Fecal microbiota transplants (FMTs) have been explored for several years as a potential solution to treat patients suffering from prolonged and intractable abdominal distress due to inflammatory conditions like irritable bowel syndrome (IBS). Despite some encouraging results, the long-term effectiveness of FMT as a therapy, as well as the adverse effects of this procedure, remain unclear.
A new Gastroenterology journal study by researchers in Norway discusses the efficacy of FMTs in patients with IBS three years after the procedure was performed.
The gut microbiome varies significantly in its composition and abundance between different people. In fact, over the past several decades, researchers have reported the contribution of the microbiome to various conditions ranging from autism spectrum disorders (ASD) to IBS.
The differences in gut microbiome quality following FMT have been experimentally studied and adjusted in several randomized controlled trials (RCTs). While four of these studies reported positive findings, the other three failed to identify any evidence of improved quality of life. These discrepancies might be attributable to variations in the experimental design, including the donors and patients selected, the dose of fecal microbiota used for the transplant, and the route of administration.
About the Study
The current study was a three-year follow-up of post-transplant patients with IBS and included an analysis of their fecal samples and questions about their quality of life.
A total of 125 patients were included at the three-year mark, 38 of whom were treated with placebo, whereas 42 and 45 patients received 30 g and 60 g of donor feces, respectively. All transplanted fecal specimens exhibited a high level of microbial diversity and originated from a single 36-year-old healthy male unrelated to any recipient in this study. The donor also maintained a healthy gut microbial diversity throughout the follow-up period with a stable composition.
Ten patients required a repeat FMT with 90 g donor feces due to relapse at three years from their FMT.
Symptoms were then assessed using IBS Severity Scoring System (IBS-SSS) and the Birmingham IBS Symptom Questionnaire, while fatigue was measured with the Fatigue Assessment Scale (FAS) questionnaire. A reduction in post-FMT IBS-SSS score by 50 or more points was considered a positive response, while a decrease of 75 points or more was considered complete remission.
Quality of life was considered to be improved if there was an increase in the IBS Quality of Life (IBS-QOL) score and a decrease in the Short-Form Nepean Dyspepsia Index (SF-NDI) score. The fecal bacteria composition was also assessed using the GA-map® Dysbiosis Test.
Excluding dropouts and a single patient who did not meet the inclusion criteria, recipients who received FMT had higher response rates as compared to placebo recipients at two and three years from the transplant.
Both 30 g and 60 g recipients reported reduced symptom severity and fatigue as compared to the placebo group two and three years after their transplant. These patients also reported less abdominal pain, distension and troubling bowel habits, as well as less interference with their quality of life.
The dysbiosis index was decreased in both groups of recipients, thus showing a positive association with the other symptom scores. The proportion of dysbiotic patients significantly declined in all groups at two and three years from FMT; however, no significant differences were observed between responders and non-responders.
The fecal microbial profile, which was similar at baseline in all three groups, changed significantly over the three-year period. Over 25 bacterial species showed increases or decreases at two and three years from FMT.
Of the bacterial species that changed only in the recipient groups but not the placebo group, nine were associated with the total IBS-SSS scores, of which six and three were positively and negatively associated, respectively. Seven bacterial species were negatively associated with the FAS scores, whereas three were positively associated with these scores.
Severity-Based Difference in Response
Patients with severe IBS symptoms improved to a greater extent than those with moderate IBS in both FMT groups, while the proportion remained unchanged in the placebo group. About 75% of severe IBS patients responded to FMT with a significant reduction in symptoms as compared to over 50% of patients with moderate IBS symptoms.
The initial scores on the IBS-QOL and SF-NDI were higher at baseline in those with severe IBS. This difference eventually declined, as did the difference in IBS symptom severity, at two and three years post-FMT. Patients with severe IBS reported more significant improvements in their quality of life at both time points relative to their baseline scores such that their final scores were comparable for severe and moderate IBS patients.
Dysbiosis also improved to a greater extent in severe IBS patients at both time points as compared to patients with moderate IBS, though both groups showed similar dysbiosis severity at baseline. Severe IBS differed from moderate IBS in several bacterial markers, such as Clostridia and Lactobacillus, which was higher in the moderate IBS group, and Firmicutes or Eubacterium siraeum, which was higher in the severe IBS group.
Bacterial diversity indicators and symptom severity were similar between the sexes, while four and five bacterial species showed significant differences between males and females at two and three years from FMT, respectively. Females tended to respond better than males at both time points; however, the rates of complete remission were similar in both sexes.
The highest response rates were observed in those with predominant diarrheal or mixed diarrhea-constipation types of IBS as compared to predominant constipation-type IBS at two years, but not three years following their transplant. Complete remission rates were similar in all three subtypes of IBS. Furthermore, microbial markers and symptom scores did not show any marked differences between these subtypes of IBS at any time point.
The response rate to retransplantation was 80% at three months post-FMT with lower symptom scores. However, there was no major change in the quality of life. Dysbiosis also improved significantly after retransplantation.
In the current study, FMT was associated with a sustained benefit for up to three years after the procedure was performed. More specifically, abdominal symptoms and fatigue improved with a corresponding increase in the quality of life. Furthermore, the proportion of severe IBS was significantly lower at two and three years following the FMT.
Among those who relapsed within three years, FMT retransplantation provided a beneficial effect, thus indicating that this mode of treatment is both durable and efficacious in its response rates. The researchers linked this to the donor selection criteria that were based on bacterial species which positively affect the gut microbiota in terms of abundance, diversity, and stability over time, as well as the use of precautions to preserve bacterial viability and growth.
The extent of dysbiosis, rather than its presence or absence, is extremely important to IBS, as dysbiosis was more severe in the placebo group when compared to either FMT group at the end of the follow-up period. All groups reported similar dysbiosis at the beginning of the study.
The current study also emphasizes the potential importance of ten bacterial species in IBS symptom scores, with more than half of these species showing higher signals in responders. These species have been associated with several physical-mental conditions including ASD, depression, chronic fatigue syndrome, and aging, as well as butyric acid production. Butyric acid is a short-chain fatty acid (SCFA) that is known for its role as an energy supplier to the colonic mucosa, immunomodulator, and guard of the intestinal epithelial barrier.
Further research will help elucidate the differential impact of FMT on both male and female IBS patients. As a recent study showed, females typically report a better response than males to FMT, both early on and after three years, as do those with severe IBS as compared to those with moderate IBS three years following their transplant.
Notably, the current study provided evidence regarding the safety of FMT over the medium-term in otherwise healthy patients.