Fecal-microbiota transplant boosts ulcerative colitis remission

Last Updated: 2019-01-16

By Will Boggs MD

NEW YORK (Reuters Health) - Anaerobically prepared fecal-microbiota transplantation (FMT) improved remission rates in adults with mild to moderate ulcerative colitis (UC) in a randomized trial.

"This study demonstrates that by modifying the luminal environment with a short course of FMT the disease could be improved," Dr. Samuel P. Costello from The Queen Elizabeth Hospital, in Woodville, Australia, told Reuters Health by email. "In the future, FMT may be a viable therapy for UC if maintenance studies demonstrate a benefit."

Three randomized clinical trials have demonstrated variable efficacy of FMT in active ulcerative colitis using aerobically prepared stool specimens with relatively high treatment intensities.

Dr. Costello and colleagues investigated whether FMT using anaerobically prepared pooled stool specimens with a lower treatment burden would prove effective at inducing remission in their randomized, double-blind clinical trial of 73 patients with mild to moderately active UC.

Patients were randomized to receive either anaerobically prepared pooled donor FMT or autologous FMT via colonoscopy followed by two enemas over seven days. Open-label therapy was offered to autologous FMT patients after week 8, and all but one accepted.

Overall, 35 of 38 patients assigned to donor FMT and 34 of 35 patients assigned to autologous FMT completed the week-8 assessment.

Significantly more patients who received donor FMT (12/38, 32%) than who received autologous FMT (3/35, 9%) achieved steroid-free remission at week 8, the researchers report in January 15 issue of JAMA.

Patients receiving donor FMT also had significantly higher clinical-response rates (55% vs. 23% for autologous FMT), clinical-remission rates (47% vs. 17%) and steroid-free endoscopic remission rates (11% vs. 0%).

At 12 months, 11 of 26 patients (42%) originally randomized to the donor FMT group remained in clinical and endoscopic remission.

Most patients who underwent FMT (95%) thought that one-week induction therapy with donor FMT would be acceptable to other patients with UC.

Microbial diversity increased following donor FMT, compared with autologous FMT, at weeks 4 and 8, but microbial diversity and change in diversity at week 8 were not significantly associated with changes in total Mayo scores.

Increased abundance of Anaerofilum pentosovorans and Bacteroides coprophilus species following donor FMT was strongly associated with disease improvement.

Serious adverse events in the donor-FMT group included one case of worsening colitis, one case of C. difficile colitis requiring colectomy and one case of pneumonia. In the control group, there were two cases of worsening colitis.

"FMT can induce remission in ulcerative colitis; however, we do not yet have data on the efficacy of FMT as a maintenance agent," Dr. Costello said. "As such, further trials are required to determine if FMT can maintain remission in UC and also the long-term safety of this therapy for UC. We are about to undertake such a study at the Queen Elizabeth Hospital in Adelaide."

"Our long-term aim is to develop rationally designed microbial therapeutic that can replace FMT," he said. "These will have bacteria that can carry out the therapeutic effect without the need to take whole feces. FMT studies are useful to be able to identify candidate organisms that could then be harnessed for such a therapy. At present, FMT for ulcerative colitis should be given in the clinical-trial setting so that we can determine if it is a viable long-term maintenance therapy."

Dr. Colleen R. Kelly from Warren Alpert Medical School of Brown University, in Providence, Rhode Island, who co-authored a linked editorial, told Reuters Health by email, "We have known for a long time that the gut microbiome plays an important role in the pathophysiology of inflammatory bowel disease. This study suggests that manipulation of the microbiome may be beneficial for a subset of patients with inflammatory bowel disease (IBD)."

"I think it is interesting that this less-intensive FMT regimen (3 doses over 7 days) was just as effective at inducing remission as the previous study which utilized a more intensive FMT regimen (roughly 40 FMTs over 8 weeks)," she said.

Dr. Kelly added, "I predict that in the near future, microbiota-based therapies will be utilized in IBD. I suspect patients will need maintenance dosing at regular intervals, just as we do currently with biologics, and that these therapies targeting the microbiome will probably be used in combination with more traditional immunosuppressants for IBD."

Dr. Ari Grinspan from Icahn School of Medicine at Mount Sinai, in New York City, who recently found FMT to be beneficial for recurrent C. difficile infection in pediatric IBD, told Reuters Health by email, "This is the 4th randomized controlled trial of FMT in active UC. All 4 studies are different (dosing, delivery, donor pools) and therefore difficult to pool together for a cohesive picture of FMT in UC. While very promising, there are still a lot of questions that need answers."

"While the authors provide some analysis of changes in microbiome, metabolome, and immune markers and do find an association between several bacterial species and disease improvement, we are still searching for the mechanism of action of FMT in UC," he said. "What makes a good donor? What makes a good recipient?"

"We need more data on long-term efficacy and safety," Dr. Grinspan said. "Perhaps most importantly, we need a more defined regulatory pathway for a product like FMT to be approved for use by the FDA."

SOURCE: https://bit.ly/2FvbUz6 and https://bit.ly/2FHbiG7

JAMA 2019.