Antibiotics Plus Oral Fecal Microbiota Transplantation Tied to Ulcerative Colitis Remission

By Marilynn Larkin

December 28, 2021

NEW YORK (Reuters Health) - In patients with active ulcerative colitis (UC), antibiotics followed by oral lyophilized fecal microbiota transplantation (FMT) was associated with induction of remission in a small placebo-controlled trial in Australia.

"We were surprised by the magnitude of improvement with oral FMT, (which) appeared to be independent of the patients' current treatment," Dr. Rupert Leong of Concord Repatriation General Hospital in New South Wales and the University of Sydney told Reuters Health by email.

"Patients not only benefited symptomatically, but at 56 weeks those randomized to continue FMT demonstrated not only endoscopic remission, but histologic remission as well," he said. "Perhaps manipulation of the intestinal microbiome might improve the efficacy of conventional treatments.

His team randomly assigned 35 UC patients (median age, 37; about 50% women overall) to receive oral lyophilized FMT (15 patients) or placebo for eight weeks. All patients first received two weeks of priming oral antibiotics, including amoxicillin, metronidazole, and doxycycline. They were also allowed to continue conventional therapies.

Recruitment was terminated early due to the COVID-19 pandemic, the researchers reported in The Lancet Gastroenterology and Hepatology.

At week 8, 53% in the FMT group had met the primary endpoint -- corticosteroid-free clinical remission with endoscopic remission or response -- as had 15% in the placebo group.

Adverse events were generally mild and occurred in 67% of patients in the FMT group and 85% of those in the placebo group during the 8-week induction period. Serious adverse events included worsening UC (two in the FMT group, one in the placebo group) and large volume per-rectal bleeding due to hemorrhoids (one in the placebo group).

Ten patients in the FMT group with a clinical or endoscopic response entered the maintenance phase and were randomly assigned to continue dose-reduced FMT (four patients) or withdraw from therapy. As Dr. Leong indicated, the four patients who continued FMT were in clinical, endoscopic, and histologic remission at week 56 compared with none of the patients who had FMT withdrawn.

Dr. Leong noted that the Australian Consensus Working Group on FMT was the first published consensus guidelines recognizing FMT as an indication for induction of remission in UC.

"(Our) study demonstrates the potential for ongoing benefit with dose-reduced FMT to maintain FMT in UC," he said, "but an adequately powered study is required to formally determine the magnitude of this benefit."

Dr. Monika Fischer of Indiana University in Indianapolis, coauthor of a related editorial, commented in an email to Reuters Health, "The oral FMT capsules that are stable at 4 degrees C or room temperature will be a paradigm changer in the field of microbiome modulation. It is a crucial step in the march toward development of live biotherapeutic products not only for UC but a large spectrum of diseases believed to have a casual relationship with alteration of the gut microbiota."

"Currently, over 150 ongoing interventional trials in the US alone use FMT, aiming for cure for a variety of gastrointestinal, neuropsychiatric, dermatologic and oncologic illnesses," she said. "I predict that this number will exponentially increase with the availability oral FMT capsules with lyophilized microbiota that solve the logistic issues of repeated dosing as well as product handling and storage."

SOURCE: https://bit.ly/3H4MeVI and https://bit.ly/3myR063 Lancet Gastroenterology and Hepatology, online December 2, 2021.

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