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Background & Aims: Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population., Methods: We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 10 11 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24., Results: A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups., Conclusions: CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133)., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Abstract: Fecal microbiota transplantation (FMT) prevents recurrent Clostridioides difficile infections (rCDI) in patients with inflammatory bowel disease. Bezlotoxumab is also indicated to prevent rCDI. We assess the impact of FMT in combination with bezlotoxumab in patients with inflammatory bowel disease and rCDI. We conducted a multicenter randomized placebo-controlled trial. All received a single colonoscopic FMT. Patients were randomized 1:1 to receive bezlotoxumab or placebo. Sixty-one patients were enrolled (30 received treatment and 31 received placebo). Overall, 5 participants (8%) experienced a CDI recurrence; 4 in the treatment arm, 1 in the placebo arm (13% vs 3%, P = 0.15). There was no clear benefit to the combination approach compared with FMT alone., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies., Aim: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections., Methods: A narrative review was performed to evaluate the current literature between 1986 and 2023., Results: The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon., Conclusion: Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future., (© 2024 John Wiley & Sons Ltd.)

Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms., Competing Interests: Potential conflicts of interest. C. R. K. reports consulting fees from Sebela Pharmaceuticals; support for attending the 2023 International Scientific Association of Probiotics and Prebiotics (ISPAA) annual meeting as the invited cochair; serving on the clinical advisory board of OpenBiome; and serving as section chair of Basic and Clinical Intestinal Disorders with the American Gastroenterological Association. J. A. reports grant support from Merck, Janssen, Pfizer, and the National Institutes of Health (all unrelated to this work). J. A. reports receiving consultancy fees from Janssen, Pfizer, AbbvVie, Iterative Scopes, Finch Therapeutics, Seres Therapeutics, Ferring, GlaxoSmithKline, Merck, Bristol Myers Squibb, Roivant, and Adiso; payments for speaking with Bristol Myers Squibb, AbbVie, and Janssen; payments for testimony from Finch Therapeutics; and participation on a data and safety monitoring board for Merck. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Goals: Characterize and compare the risk of Clostridioides difficile infection (CDI) and cytomegalovirus colitis (CMVC) after initiation of vedolizumab or anti-tumor necrosis factor (TNF)α agents for ulcerative colitis (UC)., Background: Immunosuppression is a risk factor for gastrointestinal infections including CDI and CMVC among patients with UC; however, the risk according to the biological class is poorly understood., Study: A retrospective cohort study of adults with UC involving the initiation of vedolizumab or anti-TNFα agents during June 1, 2014 to December 31, 2020 was conducted at a large academic health system. The primary outcomes for both CDI and CMVC analyses were first CDI or CMVC after biological initiation. The secondary outcome for the CDI analysis was severe CDI (>10,000 white blood cells or serum creatinine >1.5 mg/dL). Independent variables included demographics and UC history/severity factors. Inverse probability of treatment weighted Cox regression was performed to assess the hazard of CDI by biological group. Due to few outcomes, CMVC was reported descriptively., Results: A total of 805 UC patients initiated vedolizumab (n=195) or anti-TNFα agents (n=610). There were 43 CDIs and 11 severe CDIs over 1436 patient-years. The inverse probability of treatment weighted Cox regression demonstrated no association between CDI and vedolizumab versus anti-TNFα (hazard ratio 0.33, 95% confidence interval 0.05-2.03), but identified a significantly lower hazard of severe CDI for vedolizumab versus anti-TNFα (hazard ratio 0.10, 95% confidence interval 0.01-0.76). There were 5 cases of CMVC, all in the anti-TNFα group., Conclusions: There was a lower adjusted risk of severe CDI but not total CDI associated with vedolizumab. CMVC was not observed after initiating vedolizumab. These findings may provide reassurance regarding the use of vedolizumab when also considering the risk of gastrointestinal infections., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection., Competing Interests: Disclosures: All relevant financial relationships have been mitigated. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0754.

Background: Recurrent or chronic antibiotic therapy is a therapeutic hallmark of chronic antibiotic-dependent pouchitis (CADP) or Crohn's-like disease of the pouch. Antibiotics alter the gut microbiome, which may increase the risk of Clostridioides difficile infection (CDI). The aim of this study was to determine the prevalence of CDI in patients with CADP and Crohn's-like disease of the pouch., Methods: We conducted a retrospective cohort study of patients with CADP or Crohn's-like disease of the pouch at a tertiary academic medical center. The primary outcome was prevalence of CDI. Secondary outcomes included antibiotic therapy at the time of CDI diagnosis, treatment regimens for CDI, and subsequent outcomes., Results: Overall, 18 of 198 (9.1%) included patients developed CDI. Treatment with antibiotics at the time of CDI diagnosis occurred in 7 of 18 (39%) patients. Preoperative history of CDI was significantly associated with increased risk of developing CDI following ileal pouch anal anastomosis (IPAA) compared with those with no prior history of CDI (12 of 18 [67%] vs 11 of 180 [6%]; P < .001). In 16 of 18 (89%) patients, CDI treatment was initiated with predominantly oral vancomycin (72%) or metronidazole (17%)., Conclusion: Although chronic inflammatory conditions of the pouch arise postoperatively, the prevalence of CDI in this population appears to be similar compared with the general population of patients with inflammatory bowel disease prior to and post IPAA. Preoperative CDI appears to be the greatest risk for postoperative CDI and may require extra vigilance in the assessment of CDI after IPAA., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infections (rCDIs) nonresponsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients because of medical comorbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicenter, prospective, real-world cohort., Methods: Clinical outcomes and adverse events after FMT performed for rCDI at 6 sites were captured in a prospective registry. FMT was performed using 1 of 2 standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. The FMT administration route was determined by the treating physician. The rCDI cure rate was assessed at 1 and 2 months. Safety data were collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure., Results: A total of 301 FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI, 82%-90%) at 1 month and 81% (95% CI, 75%-86%) at 2 months. There was no difference in the 1-month or 2-month cure rate between cap-FMT and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression. In addition, post-FMT antibiotic use was associated with FMT failure at 2 months. One serious adverse event was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified., Conclusions: Cap-FMT using freeze-dried capsules has a similar safety and effectiveness profile compared with colo-FMT, without the procedural risks of colonoscopy. Although highly effective overall, patient selection is a key factor to optimizing FMT success., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis., Aims: To define stool BA dynamics in patients with primary CDI and to explore signatures predicting recurrence METHODS: Weekly stool samples were collected from patients with primary CDI from the last day of anti-CDI therapy until recurrence or, otherwise, through 8 weeks post-completion. Ultra-high performance liquid chromatography-mass spectrometry was used to profile BAs. Stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence., Results: Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post-antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post-treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non-relapsing patients (β = 0.056; likelihood ratio test p = 0.018). A joint longitudinal-survival model identified five stool BAs with area under the receiver operating characteristic curve >0.73 for predicting recurrence within 9 days post-CDI treatment., Conclusions: Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence., (© 2022 John Wiley & Sons Ltd.)

Background: Clostridioides difficile infection (CDI) is the most common hospital acquired infection in the USA, with recurrence rates > 15%. Although primary CDI has been extensively linked to gut microbial dysbiosis, less is known about the factors that promote or mitigate recurrence. Moreover, previous studies have not shown that microbial abundances in the gut measured by 16S rRNA amplicon sequencing alone can accurately predict CDI recurrence., Results: We conducted a prospective, longitudinal study of 53 non-immunocompromised participants with primary CDI. Stool sample collection began pre-CDI antibiotic treatment at the time of diagnosis, and continued up to 8 weeks post-antibiotic treatment, with weekly or twice weekly collections. Samples were analyzed using (1) 16S rRNA amplicon sequencing, (2) liquid chromatography/mass-spectrometry metabolomics measuring 1387 annotated metabolites, and (3) short-chain fatty acid profiling. The amplicon sequencing data showed significantly delayed recovery of microbial diversity in recurrent participants, and depletion of key anaerobic taxa at multiple time-points, including Clostridium cluster XIVa and IV taxa. The metabolomic data also showed delayed recovery in recurrent participants, and moreover mapped to pathways suggesting distinct functional abnormalities in the microbiome or host, such as decreased microbial deconjugation activity, lowered levels of endocannabinoids, and elevated markers of host cell damage. Further, using predictive statistical/machine learning models, we demonstrated that the metabolomic data, but not the other data sources, can accurately predict future recurrence at 1 week (AUC 0.77 [0.71, 0.86; 95% interval]) and 2 weeks (AUC 0.77 [0.69, 0.85; 95% interval]) post-treatment for primary CDI., Conclusions: The prospective, longitudinal, and multi-omic nature of our CDI recurrence study allowed us to uncover previously unrecognized dynamics in the microbiome and host presaging recurrence, and, in particular, to elucidate changes in the understudied gut metabolome. Moreover, we demonstrated that a small set of metabolites can accurately predict future recurrence. Our findings have implications for development of diagnostic tests and treatments that could ultimately short-circuit the cycle of CDI recurrence, by providing candidate metabolic biomarkers for diagnostics development, as well as offering insights into the complex microbial and metabolic alterations that are protective or permissive for recurrence. Video Abstract., (© 2022. The Author(s).)

Background and Aim: Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal microbiota transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential fecal microbiota transplantation (sFMT) protocol for FCDI compared with current standard therapy., Methods: A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100 000 per QALY., Results: Sequential fecal microbiota transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit., Conclusions: An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited., Methods: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling., Results: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04)., Conclusion: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis., Methods: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT., Results: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death., Conclusions: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD., Recent Findings: Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed., Summary: CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios., (Copyright © 2021 by The American College of Gastroenterology.)

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.

Background: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI); however, a small percentage of patients fail to achieve cure even after two FMTs. This high-risk cohort remains poorly understood., Methods: We performed a multicenter, multinational retrospective review of patients that underwent at least one FMT for a CDI indication at four academic FMT referrals. Patients' data including CDI, FMT, and FMT variables were assessed. The primary outcome was FMT failure after a second FMT defined as persistent diarrhea and positive laboratory test for C. difficile (PCR or toxin) despite a second FMT within 8 weeks of the first FMT. A multivariable logistic regression model was performed to determine predictors of second FMT failure., Results: A total of 540 patients received at least one FMT during the study period, of which 432 patients had success following the first FMT, 108 had documented failure (25%). Among those who failed the first FMT, 63 patients received a second FMT, of which 36 achieved cure, and 24 had documented failure after the second FMT. Patients that failed the first FMT but did not receive a second FMT and those lost to follow-up were excluded leaving 492 patients included in the analysis. The second FMT failure rate was 4.8% (24/492). Risk factors for second FMT failure identified by multivariable logistic regression included: inpatient status (OR 7.01, 95% CI: 2.37-20.78), the presence of pseudomembranes (OR 3.53, 95% CI: 1.1-11.33), and immunocompromised state (OR 3.56, 95% CI: 1.45-8.72) at the time of first FMT., Conclusion: This study identifies clinically relevant risk factors predictive of failing a second FMT. Clinicians can use these variables to help identify high-risk patients and provide a better-informed consent regarding the possibility of needing multiple FMTs.

Background & Aims: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers., Methods: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes., Results: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%)., Conclusions: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT., (Copyright © 2021. Published by Elsevier Inc.)

Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum , we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities., Competing Interests: Competing interests: AG reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie Srl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. BHM reports personal fees from Finch Therapeutics Group. CRK has served as a clinical advisor, with no financial compensation, for OpenBiome since 2013; she is a local principal investigator for the PRISM-3 clinical trial, for which her institution receives some salary support for a research coordinator and compensation from Finch Therapeutics Group for each patient enrolled. FZ reports grants from the non-profit China Microbiota Transplantation System (fmtBank) and has a patent for GenFMTer for separating microbiota issued to FMT medical. GC has received personal fees for acting as advisor for Ferring Therapeutics. GI has received personal fees for acting as speaker from Biocodex, Danone, Metagenics, and for acting as consultant/advisor from Ferring Therapeutics, Giuliani, Metagenics. HS reports personal fees from Danone, Enterome, Takeda, AbbVie, Roche, Amgen, Danone, BiomX, Ferring, BMS, Astellas, MSD, Novartis, Tillotts Pharma, and Biose, and grants from Biocodex, Danone and BiomX, and is a co-founder of Exeliom Biosciences. JJK and EJK report grants from Vedanta Biosciences. JRA reports personal fees from Finch Therapeutics and has a non-financial relationship with OpenBiome as a scientific advisor. MF reports personal fees from Finch Therapeutics Group, Rebiotix, Takeda, AbbVie and Janssen. SCN reports grants from Ferring and personal fees from Takeda, AbbVie, Janssen and Tillotts. SPC reports non-financial support from Janssen and personal fees from Shire, Ferring, Microbiotica and Pfizer. ZK is an employee and shareholder of Finch Therapeutics and is an unpaid special advisor for OpenBiome., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Goals: We investigated the long-term efficacy and safety of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridioides difficile infection (rCDI)., Background: FMT has emerged as a promising therapy for patients with rCDI unresponsive to standard medical therapy, though long-term efficacy and safety data are scarce., Materials and Methods: A multicenter retrospective study was performed on patients treated with FMT for rCDI with ≥6 months of clinical follow-up post-FMT. Patients were contacted to document sustained efficacy, potential adverse events, and antibiotic exposure. The electronic medical record was reviewed to confirm patient-reported outcomes and obtain additional data. The primary outcome was sustained cure, as defined by the absence of Clostridioides difficile infection (CDI) at any timepoint after FMT., Results: Of 528 patients treated, 207 were successfully contacted. The mean follow-up post-FMT was 34 (range: 6 to 84) months. One hundred fifty-seven patients (75.8%) reported sustained cure at the time of follow-up. One hundred patients (48%) reported the use of antibiotics for non-CDI indications post-FMT, of whom 11 (11%) had experienced CDI post-FMT. Fifty-two of the original 528 patients (9.8%) treated with FMT had died at the time of follow-up contact; none were felt attributable to the procedure. New medical conditions or diagnoses post-FMT were reported in 105 patients (50.5%). Fifteen reported improvement post-FMT in previously diagnosed medical conditions., Conclusions: In this largest and longest study to date on efficacy and safety after FMT for treatment of rCDI, we found that the majority of patients experienced long-term cure. Although a number of new conditions developed post-FMT, there was no clustering of diseases associated with dysbiosis.

Background & Aims: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI). FMT cures nearly 80% of patients with severe or fulminant CDI (SFCDI) when utilized in a sequential manner. We compared outcomes of hospitalized patients before and after implementation of an FMT program for SFCDI and investigated whether the changes could be directly attributed to the FMT program., Methods: We performed a retrospective analysis of characteristics and outcomes of patients hospitalized for SFCDI (430 hospitalizations) at a single center, from January 2009 through December 2016. We performed subgroup analyses of 199 patients with fulminant CDI and 110 patients with refractory SFCDI (no improvement after 5 or more days of maximal anti-CDI antibiotic therapy). We compared CDI-related mortality within 30 days of hospitalization, CDI-related colectomy, length of hospital stay, and readmission to the hospital within 30 days before (2009-2012) vs after (2013-2016) implementation of the inpatient FMT program., Results: CDI-related mortality and colectomy were lower after implementation of the FMT program. Overall, CDI-related mortality was 10.2% before the FMT program was implemented vs 4.4% after (P = .02). For patients with fulminant CDI, CDI-related mortality was 21.3% before the FMT program was implemented vs 9.1% after (P = .015). For patients with refractory SFCDI, CDI-related mortality was 43.2% before the FMT program vs 12.1% after (P < .001). The FMT program significantly reduced CDI-related colectomy in patients with SFCDI (6.8% before vs 2.7% after; P = .041), in patients with fulminant CDI (15.7% before vs 5.5% after; P = .017), and patients with refractory SFCDI (31.8% vs 7.6%; P = .001). The effect of FMT program implementation on CDI-related mortality remained significant for patients with refractory SFCDI after we accounted for the underlying secular trend (odds ratio, 0.09 for level change; P = .023)., Conclusions: An FMT program significantly decreased CDI-related mortality among patients hospitalized with refractory SFCDI., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Recurrent Clostridioides difficile infection (CDI) is a major public health threat. While clinical prediction tools exist, they do not incorporate the newest Infectious Diseases Society of America guidelines., Methods: This was a prospective longitudinal study of patients experiencing their first episode of uncomplicated CDI. Patients were followed from diagnosis through 8 weeks post-completion of their anti-CDI therapy to assess recurrence. Stool was collected at diagnosis and weekly for 8 weeks following treatment. Recurrence was defined as diarrhea as well as a positive stool test by toxin EIA (EIA) for C. difficile. Fisher's exact test for binary variables and Student's t test for continuous variables were performed. Cox regression was performed to assess for predictors of CDI recurrence., Results: Seventy-five patients were enrolled between August 1, 2015, and September 1, 2018. Mean age 58.1 years ± 15.5, 69.3% female, 74.7% were white, 11.3% had baseline irritable bowel syndrome, and 54.7% were actively using PPIs. Over the 8-week follow-up period, 22 patients developed a confirmed CDI recurrence. Univariate predictors of recurrence included treatment with metronidazole (40.9% vs 15.1%, p = 0.03), initially diagnosis by EIA (77.3% vs 43.4%, p = 0.007) and platelet count (206 ± 72.1 vs 270.9 ± 114.8, p = 0.03). A Cox regression model revealed primary diagnosis by EIA (HR 3.39, 95% CI 1.23, 9.31, p = 0.018) and treatment with metronidazole (HR 3.27 95% CI 1.31-8.19, p = 0.01) remain predictors for CDI recurrence., Conclusion: In a large prospective longitudinal cohort of uncomplicated CDI patients, treatment with metronidazole and diagnosis via EIA were the most robust predictors of CDI recurrence.

Background & Aims: Although there are many industry-funded trials of microbe-based therapeutics for Clostridioides (formerly Clostridium) difficile infection (CDI), not all patients are eligible for these trials, due to their strict enrollment criteria. Furthermore, given the widespread availability of fecal microbiota transplantation (FMT) and overwhelming evidence to support its efficacy, patients might refuse enrollment in trials with a placebo group. We analyzed willingness and eligibility of patients with recurrent CDI to participate in randomized controlled trials of microbe-based therapeutic agents., Methods: We performed a retrospective study of 199 patients referred to 4 tertiary referral centers for treatment of CDI from August 1, 2018 through January 31, 2019. We collected data on eligibility for FMT and enrollment in randomized controlled trials., Results: Of 130 patients deemed appropriate for FMT, 98 patients (75%) were ineligible for participation in a randomized controlled trial and 16 patients (17%) were eligible but refused to enroll. Immune compromise and inflammatory bowel diseases were the most common reasons for exclusion from trials., Conclusions: Most patients with CDI who meet the guideline criteria for FMT are ineligible or unwilling to participate in randomized controlled trials of microbe-based therapeutics. Trial populations therefore do not represent the population of patients with CDI., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice., Competing Interests: Competing interests: JRA received grants from, and consulted for, Finch Therapeutics and Merck and Co. GC, GI, FS and LM received grants in the field of faecal microbiota transplantation (FMT) from the Italian Ministry of Health. SPC received fees from Shire, Ferring, Microbiotica, Pfizer and Janssen. MF is consultant to Finch Therapeutics Group and DSMB member for Rebiotix. AH has served as consultant, advisory board member or speaker for AbbVie, Atlantic, Bristol-Myers Squibb, Celltrion, Falk, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire and Takeda; she also serves on the Global Steering Committee for Genentech. ZK is an employee/shareholder at Finch Therapeutics and advisor/consultant at OpenBiome. JK and EJK received research grants from Vedanta Bioscences, Boston, USA. CPK is a clinical site for the PRISM FMT trial conducted by Finch Therapeutics. HS received unrestricted study grants: Danone, Biocodex, Enterome; board membership, consultancy or lecture fees: Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat, BiomX, Biose, Novartis, Takeda; co-funder of Exeliom Biosciences. All the remaining authors have nothing to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Faecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT's efficacy in treating the condition., Design: Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of bsh / bai CD genes involved in bile metabolism. Human data were validated in C. difficile batch cultures and a C57BL/6 mouse model of rCDI., Results: From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent C. difficile germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and bsh / bai CD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered bsh -expressing E. coli and naturally BSH-producing organisms ( Bacteroides ovatus, Collinsella aerofaciens, Bacteroides vulgatus and Blautia obeum ) reduced TCA-mediated C. difficile germination relative to culture supernatant of wild-type (BSH-negative) E. coli. C. difficile total viable counts were ~70% reduced in an rCDI mouse model after administration of E. coli expressing highly active BSH relative to mice administered BSH-negative E. coli (p<0.05)., Conclusion: Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI., Competing Interests: Competing interests: JRA consults for Finch Therapeutics. DK has received research funding from Rebiotix. EOP is a co-founder of Nubiyota and serves on its scientific advisory board. All other authors declared no conflict of interests., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Fecal microbiota transplantation (FMT) is a promising therapy for recurrent Clostridioides difficile infection (CDI). Many patients report altered bowel habits including constipation, bloating, gas and loose stool post-FMT despite resolution of CDI, and the etiology remains unclear., Methods: This was a prospective cohort study of adult patients with recurrent CDI who underwent FMT (1) via colonoscopy with patient-selected donor stool, (2) via colonoscopy from a universal stool bank donor, or (3) via capsules from a universal stool bank. Reassessment occurred 8 weeks post-FMT. Those cured were assessed for gastrointestinal symptoms (bloating, loose stools, constipation). Multivariate logistic regression was performed to assess predictors of post-FMT gastrointestinal symptoms., Results: A total of 150 subjects underwent FMT for recurrent CDI, of which 68.7% (103) were female, mean age was 61.5 years±18.1 and 31 patients (20.7%) had preexisting irritable bowel syndrome. Thirty-six had FMT via colonoscopy with a patient-selected donor, 67 via colonoscopy with stool bank donors, and 47 via FMT capsules from stool bank donors. Among those cured, 41 (31.2%) had gastrointestinal symptoms post-FMT. The factors associated with symptoms included younger age (57.2 vs. 64.1 y, P=0.03), a baseline history of irritable bowel syndrome (36.6% vs. 13.3%, P=0.002) and preexisting inflammatory bowel disease (31.7% vs. 10%, P=0.002). Small bowel exposure to donor stool was not related to symptoms (63.4% vs. 62.2%, P=0.89)., Conclusions: Altered bowel habits are a consequence of CDI and are common after FMT. This study suggests that donor type and FMT delivery modality are not related to the presence of irregular gastrointestinal symptoms after FMT.

Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation-the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients-is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy., Methods: We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT., Results: 51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity., Discussion: To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.

Introduction: The risk of a new Clostridium difficile infection (CDI) after FMT is unknown if non-CDI antibiotics are required. It is uncertain if anti-CDI prophylaxis or probiotics would reduce risk. We therefore aimed to compare the risk of CDI with and without antibiotic exposure and the benefit of concomitant anti-CDI antibiotic or probiotic prophylaxis., Methods: This is a multicenter retrospective study carried out at three large FMT referral centers of patients who underwent FMT for recurrent CDI. Patients were assessed for antibiotic use, as well as concomitant use of prophylactic anti-CDI antibiotics or probiotics. Time to CDI recurrence after FMT was evaluated using the Kaplan-Meier method., Results: A total of 404 patients were included: 63% were females, with a mean age of 61.3 ± 18.8 years. Mean length of post-FMT follow-up was 18.1 ± 11.9 months (range 2.2-45.2). Among the entire cohort 8.1% (n = 33) experienced a CDI recurrence. Overall, 111 patients (27.4%) used a non-CDI antibiotic, of which 16.2% (n = 18) experienced a CDI recurrence. Patients who used non-CDI antibiotics were more likely to develop CDI (HR 8.44, 95% CI 4.21-16.93, p < 0.001). The risk of CDI recurrence was not different between patients who received anti-CDI antibiotic prophylaxis to those who did not (HR = 1.88, 95% CI 0.72-4.86, p = 0.2); however, probiotic prophylaxis was associated with a greater risk of CDI recurrence (HR = 2.65, 95% CI 1.02-6.86, p = 0.045)., Conclusion: Non-CDI antibiotic use was not uncommon after successful FMT and significantly increased the risk of a new episode of CDI. In this study, we found that the prophylactic use of anti-CDI antibiotics or probiotics was not protective.

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States with significant risk of both morbidity and mortality. While antimicrobial therapy forms the basis of treatment, there are several clinical scenarios in which antimicrobial therapy alone is insufficient. Evidence continues to show the safety and efficacy fecal microbiota transplantation (FMT) in recurrent and severe CDI. This review will outline FMT efficacy, safety, and indications and present practical advice for clinicians interested in best practices around delivery of FMT., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI), with cure rates higher than 80%. 1-3 FMT failure is defined as diarrhea and a positive stool laboratory test for C difficile at any point during the 8-week follow-up period after FMT. 4 ., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation (FMT)., Methods: All patients who underwent FMT for recurrent Clostridium difficile infection (CDI) via colonoscopy or sigmoidoscopy between June 2013 and April 2015 and had a minimum of 8-week follow-up post FMT at two tertiary care referral centres were included in the study. Patients were prospectively followed both clinically and with stool assessments for 8 weeks post FMT. Assessments occurred at 1 week and 4 weeks post FMT to assess for failure. Failure was defined as presence of diarrhoeal symptoms and a positive CDI stool test by polymerase chain reaction for toxin gene (PCR) at any time point during the 8-week follow-up period. CDI stool testing using PCR was performed at weeks 1 and 4 post FMT in asymptomatic patients as well., Results: 167 patients were included. Twenty-eight patients (16.7% (28/167)) were FMT failures throughout the 8-week period. At week 1, seven patients had already failed the FMT. Of the remaining 160 patients, 144 were asymptomatic, and among these, 141 were negative for C. difficile toxin gene by PCR. This resulted in an asymptomatic carriage rate of 2.1% (3/144). At week 4, 143 patients had not yet failed FMT. Of these patients 129 patients were asymptomatic and among those, 125 were negative by PCR, resulting in an asymptomatic carriage rate of 3% (3/129)., Conclusions: Asymptomatic carriage after FMT is rare. This suggests that testing for cure after FMT in asymptomatic patients is not necessary., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient. Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT. We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Several studies have suggested worsening in inflammatory bowel disease (IBD) activity following fecal microbiota transplantation (FMT). We aimed to assess the risk of worsening in IBD activity following FMT. An electronic search was conducted using MEDLINE (1946-June 2016), EMBASE (1954-June 2016) and Cochrane Central Register of Controlled Trials (2016). Studies in which FMT was provided to IBD patients for IBD management or (Clostridium difficile infection) CDI treatment were included. The primary outcome was the rate of worsening in IBD activity., Results: Twenty-nine studies with 514 FMT-treated IBD patients were included. Range of follow up was 4 weeks to 3 y. The pooled rate of IBD worsening was 14.9% (95% CI 10-21%). Heterogeneity was detected: I2 D 52.1%, Cochran Q test D 58.1, p D 0.01. A priori subgroup analyses were performed. Although not significant, the pooled rate of worsening in IBD activity following FMT for CDI (22.7% (95% CI: 13-36%)) was higher compared with FMT for IBD (11.1% (95% CI 7-17%)). Rates of worsening in IBD after lower GI FMT delivery revealed a higher rate of worsening in IBD activity (16.5% (95% CI: 11-24%)) compared with upper GI delivery (5.6% (95% CI: 2-16%)). Rates of worsening in high quality studies and randomized controls trials (RCTS) suggested a marginal risk of worsening in IBD activity (4.6%, (95% CI: 1.8-11%). Rates of IBD worsening are overall marginal across high quality RCTS. It is unknown if the FMT itself led to the worsening of IBD in this small fraction or if this represents alternative etiologies.

Background: The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI., Aim: To assess the levels of primary and secondary bile acids associated with CDI and associated microbial changes., Methods: Stool and serum were collected from patients with (i) first CDI (fCDI), (ii) recurrent CDI (rCDI) and (iii) healthy controls. 16S rRNA sequencing and bile salt metabolomics were performed. Random forest regression models were constructed to predict disease status. PICRUSt analyses were used to test for associations between predicted bacterial bile salt hydrolase (BSH) gene abundances and bile acid levels., Results: Sixty patients (20 fCDI, 19 rCDI and 21 controls) were enrolled. Secondary bile acids in stool were significantly elevated in controls compared to rCDI and fCDI (P < 0.0001 and P = 0.0007 respectively). Primary bile acids in stool were significantly elevated in rCDI compared to controls (P < 0.0001) and in rCDI compared to fCDI (P = 0.02). Using random forest regression, we distinguished rCDI and fCDI patients 84.2% of the time using bile acid ratios. Stool deoxycholate to glycoursodeoxycholate ratio was the single best predictor. PICRUSt analyses found significant differences in predicted abundances of bacterial BSH genes in stool samples across the groups., Conclusions: Primary and secondary bile acid composition in stool was different in those with rCDI, fCDI and controls. The ratio of stool deoxycholate to glycoursodeoxycholate was the single best predictor of disease state and may be a potential biomarker for recurrence., Competing Interests: Financial disclosures: no conflicts of interest to report for any authors in regards to the work presented in this manuscript., (© 2016 John Wiley & Sons Ltd.)