IDDF2023-ABS-0092 Multi-cohort retrospective microbiota analysis on fecal microbiota transplantation in ulcerative colitis

Background

Fecal microbiota transplantation (FMT) has recently been applied to the treatment of ulcerative colitis (UC). However, clinical studies have reported inconsistent results in changes in gut communities after FMT, which need to be further explored with uniform analysis procedures and multi-cohort datasets.

Methods

We searched public databases and collected 1163 fecal samples with 16S rRNA gene sequencing data from patients before and after FMT from 9 studies worldwide. Raw sequences were trimmed and analyzed with a uniform pipeline. Random-effects (RE) and fixed-effects (FE) models were used to explore the change summary estimates in alpha-diversity, beta-diversity, as well as important individual bacterial taxa.

Results

After strict quality control, a total of 185 samples (97 collected from patients with UC before FMT and 88 collected at 4 weeks after FMT) from 5 studies were retained for downstream analysis. Gut bacterial a-diversity indexes of UC, including richness (Observed, Chao1, ACE), Shannon and evenness were significantly improved at 4 weeks after FMT based on RE and FE models (IDDF2023-ABS-0092 Figure 1. Changes in a-diversity and individual gut bacterial taxa of patients with UC after FMT, analyzed by random-effects (RE) and fixed-effects (FE) models (A) Forest plots of the alpha-diversity metrics). We found 40 bacterial genera uniformly changed after FMT, of which 34 (eg. Faecalibacterium, Butyricimonas, Megamonas) significantly increased in post-FMT samples, and 6 significantly decreased (eg. Escherichia_Shigella) (IDDF2023-ABS-0092 Figure 1. Changes in a-diversity and individual gut bacterial taxa of patients with UC after FMT, analyzed by random-effects (RE) and fixed-effects (FE) models (B) Genera with significant ORs between pre-FMT and post-FMT). Similarly, we found 19 characteristic bacteria species, of which 18 showed a significant increase (eg. Prevotella_copri, Alistips_shahii). Moreover, we further grouped the samples according to the therapeutic effects (response, RP vs. non-response, NR), and explored the changes in the relative abundance of these characteristic bacteria before and after FMT. Interestingly, Alistipes and NK4A214_group were uniquely increased in the RP group after FMT, while [Ruminococcus]_gnavus_group and Erysipelatoclostridium were specifically decreased in the RP group and increased in the NR group (IDDF2023-ABS-0092 Figure 1. Changes in a-diversity and individual gut bacterial taxa of patients with UC after FMT, analyzed by random-effects (RE) and fixed-effects (FE) models (C) Genera with distinct changing trends between RP group and NR group after FMT). These characteristic bacteria may be the key taxa contributing to the curative effect of FMT in UC.

Conclusions

We uniformly analyzed existing samples from 5 clinical studies, and found gut bacterial a-diversity indexes were significantly improved after FMT. Bacteria important for the therapeutic effects were further identified at genus and species levels. These results help better understand the role of gut microbiota in the treatment of UC and the development of live biotherapeutic products.