Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study

Abstract

ObjectiveFaecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings.DesignThis randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a reduction in the IBS symptoms at 3 months after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a reduction in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analysed by 16S rRNA gene sequencing, at 1 month following FMT.ResultsResponses occurred in 23.6%, 76.9% (p<0.0001) and 89.1% (p<00.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, respectively. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms.ConclusionsFMT is an effective treatment for patients with IBS. Utilising a well-defined donor with a normal DI and favourable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose.Trial registrationwww.clinicaltrials.gov (NCT03822299) and www.cristin.no (ID657402).

Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome

“…Thus, the transplanted microbiota seemed to engraft successfully in the patients. This observation is in line with and extends the previous studies which showed successful engraftment of donor´s microbiota in IBS patients for up to 6 months with FMT capsules, 18 for 2 months with a single FMT administered via colonoscopy 19 and for 3 months with FMT administered via gastroscopy 21 . Thus, FMT seems to change the microbiota composition in IBS subjects relatively permanently, a phenomenon which has also been observed in FMT‐treated rCDI patients 15 .…”

“…We recruited 55 patients and aimed to include minimum of 52 patients based on the power calculation, but finally excluded six due to exclusion criteria and thus 49 patients were left for final analysis. The previously published placebo‐controlled trials of FMT in IBS have had patient sizes ranging from 17 to 165 17‐21 . Furthermore, we allowed patients with any IBS subtype or any grade of severity to participate in the study, in comparison to the study of Johnsen et al in which constipation predominant IBS patients were excluded 17 .…”

“…In summary, FMT via colonoscopy resulted in a modest, but transient, decrease in IBS symptoms, 17,19 the FMT capsules did not exert any benefits 18,20 but FMT via gastroscopy achieved a clear benefit with an up to 89.1% response rate 21 . Although all these three administration routes, that is capsules taken orally for 12 days or a single FMT via colonoscopy or gastroscopy, altered the microbiota of IBS patients towards that of the donor, 18 a concurrent decrease in the symptoms was observed only when FMT was administered via colonoscopy 19 or gastroscopy 21 . Given the mixed results, the efficacy of FMT in IBS seems to depend not only on the microbiota of the donor, but perhaps also on some other element of the stool, or on the survival of key elements of the microbiota while the stool is processed.…”

Marshall and Warren Lecture 2019: A paradigm shift in pathophysiological basis of irritable bowel syndrome and its implication on treatment

“…Of the three randomized controlled trials on fecal transplantation in IBS published till data, the study from Denmark showed lack of improvement in IBS symptoms despite a change in fecal microbiota 71 though the two studies from Norway showed significant relief in IBS symptoms during short‐term follow‐up following the therapy. One of the two Norwegian studies showed that donor's fecal microbiota and the fecal microbiota doses were the key to the success 72, 73 . The Denmark study might have limitation, as it included patients with IBS‐C as well and used oral route of fecal transplantation with a potential risk of development of SIBO exacerbating IBS symptom, though one of the two Norwegian studies also had these limitations yet gave a positive result 73 .…”

“…One of the two Norwegian studies showed that donor's fecal microbiota and the fecal microbiota doses were the key to the success 72, 73 . The Denmark study might have limitation, as it included patients with IBS‐C as well and used oral route of fecal transplantation with a potential risk of development of SIBO exacerbating IBS symptom, though one of the two Norwegian studies also had these limitations yet gave a positive result 73 . More adequately powered long‐term follow‐up studies on fecal transplantation on well‐characterized patients with different subtypes of IBS are needed.…”