Could Fecal Transplant Improve Insulin Sensitivity?

By Will Boggs MD

October 04, 2017

NEW YORK (Reuters Health) - Fecal microbiota transplant (FMT) from a lean donor transiently improves insulin sensitivity in some obese patients with metabolic syndrome, researchers report.

"Based on our study results, we feel that gut microbiota play a minor (but significant) role in human glucose metabolism,” Dr. Max Nieuwdorp from the University of Amsterdam, in the Netherlands, told Reuters Health by email. “Moreover, we were able to show that we can predict based on a baseline fecal sample who will respond to lean-donor FMT and who will not. This will help to design future targeted intervention studies.”

Dr. Nieuwdorp and colleagues showed in an earlier pilot study that lean-donor FMT into obese males with metabolic syndrome was associated with improved glucose metabolism and alterations in intestinal microbiota composition.

This time, they investigated the short- and long-term effect of lean-donor FMT on gut microbiota composition and its relationship with insulin resistance in a larger group of 38 obese men with metabolic syndrome. The findings were published online October 3 in Cell Metabolism.

From baseline to 6 weeks after lean-donor FMT, peripheral insulin sensitivity had improved from 25.8 to 28.8 micromoles/kg/min. Autologous FMT, however, had no effect on insulin sensitivity.

Hemoglobin A1c also decreased slightly in the lean-donor FMT group, but other metabolic parameters were not affected.

By 18 weeks, neither single nor repeated lean-donor FMT had significantly affected hepatic or peripheral insulin sensitivity.

Lean-donor FMT was associated with significant increases in fecal acetate levels, which are inversely related to insulin resistance in humans.

Metabolic responders to lean-donor FMT had lower initial fecal microbiota diversity, along with higher abundance of Subdoligranulum variabile and Dorea longicatena - and lower abundance of Eubacterium ventriosum and Ruminococcus torques in baseline fecal samples, compared with nonresponders.

“Based on these findings, we conclude that for future interventions, determining baseline fecal microbiota composition might aid in predicting efficacy of treatment,” the researchers write.

“In the next few years, we hopefully will be able, based on the fecal gut microbiota composition, to disentangle who will benefit from gut microbiota-based intervention and who will not,” Dr. Nieuwdorp said by email.

Dr. Amir Zarrinpar from the University of California, San Diego, in La Jolla, who recently reviewed the use of FMT for treating obesity and metabolic syndrome, told Reuters Health by email, "Based on previous studies in mice, and interesting case studies in humans, the prevailing thought was that FMT could potentially cause major metabolic changes in the recipient. However, it is disappointing that the changes in insulin sensitivity were not detectable on clinically meaningful measures, such as weight, HbA1c, or baseline glucose.”

“The most important implication is that human insulin sensitivity can be affected through the gut microbiome,” he said. “Although scientists studied the metabolic effects of human microbiome by using gnotobiotic mice, this study more definitively shows that the microbiome does play a role in human metabolism and that human metabolism can be changed through the gut microbiome.”

“As the authors stated, FMT was the only intervention done in these patients,” Dr. Zarrinpar said. “It's not clear whether FMT would have amplified the effects of behavioral interventions such as caloric restriction or the adoption of a healthier diet. It is possible that lifestyle modification in addition to FMT could sustain the microbiome acquired from lean donors for longer and actually lead to clinically significant changes in diabetes measures.”

“My biggest worry is that patients may misinterpret these results and think that the paper shows that an FMT can help with their diabetes,” he added. “In fact, that paper shows that performing FMT on patients with diabetes had limited and transient benefits, and, hence, not worth the risks.”


Cell Metab 2017.