Credit: istock.com/SolStock
Colonic delivery of fecal microbiota transplantation (FMT) was a more effective route than nasogastric administration for patients with ulcerative colitis (UC), according to results from the STOP-Colitis trial.
Additionally, “delivery by the colonic route was much more acceptable for patients compared to delivery via nasogastric tubes,” reported study author Tariq H. Iqbal, MD, of the University of Birmingham Microbiome Treatment Centre, University of Birmingham, UK.
Previous research has shown that FMT for UC is a promising strategy “to correct dysbiosis by restoring microbial diversity and composition and potentially re-establishing immune balance.” However, studies in this patient population have varied widely in different methods of FMT preparation, donor selection, and delivery methods.
In STOP-Colitis, Dr. Iqbal and colleagues sought to compare two available FMT delivery routes. They conducted an open-label, prospective pilot trial that enrolled 30 adults with active UC and randomly assigned them to receive multidose FMT via either nasogastric tube or colonoscopy with subsequent enemas.
Nasogastric delivery consisted of four daily 50 mL infusions of FMT via nasogastric tube at baseline and again at week 4. Colonic delivery consisted of a single 250 mL FMT administration at baseline followed by seven weekly 100 mL self-administered enemas.
Delivery via colonoscopy yielded a higher clinical response rate (RR) at week 8, a key end point, as compared with nasogastric delivery (75% vs 25%; RR=2.94; 95% CI, 0.84-10.30). The rate of clinical remission was also higher in the colonic arm (6 out of 12 vs 2 out of 8). The mucosal healing rate was 25% in both study arms. Weight and quality of life scores at weeks 8 and 12 were similar among participants in each study arm.
There were significant shifts in microbiome composition across all recipients of FMT. Among the responders, there were significant increases in the abundance of 24 species, including from the phylum Firmicutes and family Oscillospiraceae. Additionally, “the presence of specific species at day 56, such as Firmicutes t__SGB15368 (absent at day 1), indicated microbial engraftment unique to responders,” the researchers wrote.
“Response was associated with reduction in Th17 cells (pro-inflammatory) and an increase in gut-homing T regs (anti-inflammatory) in the colonic mucosa,” Dr. Iqbal said.
Adverse events (AEs) occurred in the majority of patients whether assigned to the colonic (79%) or nasogastric (69%) delivery. In the nasogastric arm, the most common AEs were abdominal pain and nausea; in the colonic arm, diarrhea and abdominal pain. Two serious AEs were reported in the nasogastric arm, but none were reported with colonic delivery.
Limitations to this study included its relatively small cohort size, which restricted its generalizability, and its short follow-up duration. In addition, Dr. Iqbal noted that the study was not powered for efficacy.
“This study builds on evidence that microbial manipulation is effective in treating ulcerative colitis,” Dr. Iqbal said. “Future work should aim to refine the microbiome actors which are important in this action with a view to developing rational live biotherapeutics and establishing microbial treatments in our treatment algorithms for IBD.”
Dr. Iqbal and colleagues are about to initiate a new FMT study in patients with newly diagnosed UC.