Successful treatment of Clostridioidesdifficile infection with single-donorfaecal microbiota transplantation capsules.

INTRODUCTION: Treatment of recurrent Clostridioides difficile infection with faecal microbiota transplantation (FMT) is highly effective and is the recommended treatment following a second recurrence. The cure rates of capsule treatment are high (82%-88%). Whether using multi-donor or single-donor FMT capsules affects cure rates remains incompletely understood. METHODS: A retrospective case series of patients with recurrent, refractory or fulminant C. difficile infection treated for three days with single-donor FMT capsules from October to December 2020 was conducted. The aim of the study was to investigate the clinical efficacy (cure rate) of the treatment and to compare cure rates with previously reported cure rates of treatment with multi-donor FMT capsules produced at the same stool bank. Clinical cure was defined as absence of diarrhoea or diarrhoea with a C. difficile negative stool sample eight weeks after treatment. RESULTS: Clinical cure was observed in 15 of the 18 (83.3%) patients following three days of FMT capsule treatment. Cure rates were comparable (p = 1.0) to previously reported cure rates (88.9%) of multi-donor FMT capsule treatment of recurrent C. difficile infection. CONCLUSIONS: Three days of single-donor FMT capsule treatment was effective and safe in the treatment of recurrent, refractory and fulminant C. difficile infection with cure rates comparable to those of multi-donor FMT capsule treatment. FUNDING: This work was supported by the Danish Innovation Fund under Grant 7076-00129B, MICROHEALTH. The funders had no role in the study design, data collection or analysis, the decision to publish, or in the preparation of the manuscript. The FMT capsules from the Aleris-Hamlet FMT Stool Bank were supplied to the Copenhagen University Hospital - Hvidovre Hospital free of charge. TRIAL REGISTRATION: not relevant.

Engraftment of strictly anaerobic oxygen-sensitive bacteria in irritable bowel syndrome patients following fecal microbiota transplantation does not improve symptoms.

Dysbiosis of the gut microbiome has been correlated with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is being explored as a therapeutic option. Little is known of the mechanisms of engraftment of microbes following FMT and whether the engraftment of certain microbes correlate with clinical improvement in IBS. Microbiome data, from a previously reported placebo-controlled trial of treatment of IBS with FMT or placebo capsules, were used to investigate microbial engraftment 15 days, 1, 3 and 6 months after treatment through assessment of gains, losses and changes in abundance of amplicon sequence variants (ASVs) and microbial diversity (CHAO-1 richness) between the FMT group and the placebo group. These data were compared to changes in IBS Symptom Severity Scores (IBS-SSS). Twelve days of treatment with 25 daily multi-donor FMT capsules induced significant short- and long-term changes in the recipients' microbiomes for at least 6 months, with persistent engraftment of a variety of anaerobic bacteria from keystone genera, such as Faecalibacterium, Prevotella and Bacteroides and increased microbial diversity, particularly in patients with low initial diversity. FMT recipients lost ASVs after treatment, which was seen to a much lesser extent in the placebo group. No ASVs increased to a greater extent between FMT responders and non-responders following treatment. Major long-term changes, lasting for at least 6 months, in the gut microbiomes of IBS patients are seen following treatment with FMT capsules. None of these changes correlated with clinical improvement. The relationship between the microbiome and the etiology of IBS still remains unsolved.

The effect of faecal microbiota transplantation on abdominal pain, stool frequency, and stool form in patients with moderate-to-severe irritable bowel syndrome: results from a randomised, double-blind, placebo-controlled study.

BACKGROUND: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis. Therefore, faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. In this study, we analysed previously unexamined data from our randomised, double-blind, placebo-controlled study (trial registration number NCT02788071). The objective was to evaluate the effect of FMT on abdominal pain, stool frequency, and stool form. METHOD: The study included 52 adult patients with moderate-to-severe IBS assigned randomly to treatment with FMT capsules or placebo capsules (1:1) for 12 days. The patients were followed for a total of six months, during which they kept a daily symptom diary tracking their abdominal pain on a scale from 0-10 and their bowel movements using the Bristol Stool Form Scale (BSFS). Diary data were not collected before treatment start. RESULTS: A statistically significant improvement in stool frequency was found in the FMT group from during treatment to post-treatment and 1 month. No statistically significant differences were found between groups at any time during the study for any of abdominal pain, stool frequency, and stool form (as measured by weighted stool score). CONCLUSION: In this analysis of results from a randomised, double-blind, placebo-controlled study, we found no clinically beneficial effect of FMT on abdominal pain, stool frequency, or stool form. However, since the current literature on the potential role of FMT in treating IBS shows conflicting results, further studies are required. To assess treatment efficacy, we recommend future studies to include daily symptom diaries both before and after treatment intervention.

Case series of successful treatment with fecal microbiota transplant (FMT) oral capsules mixed from multiple donors even in patients previously treated with FMT enemas for recurrent Clostridium difficile infection.

RATIONALE: Studies have shown that fecal microbiota transplantation (FMT) is a safe and highly efficient treatment for recurrent Clostridium difficile infection (rCDI). However, it is still unknown if one versus multiple donors or enemas versus capsule FMT are most efficient. PATIENT CONCERNS: 10 patients with at least 3 previous episodes of CDI were offered treatment with FMT capsules. 9 patients decided to participate. DIAGNOSES: In this study, we treated 9 patients (25-86 years) with rCDI. INTERVENTIONS: From October to November 2016, a total of 9 patients with recurrent CDI were treated with oral fecal microbiota capsules, with mixed donor feces from 4 donors with high microbiota diversity. All patients received treatment with vancomycin prior to the capsule regime. OUTCOME: Patients had previous recurrences ranging from 2 to 10 recurrences. All 9 patients were successfully treated without recurrence after 180 days follow-up, even 2 patients previously treated with FMT enemas. LESSONS: FMT capsules based on multiple donors are highly efficient in patients with rCDI.

Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study.

OBJECTIVE: IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS. DESIGN: We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected. RESULTS: A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not. CONCLUSION: In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS. TRIAL REGISTRATION NUMBER: NCT02788071.

[Gut microbiota and depressive symptoms].

The gut microbiota is believed to affect a wide variety of mental disorders, including depression. The hypothesis involves bacterial signalling to the host through metabolic, endocrinal, immunologic and neuronal pathways. Few studies of patients with depression have shown altered microbiota profiles and increased levels of systemic endotoxin, which can be detected by leucocytes and result in expression of cytokines. Studies performed so far have lacked statistical power and provide no causal explanation for the gut-brain hypothesis. Further research into the matter is certainly warranted.

Can fecal microbiota transplantation cure irritable bowel syndrome?

AIM: To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS). METHODS: We searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed literature was based on two systematic searches in each of the databases. The MeSH terms used were IBS and fecal microbiota transplantation and the abbreviations IBS and FMT. Reference lists from the articles were reviewed to identify additional pertinent articles. RESULTS: A total of six conference abstracts, one case report, one letter to the editor, and one clinical review were included. In the final analysis, treatment of 48 patients was evaluated. Treatment revealed an improvement in 58% of cases. The varying structure of the nine included studies must be taken into consideration. CONCLUSION: Data on FMT and IBS are too limited to draw sufficient conclusions. Standardized double blinded randomized clinical trials need to be carried out to evaluate the effect of FMT on IBS.