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

ABSTRACT: 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.

SUBMITTER: Browne PD

PROVIDER: S-EPMC8183560 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS. METHODS:We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement. RESULTS:Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met eligibility. No significant difference in global improvement of IBS symptoms was observed at 12 weeks in FMT vs placebo (RR = 0.93; 95% CI 0.48-1.79). Heterogeneity among studies was significant (I = 79%). Subgroup analyses revealed benefits of single-dose FMT using colonoscopy and nasojejunal tubes in comparison with autologous FMT for placebo treatment (number needed to treat = 5, RR = 1.59; 95% CI 1.06-2.39; I = 0%) and a reduction in likelihood of improvement of multiple-dose capsule FMT RCTs (number needed to harm = 3, RR = 0.54; 95% CI 0.34-0.85; I = 13%). Placebo response was 33.7% in nonoral FMT RCTs and 67.8% in capsule FMT RCTs. The Grading of Recommendations Assessment, Development and Evaluation quality of the body of evidence was very low. DISCUSSION:Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms. There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.

Project description:BackgroundThe intestinal microbiota is thought to be involved in the occurrence of inflammatory bowel disease in remission with irritable bowel syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. This cross-sectional study aims to investigate the fecal microbiota profiling in patients with these diseases.MethodsFecal samples from 97 subjects, including Crohn's disease patients in remission with IBS-type symptoms (CDR-IBS+) or without IBS-type symptoms (CDR-IBS-), ulcerative colitis patients in remission with IBS-type symptoms (UCR-IBS+) or without IBS-type symptoms (UCR-IBS-), IBS patients and healthy controls, were collected and applied 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified and sequenced by the Illumina MiSeq platform. The differences in the sample diversity index in groups were analyzed with R software.ResultsThe richness of the intestinal microbiota in the CDR-IBS group was markedly lower than those in the control and IBS groups based on the analysis of observed species and the Chao index (P < 0.05). The observed species index in the CDR-IBS+ group was higher than that in the CDR-IBS- group (median index: 254.8 vs 203, P = 0.036). No difference was found in alpha diversity between UCR patients with IBS-type symptoms and those without related symptoms. At the genus level, the number of Faecalibacterium in CDR patients with IBS-type symptoms increased significantly, while Fusobacterium decreased versus those without such symptoms (mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P < 0.05; Fusobacterium: 1.51% vs 5.2%, P < 0.05). However, compared with the UCR-IBS- group, the number of Faecalibacterium in the UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no significant difference in the genus structure. The abundance and composition of the microbiota of IBS patients were not distinct from those of healthy controls.ConclusionsThe IBS-type symptoms in CD patients in remission may be related to an increase in Faecalibacterium and a decrease in Fusobacterium. The IBS-type symptoms in UC patients in remission cannot be explained by changes in the abundance and structure of the intestinal microbiota.

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

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