug Application for Fecal Microbiota Transplantation Studies

Fecal microbiota transplantation (FMT) is an effective treatment for Clostridium difficile infections that are refractory to antibiotic therapy. Because of the important roles of the microbiota in the function of the gastrointestinal tract and other aspects of human physiology, there is a growing interest in studying FMT for other clinical indications. The US Food and Drug Administration regulates clinical studies to evaluate the safety and efficacy of FMT. Studies of FMT for recurrent Clostridium difficile infection or other indications could require submission of an investigational new drug application. Most academic physicians and investigators do not have the regulatory experience necessary to undertake this process. We provide guidance to researchers on the preparation and submission of investigational new drug applications to study FMT.