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 multidonor 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.

Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials

“…They further analyzed the effect of oral FMT on abdominal pain, stool frequency, and stool form, but found no clinical beneficial effect ( 25 ). In their following study, they found long-term increased anaerobic bacteria in the FMT group, such as Faecalibacterium, Prevotella , and Bacteroides ( 26 ). It is presumed that the changes in the microbiota induced by oral FMT are not significant enough to improve the IBS symptoms.…”

Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases

“…A specific selection of a donor who shows enrichment in those bacteria lacking in the recipient ( Lachnospiraceae and Ruminococcaceae ) might represent a good strategy, as exploited in clinical trials on hepatic encephalopathy [ 38 , 137 ]., Moreover, the level of engraftment and long-lasting effect represents the main variables in the successful FMT and clinical outcomes. For example, in IBS the post-FMT engraftment of strictly anaerobic bacteria after FMT does not improve symptoms [ 255 ], while post-FMT engraftment in people with chronic constipation is highly populated by species belonging to the Firmicutes and carries genes related to polysaccharide metabolism [ 256 ]. Certainly, the way of FMT delivery, as well as the number of FMT treatments (for example, one single FMT via colonoscopy is not clinically effective in ulcerative colitis [ 78 ]), might play a role as well, but it has become clear that certain donor’s microbiota profiles are more likely to get a better chance to engraft, colonize and to produce a beneficial effect in the host.…”

Intestinal bacteria associated with irritable bowel syndrome and chronic fatigue

“…In the absence of an effective method to restore the dysbiosis, transplanting a microbiome from healthy individuals with well‐functioning guts to those with IBS and dysbiosis (fecal microbiota transplantation [FMT]) is conceivable. In contrast to probiotics treatment, FMT has been found to induce long‐term bacteria colonization in the intestine 18 . FMT has been applied to patients with IBS in seven randomized controlled trials (RCTs), four of which found a positive effect while the other three found no effect 19 .…”

“…In contrast to probiotics treatment, FMT has been found to induce long-term bacteria colonization in the intestine. 18 FMT has been applied to patients with IBS in seven randomized controlled trials (RCTs), four of which found a positive effect while the other three found no effect. 19 It is difficult to compare these RCTs due to variations in the criteria used to select the donors and patients, in the fecal transplant dose used in the FMT, the way the transplant was preserved and prepared, and the administration route.…”