Spotlight on long-term effects of FMT

Two recent studies examined the long-term safety and efficacy of fecal microbiota transplantation (FMT) for GI diseases.

The first study found that most trial participants who received FMT for irritable bowel syndrome (IBS) maintained their response at three years after transplantation. The Norwegian trial included 125 patients (83.2% female), 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. Participants provided a fecal sample and completed five questionnaires at baseline and at two and three years after FMT. The primary end point was a reduction in the IBS Severity Scoring System (IBS-SSS) total score of 50 points or greater at three months after FMT. Results were published online on June 13 by Gastroenterology.

Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at two years after FMT and 27.0%, 64.9%, and 71.8%, respectively, three years after transplantation. The total IBS-SSS scores in the 30-g and 60-g groups were significantly lower than those in the placebo group at both two and three years after FMT. The scores for the four items in the IBS-SSS (abdominal pain, abdominal distension, dissatisfaction with bowel habits, and quality-of-life interference) were also significantly reduced compared with the placebo group at two and three years after FMT. While mild intermittent abdominal pain, diarrhea, and constipation were reported within the first two days after FMT, no other adverse events were reported during follow-up. The study included three IBS subtypes (IBS with diarrhea, IBS with constipation, and IBS with mixed bowel habits) but not unsubtyped IBS, among other limitations, the authors noted. “The present finding that the FMT-treated IBS patients had no further adverse events after a 3-year follow-up period indicates that FMT is a safe intervention,” they wrote. “However, it should be remembered that the patients included in this study did not have a systemic disease or immune deficiency.”

The second study found that FMT for GI symptoms appears safe at both short-term and long-term follow-up. Researchers retrospectively analyzed 8,547 patients who underwent FMT at an academic hospital in China between Jan. 1, 2012, and Sept. 30, 2021. They included patients with various GI diseases or extraintestinal diseases that involved intestinal dysfunction, with the most common indication being functional constipation (an approved indication according to Chinese clinical practice guidelines for FMT). Patients received a questionnaire assessing demographic information, adverse events related to FMT, and newly diagnosed diseases or symptoms during follow-up at two weeks, three months, one year, and five years after FMT. Results were published online on June 13 as correspondence in The Lancet Gastroenterology & Hepatology.

Survey response rates dropped over time, ranging from 95.2% at two weeks to 41.9% at five years. Overall, the most frequently reported adverse events were mild or moderate in severity and were transient, although 42 patients had worsening symptoms of digestive system discomfort at two weeks after FMT. At five years after FMT, 248 new diseases or symptoms were reported in 1,034 patients, most commonly GI disorders and respiratory disorders; however, there were no substantial differences in incidence of these new diseases and the nationally published incidence in the general population. There were nine patient deaths at five years, none of which were directly attributed to FMT. In addition, no FMT-related infection transmission was reported during follow-up. The study was subject to possible classification and selection bias and did not include a control population, among other limitations, the authors noted. “Overall, FMT appears safe at both short-term and long-term follow-up,” they wrote.