Fecal Microbiota Transplant Could Aid Weight Loss

Jessica Allegretti, MD, MPH

Gut microbes from a lean donor could help obese, but metabolically healthy recipients lose weight, according to study presented at Digestive Disease Week (DDW) 2019 in San Diego, CA.

The study, which was presented by Jessica Allegretti, MD, MPH, Director, Fecal Microbiota Transplant Program, Brigham and Women's Hospital, Boston, MA, explored whether an alteration in the gut microbiome as a result of fecal microbiota transplantation (FMT) might benefit metabolically healthy obese patients.

"In our clinic, we see patients who really don't have any other medical problems, but just cannot lose weight,” Allegretti explained. “It is a very important patient population that we really wanted to give focus to and try to help understand."

Allegretti and colleagues randomized 22 patients on 1:1 ratio to receive either 30 FMT capsules followed by 2 doses of 12 capsules over a 12-week period or placebo. All participants had BMI of 35kg/m² or higher at study entry, but were without diabetes type 2, nonalcoholic steatohepatitis or metabolic syndrome.

The dosing pattern of the FMT was derived from the investigators' experience in treating clostridium difficile and chronic diseases like inflammatory bowel disease, wherein successful retention of the microbiota after transplantation (engraftment) would likely persist in the former, but tend to be transient in the latter.

The FMT was obtained from a single lean, female donor (BMI=17) through the stool bank, OpenBiome, which, Allegretti pointed out, collects a variety of data on each donor, including on diet and food frequency.

"When you compare this donor to the average female stool donor, she actually ate significantly more calories, and, the thought was that she was lean but metabolically active," Allegretti said.

The investigators administered a mixed meal tolerance test to each participant at baseline and at weeks 6 and 12, with measures of glucagon-like peptide 1 (GLP-1) and leptin. Stool was collected and the microbiome profiled at baseline and weeks 1,4,6,8, and 12. Additional measurements of bile acid profile, as well as changes in weight, BMI and waist circumference at were taken week 12.

"We went in with a hypothesis that we would see changes in GLP-1, which is a gut hormone that we know is mediated by the gut microbiome, and we know is important for the satiety reflex, slowing gastric emptying and, therefore, augmenting weight loss," Allegretti explained.

Participants were instructed not to change their dietary patterns, and to provide dietary histories at each visit to increase likelihood that outcomes would reflect the FMT rather than other modifications.

Investigators reported success in achieving engraftment in the FMT recipients, with increase in alpha diversity and increased similarity to stool samples from the FMT donor, which were not observed in the placebo group. Of the 200 operational taxonomic units identified as engrafting from the donor, Allegretti and colleagues note that many had previously been found to be enriched in a separate normal BMI healthy cohort (n=60).

There was also a change in bile acids profile in the FMT arm but not with placebo, with a sustained decrease in taurocholic acid that was comparable with the donor. There was not, however, an increase of GLP-1 at week 12 compared to baseline, nor was there a change in BMI.

The report, Fecal Microbiota Transplantation for the Treatment of Obesity: A Randomized, Placebo-Controlled Pilot Trial, was presented at the Digestive Disease Week conference, May 9, 2019 in San Diego, CA.