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FMT explored as a potential weight loss treatment



Performing fecal microbiota transplantation in medically uncompromised obese individuals did not result in weight loss nor an increase of the gut hormone glucagon-like peptide 1 (GLP-1) at 12 weeks, but it did contribute to a decrease in primary bile acids as well as alterations in the stool microbiome.

“Currently, fecal microbiota transplantation [FMT] can only be performed clinically in the US to treat recurrent Clostridium difficile infection,” lead study author Jessica R. Allegretti, MD, MPH, said during a media briefing in advance of the annual Digestive Disease Week.

Dr. Jessica R. Allegretti, Brigham and Women's Hospital, Boston

Dr. Jessica R. Allegretti

“However, there is ongoing research to find out whether FMT works for other health conditions such as obesity, a condition which affects millions of people worldwide. [It’s] a condition that also increases the risk of developing many other illnesses, including diabetes, heart disease, and certain cancers. In my clinical practice, we regularly see patients who have not yet developed some of these other conditions related to obesity, but really do have difficulty losing weight. Through our research we wanted to focus on a population we call the medically uncompromised obese, and understand if FMT might be a viable treatment option for them,” she said.

Dr. Allegretti, director of the fecal microbiota transplant program at Brigham and Women’s Hospital, Boston, conducted a parallel study of 22 patients with a body mass index of 35 kg/m2 or higher who were metabolically healthy – defined as having no type 2 diabetes, nonalcoholic steatohepatitis (NASH), or metabolic syndrome. They randomized study participants 1:1 to receive 30 FMT capsules followed by two doses of 12 capsules over a 12-week period, or identical placebo capsules. A single healthy lean donor with a BMI of 17 kg/m2 was used.

The researchers assessed patients with a mixed meal tolerance test at baseline, week 6, and week 12 post-FMT, at which biomarkers GLP-1 and leptin were measured. Stool was collected at baseline and at one, four, six, eight, and 12 weeks post-FMT. The primary outcomes were safety and change in the area under the curve for GLP-1 at 12 weeks compared to baseline. Secondary endpoints include gut microbiome profiles and diversity as well as bile acid profiles at 12 weeks post FMT. Additional endpoints include a decrease in BMI and waist circumference at week 12. Standard stool microbiome and bile acid analysis was performed.

The mean age of the patients at baseline was 43 years, and their mean BMI was 41 kg/m2. Between baseline and week 12, the research observed no increase of GLP-1 in either group, while the change in leptin revealed an increase in the placebo group only (P less than .001). At week 12, no early changes in BMI were noted in either group (P = .51). No serious adverse events occurred in either arm.

Dr. Allegretti and her colleagues observed global signals of donor community engraftment following FMT, including an increase in alpha diversity and increased similarity to stool samples from the FMT donor – trends that were not observed in the placebo arm. In addition, bile acid analysis suggested a sustained decrease in taurocholic acid in the FMT arm, comparable with the donor – an effect that was not seen in the placebo arm. “We know that what leads to the germination of C. diff. spores is brought out by bile acids,” she said. “That’s one of the critical components of pathogenesis in that disease. My group has been able to show that after FMT, you regain bile acid homeostasis.”

Dr. Allegretti concluded her remarks by noting that the current study “adds an encouraging first step in trying to understand the role that the gut microbiome is playing in the pathogenesis of medically uncompromised obese patients. As a next step, we plan to seek more sensitive measures of GLP-1, as well as conduct additional research into varied doses of FMT capsules, as well as potentially investigating other microbial pathways to better understand the role the microbiome is playing in obesity.”

Somerville, Mass.–based Finch Therapeutics provided funding for the research. Dr. Allegretti reported having no financial disclosures.

SOURCE: Allegretti J et al. DDW 2019. Abstract 621.

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