Alteration of Intestinal Dysbiosis by Fecal Microbiota Transplantation Does not Induce Remission in Patients with Chronic Active Ulcerative Colitis

TLDR

Dysbiosis is thought to contribute to ulcerative colitis inflammation, and fecal microbiota transplantation has proven effective for recurrent Clostridium difficile colitis. This study aimed to determine whether fecal microbiota transplantation benefits patients with chronic active ulcerative colitis and reverses dysbiosis. Six refractory UC patients received a single colonoscopic donor stool infusion, and changes in colonic microbiota were monitored by high‑throughput 16S rDNA sequencing, revealing short‑term clinical improvement within two weeks. Despite transient improvement, none of the patients achieved remission, microbiota shifts varied among individuals, and donor‑like microbiota changes did not correlate with clinical response, suggesting dysbiosis is a secondary effect of inflammation rather than a primary driver.

Abstract

In patients with ulcerative colitis (UC), alterations of the intestinal microbiota, termed dysbiosis, have been postulated to contribute to intestinal inflammation. Fecal microbiota transplantation (FMT) has been used as effective therapy for recurrent Clostridium difficile colitis also caused by dysbiosis. The aims of the present study were to investigate if patients with UC benefit from FMT and if dysbiosis can be reversed.Six patients with chronic active UC nonresponsive to standard medical therapy were treated with FMT by colonoscopic administration. Changes in the colonic microbiota were assessed by 16S rDNA-based microbial community profiling using high-throughput pyrosequencing from mucosal and stool samples.All patients experienced short-term clinical improvement within the first 2 weeks after FMT. However, none of the patients achieved clinical remission. Microbiota profiling showed differences in the modification of the intestinal microbiota between individual patients after FMT. In 3 patients, the colonic microbiota changed toward the donor microbiota; however, this did not correlate with clinical response. On phylum level, there was a significant reduction of Proteobacteria and an increase in Bacteroidetes after FMT.FMT by a single colonoscopic donor stool application is not effective in inducing remission in chronic active therapy-refractory UC. Changes in the composition of the intestinal microbiota were significant and resulted in a partial improvement of UC-associated dysbiosis. The results suggest that dysbiosis in UC is at least in part a secondary phenomenon induced by inflammation and diarrhea rather than being causative for inflammation in this disease.