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.

Keywords: FMT; Fecal microbiota transplantation; amplicon sequence variants; anaerobic bacteria; bowel cleansing; diversity; dysbiosis; engraftment; gut microbiome; irritable bowel syndrome.

Figure 1.

Change in fecal microbial diversity after FMT and Placebo treatment. Alpha diversity (Chao1) is shown for the donors and treatment groups at baseline and at all post-treatment time-points. Asterisks indicate significant difference from baseline within each treatment group (p < .05). Horizontal lines indicate medians, boxes indicate interquartile ranges and whiskers indicate ranges. FMT, Fecal Microbiota Transplantation

Figure 2.

Change in diversity in patients with initial low and normal diversities. Grey lines represent individual patients and black lines represent average diversity of each group; FMT, Fecal Microbiota Transplantation

Figure 3.

Phylum and genus of bacteria with increased/decreased relative abundance after FMT. The colored areas indicate the proportion of ASVs, among the total number of ASVs either detected (Total ASVs), increased in abundance in FMT patients, or decreased in abundance in FMT patients, assigned to the phyla or genus indicated below. The increase and decrease columns are based on all post-baseline samples from the FMT-treated patients, when compared to placebo treated patients

Figure 4.

Principle coordinate analysis of ASV gains and losses in the FMT and Placebo responders and non-responders

Figure 5.

Proportions of different bacteria/archaea derived from the donors in the FMT patients. In each FMT patient’s sample for the relevant time-point (3 months), the proportions of each ASV attributed to coming from the donors was inferred using sourcetracker2. These proportions were all averaged to get an engraftment score for that node. Similarly, an engraftment score was also calculated for the placebo group. The score associated with the placebo group was used as a floor to rescale score assigned to the FMT group