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

Abstract

Objective: Faecal 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.

Design: This 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.

Results: Responses 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.

Conclusions: FMT 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 registration www.clinicaltrials.gov (NCT03822299) and www.cristin.no (ID657402).

Keywords: colonic microflora; irritable bowel syndrome; lactobacillus.

Figure 1

Consolidated standards of reporting trials) diagram showing the enrolment and randomisation of the patients.

Figure 2

Although the superdonor was normobiotic, his bacterial profile deviated from the expected normal abundance in 14 of the 39 bacteria markers. The deviating bacteria belong to the typical commensal bacteria species that do not contribute to dysbiosis. In all, 12 of these bacteria belong to the phylum Firmicutes (grey), one to the phylum Proteobacteria (light green) and one to the phylum Verrucomicrobia (light blue).

Figure 3

Scaled principal component analysis plot of faecal samples from the superdonor and patients before transplantation. The patient samples are indicated by small grey circles. The superdonor samples are indicated by the larger circles of different colours that indicate the sampling times: Black, 3 months; red, 6 months; green, 9 months; blue, 12 months; light blue, 15 months; and pink, 18 months. All of the superdonor samples are grouped closely together and remain in very similar positions over time.

Figure 4

Responses of patients with IBS to placebo, 30 g FMT and 60 g FMT at different intervals after transplantation. ^**, p<0.001; ^****, p<0.0001 compared with placebo. ^*, p<0.001; ^***, p<0.0001 for 30 g FMT compared with 60 g FMT. IBS, irritable bowel syndrome; FMT, faecal microbiota transplantation.

Figure 5

Scaled PCA plot of faecal samples before and after transplantation for placebo (A), 30 g FMT (B), 60 g FMT (C), responders (D) and non-responders (E). Faecal samples before and after transplantation are indicated by pink circles and blue triangles, respectively. The ellipses cover 80% of the samples within a group. FMT, faecal microbiota transplantation; PCA, principal component analysis.