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Background: Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases., Methods: We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool., Results: Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities., Conclusions: Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ebrahimi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gastrointestinal disease (GI) is the most common illness in pre-weaned dairy calves. Therefore, effective strategies to manipulate the microbiome of dairy calves under commercial dairy operations are of great importance to improve animal health and reduce antimicrobial usage. The objective of this study was to develop a farm-specific FMT product and to investigate its effects on clinical outcomes and fecal microbial composition of dairy calves. The FMT product was derived from feces from healthy donors (5-24 days of age) raised in the same calf ranch facility as the FMT recipients. Healthy and diarrheic calves were randomly enrolled to a control (n = 115) or FMT (n = 112) treatment group (~36 g of processed fecal matter once daily for 3 days). Fecal samples were collected at enrollment and again 9 days later after the first FMT dose. Although the FMT product was rich in organisms typically known for their beneficial probiotic properties, the FMT therapy did not prevent or ameliorate GI disease in dairy calves. In fact, calves that received FMT were less likely to recover from GI disease, and more likely to die due to GI disease complications. Fecal microbial community analysis revealed an increase in the alpha-diversity in FMT calves; however, no major differences across treatment groups were observed in the beta-diversity analysis. Calves that received FMT had higher relative abundance of an uncultured organism of the genus Lactobacillus and Lactobacillus reuteri on day 10. Moreover, FMT calves had lower relative abundance of Clostridium nexile and Bacteroides vulgatus on day 10. Our results indicate the need to have an established protocol when developing FMT products, based on rigorous inclusion and exclusion criteria for the selection of FMT donors free of potential pathogens, no history of disease or antibiotic treatment., Competing Interests: The authors have declared that no competing interests exist.

Background: There are limited studies investigating the use of fecal microbial transplant (FMT) in dogs with inflammatory bowel disease (IBD). The aim of this preliminary study was to assess the feasibility of adding FMT to standard therapy (corticosteroids and a hypoallergenic diet) for dogs with IBD and to and to describe the changes in measured outcomes after 30 days of treatment., Methods: Thirteen client-owned dogs with IBD were enrolled in this double blinded, randomized clinical trial. All dogs received corticosteroid therapy and a hypoallergenic diet; dogs were randomized to receive either placebo or FMT. Measured outcomes included the canine chronic enteropathy clinical activity index (CCECAI) at 1 week and 1 month after enrolment. Fecal microbiota were analyzed after extracting DNA from fecal samples and profiling using 16S amplicon sequencing. Dogs in the placebo group not responding to treatment after 1 month were offered FMT., Results: The CCECAI significantly decreased over time in both groups (p = 0.001). There were no significant differences between the CCECAI of the placebo and FMT group at each time point (F test from ANOVA, p = 0.40). No adverse effects were reported in the 30 days following FMT., Conclusions: The addition of FMT to standard therapy for IBD was feasible. No significant differences were observed in the CCECAI between groups at each time point. Large scale clinical trials can be performed using these methods to evaluate the longer term effect of FMT on clinical signs, microbial diversity, and other outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS coronavirus-2 (SARS-CoV-2) transmission via FMT, many stool banks were forced to temporarily halt and adjust donor activities., Goal: The evaluation of a strategy to effectively continue stool banking activities during the ongoing COVID-19 pandemic., Study: To restart our stool banking activities after an initial halt, we implemented periodic SARS-CoV-2 screening in donor faeces and serum, and frequent donor assessment for COVID-19 related symptoms. FMT donor and recipient data obtained before (2016-2019) and during the COVID-19 pandemic (March 2020-August 2021) were compared to assess stool banking efficacy., Results: Two out of ten donors developed COVID-19. No differences during versus before the COVID-19 pandemic were observed in the number of approved faeces donations (14 vs 22/month, p = 0.06), FMT requests for rCDI (3.9 vs 4.3/month, p = 0.6); rCDI patients eligible for FMT (80.6% vs 73.3%, p = 0.2); rCDI cure rate (90.3% vs 89.2%, p = 0.9); CDI-free survival (p = 0.7); the number of non-rCDI patients treated with FMT (0.5/month vs 0.4/month), and the number of possibly FMT related adverse events (9.5% vs 7.8%, p = 0.7). Two FMTs for rCDI were delayed due to COVID-19., Conclusions: There is a continued need for FMT treatment of rCDI during the COVID-19 pandemic. Appropriate donor screening and SARS-CoV-2 infection prevention measures can be implemented in existing protocols without increasing the burden for donors, and allow safe, effective and efficient FMT during the ongoing COVID-19 pandemic. Stool banks should evaluate their SARS-CoV-2 donor screening protocols for long-term sustainability and efficacy, and share their experiences to help the utilisation, standardisation and improvement of stool banks worldwide., Competing Interests: The authors have declared that no competing interests exist.

The concept of successional trajectories describes how small differences in initial community composition can magnify through time and lead to significant differences in mature communities. For many animals, the types and sources of early-life exposures to microbes have been shown to have significant and long-lasting effects on the community structure and/or function of the microbiome. In modern commercial poultry production, chicks are reared as a single age cohort and do not directly encounter adult birds. This scenario is likely to initiate a trajectory of microbial community development that is significantly different than non-industrial settings where chicks are exposed to a much broader range of environmental and fecal inocula; however, the comparative effects of these two scenarios on microbiome development and function remain largely unknown. In this work, we performed serial transfers of cecal material through multiple generations of birds to first determine if serial transfers exploiting the ceca in vivo, rather than the external environment or artificial incubations, can produce a stable microbial community. Subsequently, we compared microbiome development between chicks receiving this passaged, i.e. host-selected, cecal material orally, versus an environmental inoculum, to test the hypothesis that the first exposure of newly hatched chicks to microbes determines early GI microbiome structure and may have longer-lasting effects on bird health and development. Cecal microbiome dynamics and bird weights were tracked for a two-week period, with half of the birds in each treatment group exposed to a pathogen challenge at 7 days of age. We report that: i) a relatively stable community was derived after a single passage of transplanted cecal material, ii) this cecal inoculum significantly but ephemerally altered community structure relative to the environmental inoculum and PBS controls, and iii) either microbiome transplant administered at day-of-hatch appeared to have some protective effects against pathogen challenge relative to uninoculated controls. Differentially abundant taxa identified across treatment types may inform future studies aimed at identifying strains associated with beneficial phenotypes., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease., Methods: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted., Results: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure., Conclusions: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis., Purpose: This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis., Methods: The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons., Results: Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles., Conclusions: Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity., Methods: To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing., Results and Conclusions: In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor., Competing Interests: The authors have declared that no competing interests exist.

Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact., Competing Interests: EA is co-founder of Finch Therapeutics and is on the Board of Directors of OpenBiome. CZ, PP, SB, and MO are employed by OpenBiome. These commercial sources of funding do not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Although systematic evaluation has confirmed the efficacy of fresh fecal microbiota transplantation (FMT) for treatment of recurrent and/or refractory and/or relapse C. difficile infection (RCDI), it lacks the support of well-designed randomized controlled trials (RCTs), and the latest guidelines do not optimize the management of FMT. In this paper, we focus on an in-depth study of fresh FMT and fecal infusion times to guide clinical practice., Methods: We reviewed studies in PubMed, Medline, Embase, the Cochrane library and Cochrane Central written in English. The retrieval period was from the establishment of the databases to September 20th, 2018. The retrieval objects were published RCTs of RCDI treated by fresh FMT. The intervention group was fresh FMT group, while the control group included antibiotic therapy or placebo or frozen FMT or capsule. The primary and secondary outcomes were the clinical remission of diarrhea without relapse after 8-17 weeks and the occurrence of severe adverse events, respectively. Subgroup analysis analyzed the effect of single and multiple fecal infusions. Two authors independently completed the information extraction and assessed risk of bias and overall quality of the evidence., Results: 8 randomized controlled trials met the inclusion criteria, involving 537 patients (273 in the fresh FMT group and 264 in the control group). The recurrence rate of clinical diarrhea in the fresh FMT group was 11.0% (30/273), which was significantly lower than the control group (24.6%, 65/264; P < 0.05); the pooled relative risk (RR) was 0.38 (95%CI:0.16-0.87; I2 = 67%; P = 0.02) in the fresh FMT group, and the clinical heterogeneity was significant and random effects model was used; However, there was no significant difference neither for the effect of antibiotic treatment/frozen feces transplanted by enema (RR = 1.07; 95%CI: 0.64-1.80; I2 = 0%; P = 0.79) or capsule/frozen feces transplanted by colonoscopy (RR = 0.42; 95%CI: 0.05-3.94; I2 = 43%; P = 0.45) compared with fresh FMT. The subgroup analysis showed that FMT by multiple infusions could effectively and significantly (RR = 0.24; 95%CI:0.10-0.58; I2 = 0%; P = 0.001) improve the clinical diarrhea remission rate. Most mild to moderate adverse events caused by FMT were self-limited and could be quickly alleviated; no severe adverse events happened because of FMT., Conclusions: Overall, the use of fresh feces for bacterial transplantation was the best efficiency for RCDI compared to antibiotic therapy or placebo. The fecal transmission method by enema was not ideal, but capsules or frozen feces transported by colonoscopy could be an alternative treatment compared to fresh FMT. For patients with severe RCDI, multiple fecal transplants can effectively improve their diarrhea remission rate. The focus of future research should be on how to standardize the production of capsules or frozen feces to better guide the clinical management of RCDI patients by FMT., Competing Interests: The authors have declared that no competing interests exist.

Background: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI)., Aims: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema., Methods: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied., Results: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema., Conclusions: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product., Trial Registration: ClinicalTrials.gov NCT02449174., Competing Interests: The authors have declared that no competing interests exist.

Background: Clostridium difficile infection (CDI) caused by ribotype 002 strain is associated with poor outcomes in Chinese patients. Fecal microbiota transplantation (FMT) is an effective but costly treatment for CDI. We aimed to examine potential cost-effectiveness of ribotype-guided FMT in Chinese patients with severe CDI., Methods: A decision-analytic model was designed to simulate outcomes of ribotype 002-guided FMT versus vancomycin treatment in Chinese patients with severe CDI in the hospital setting. Outcome measures included mortality rate; direct medical cost; and quality-adjusted life year (QALY) loss for CDI. Sensitivity analysis was performed to examine robustness of base-case results., Results: Comparing to vancomycin treatment, ribotype-guided FMT group reduced mortality (11.6% versus 17.1%), cost (USD8,807 versus USD9,790), and saved 0.472 QALYs in base-case analysis. One-way sensitivity analysis found the ribotype-guided FMT group to remain cost-effective when patient acceptance rate of FMT was >0.6% and ribotype 002 prevalence was >0.07%. In probabilistic sensitivity analysis, ribotype-guided FMT gained higher QALYs at 100% of simulations with mean QALY gain of 0.405 QALYs (95%CI: 0.400-0.410; p<0.001). The ribotype-guided group was less costly in 97.9% of time, and mean cost-saving was USA679 (95%CI: 670-688; p<0.001)., Conclusions: In the present model, ribotype-guided FMT appears to be a potential option to save QALYs and cost when comparing with vancomycin. The cost-effectiveness of ribotype-guided FMT is subject to the patient acceptance to FMT and prevalence of ribotype 002., Competing Interests: The authors have declared that no competing interests exist.

Fecal microbiota transplantation has been proposed as a therapeutic approach for chronic constipation. This randomized, controlled trial aimed to compare the effects of conventional treatment alone (control) with additional treatment with FMT (intervention) in patients with slow-transit constipation (STC). Adults with STC were randomized to receive intervention or control treatment. The control group received education, behavioral strategies, and oral laxatives. The intervention group was additionally provided 6 days of FMT. The primary endpoint was the clinical cure rate (proportion of patients achieving a mean of ≥ three complete spontaneous bowel movements [CSBMs] per week]. Secondary outcomes and safety parameters were assessed throughout the study. Sixty patients were randomized to either conventional treatment alone (n = 30) or FMT (n = 30) through a nasointestinal tube. There were significant differences between the intervention group and control group in the clinical improvement rate (intention-to-treat [ITT]: 53.3% vs. 20.0%, P = 0.009), clinical cure rate (ITT: 36.7% vs. 13.3%, P = 0.04), mean number of CSBMs per week (ITT: 3.2 ± 1.4 vs. 2.1 ± 1.2, P = 0.001), and the Wexner constipation score (ITT: 8.6 ± 1.5 vs. 12.7 ± 2.5, P < 0.00001). Compared with the control group, the intervention group showed better results in the stool consistency score (ITT: 3.9 vs. 2.4, P < 0.00001) and colonic transit time (ITT: 58.5 vs. 73.6 h, P < 0.00001). The intervention group had more treatment-related adverse events than did the control group (50 vs. 4 cases). FMT was significantly more effective (30% higher cure rate) for treatment of STC than conventional treatment. No serious adverse events were observed., Competing Interests: The authors have declared that no competing interests exist.

Fecal microbiota transplantation is a compelling treatment for recurrent Clostridium difficile infections, with potential applications against other diseases associated with changes in gut microbiota. But variability in fecal bacterial communities-believed to be the therapeutic agent-can complicate or undermine treatment efficacy. To understand the effects of transplant preparation methods on living fecal microbial communities, we applied a DNA-sequencing method (PMA-seq) that uses propidium monoazide (PMA) to differentiate between living and dead fecal microbes, and we created an analysis pipeline to identify individual bacteria that change in abundance between samples. We found that oxygen exposure degraded fecal bacterial communities, whereas freeze-thaw cycles and lag time between donor defecation and transplant preparation had much smaller effects. Notably, the abundance of Faecalibacterium prausnitzii-an anti-inflammatory commensal bacterium whose absence is linked to inflammatory bowel disease-decreased with oxygen exposure. Our results indicate that some current practices for preparing microbiota transplant material adversely affect living fecal microbial content and highlight PMA-seq as a valuable tool to inform best practices and evaluate the suitability of clinical fecal material., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MBS, ZK are employees of OpenBiome and consultants, research advisors, and shareholders of Finch Therapeutics. EJA is a consultant and research advisor of OpenBiome and Finch Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Clostridium difficile infection (CDI) is characterized by high rates of recurrence, resulting in substantial health care costs. The aim of this study was to analyze the cost-effectiveness of treatments for the management of second recurrence of community-onset CDI in France., Methods: We developed a decision-analytic simulation model to compare 5 treatments for the management of second recurrence of community-onset CDI: pulsed-tapered vancomycin, fidaxomicin, fecal microbiota transplantation (FMT) via colonoscopy, FMT via duodenal infusion, and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) among the 5 treatments. ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses., Results: Three strategies were on the efficiency frontier: pulsed-tapered vancomycin, FMT via enema, and FMT via colonoscopy, in order of increasing effectiveness. FMT via duodenal infusion and fidaxomicin were dominated (i.e. less effective and costlier) by FMT via colonoscopy and FMT via enema. FMT via enema compared with pulsed-tapered vancomycin had an ICER of €18,092/QALY. The ICER for FMT via colonoscopy versus FMT via enema was €73,653/QALY. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations showed that FMT via enema was the most cost-effective strategy in 58% of simulations and FMT via colonoscopy was favored in 19% at a willingness-to-pay threshold of €32,000/QALY., Conclusions: FMT via enema is the most cost-effective initial strategy for the management of second recurrence of community-onset CDI at a willingness-to-pay threshold of €32,000/QALY., Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: TG reports personal fees from Astellas and MSD, outside the submitted work. All authors report no competing interests relevant to this article. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Fecal microbiota transplantation is being assessed as a treatment for chronic microbiota-related diseases such as ulcerative colitis. Results from an initial randomized trial suggest that remission rates depend on unobservable features of the fecal donors and observable features of the patients. We use mathematical modeling to assess the efficacy of pooling stools from different donors during multiple rounds of treatment. In the model, there are two types of patients and two types of donors, where the patient type is observable and the donor type (effective or not effective) is not observable. In the model, clinical outcomes from earlier rounds of treatment are used to estimate the current likelihood that each donor is effective, and then each patient in each round is treated by a pool of donors that are currently deemed to be the most effective. Relative to the no-pooling case, pools of size two or three significantly increase the proportion of patients in remission during the first several rounds of treatment. Although based on data from a single randomized trial, our modeling suggests that pooling of stools - via daily cycling of encapsulated stool from several different donors - may be beneficial in fecal microbiota transplantation for chronic microbiota-related diseases., Competing Interests: The authors have declared that no competing interests exist.

Objective: There were no reports on predicting long-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). This study aimed to detect short-term changes of cytokines and C-reactive protein (CRP) in patients with UC undergoing FMT, and to evaluate the predictive value of CRP and cytokines for the long-term efficacy of FMT., Methods: Nineteen patients with moderate to severe UC (Mayo score ≥ 6) were treated with single fresh FMT through mid-gut. Serum samples were collected before and three days post-FMT. Clinical responses were evaluated by a minimum follow-up of three months. Patients with clinical improvement and remission at the assessment point of three-month were included as response group, while patients without clinical improvement or remission were included as non-response group. Serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, IFN-γ, TNF, TNFR-1, TNFR-2, MCP-1, G-CSF, GM-CSF) and CRP were assayed to predict the clinical response of FMT., Results: In total, 10.5% (2/19) of patients achieved clinical remission and 47.4% (9/19) achieved clinical improvement (Response group, including clinical remission and clinical improvement), 42.1% (8/19) failed to benefit from FMT (Non-response group). In both Response group and Non-response group, the level of CRP at three days after FMT didn't show significant decrease compared with that before FMT (p>0.05). However, in Response group, CRP level at three months after FMT decreased significantly than that before FMT (p<0.05). Compared with healthy controls (n = 9), patients with UC showed a higher baseline level of serum IL-6, TNFR-2 and G-CSF, and a lower level of IL-2 and IL-4 (p<0.05). In both Response group and Non-response group, none of the eleven detectable cytokines showed a significant difference between the value at three days after FMT and that before FMT (p>0.05)., Conclusions: Patients with moderate to severe UC presented a complex disorder of cytokines. However, the efficacy of FMT for UC might not be predicted by the short-term surveillance of cytokines and CRP.

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.

A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity. Rats were fed either a standard or high-fructose diet. Groups of fructose-fed rats were treated with either antibiotics or faecal samples from control rats by oral gavage. Body composition, plasma metabolic parameters and markers of tissue oxidative stress were measured in all groups. A 16S DNA-sequencing approach was used to evaluate the bacterial composition of the gut of animals under different diets. The fructose-rich diet induced markers of metabolic syndrome, inflammation and oxidative stress, that were all significantly reduced when the animals were treated with antibiotic or faecal samples. The number of members of two bacterial genera, Coprococcus and Ruminococcus, was increased by the fructose-rich diet and reduced by both antibiotic and faecal treatments, pointing to a correlation between their abundance and the development of the metabolic syndrome. Our data indicate that in rats fed a fructose-rich diet the development of metabolic syndrome is directly correlated with variations of the gut content of specific bacterial taxa.