Fecal transplant improves metabolic syndrome in patients with greater initial microbial diversity

Fecal microbiota transplantation from lean donors provided short-term improvements in peripheral insulin sensitivity in about half of obese men with metabolic syndrome enrolled in a small clinical trial in the Netherlands.

Investigators found that the composition of the patients’ fecal microbiota at baseline predicted their response to FMT, a finding they said could help lead to personalized FMT for metabolic syndrome.

“We have now shown that you can categorize people based on their fecal samples,” Max Nieuwdorp, MD, PhD, of the department of internal and vascular medicine at the University of Amsterdam, said in a press release. “This allows us to classify diseases with more sensitivity.”

Building on a previous pilot study of FMT for metabolic syndrome, Nieuwdorp and colleagues performed a double-blind trial in which they randomly assigned 38 men with obesity who met criteria for metabolic syndrome to receive autologous FMT (controls) or FMT from one of 11 lean donors. They also randomly assigned a subgroup of patients to receive an additional FMT 6 weeks later at first follow-up, and evaluated all patients at 18 weeks for long-term effects.

Blood samples showed that half of those who received FMT from a lean donor experienced significantly improved insulin sensitivity after 6 weeks, from 25.8 µmol kg^–1 min^–1 (19.3-34.7) to 28.8 (21.4-36.9) µmol kg^–1 min^–1 (P < .05).

“The fifty-fifty responder-to-non-responder rate surprised me,” Nieuwdorp said in the press release. “I thought we would have fewer people respond to the transplant.”

Additionally, fecal samples showed accompanying changes in gut microbiota composition among responders.

“Several fecal bacterial species that were different between autologous and allogenic FMT have been linked to human metabolism,” including Lactobacillus salivarius, Butyrivibrio, Clostridium symbiosum and Eubacterium, Nieuwdorp and colleagues wrote.

However, these metabolic and microbial changes did not persist at 18 weeks, leading researchers to conclude that the benefits of lean donor FMT were transient. No serious adverse events occurred throughout the study, they noted.

After further evaluating the participants’ stool samples, Nieuwdorp and colleagues also found that non-responders showed lower microbial diversity at baseline, and that they could predict response based primarily on the abundance of four species (receiver operating characteristic AUC = 0.88).

They also found that responders showed changes in fasting plasma metabolites.

“Although the overall metabolic effects of lean donor FMT are modest and show a wide variety between patients, our data do suggest that changes in plasma metabolites (predominantly amino acids), as a consequence of the altered intestinal microbiota composition, might be one explanation for the beneficial effects of lean donor FMT on peripheral insulin sensitivity,” investigators wrote.

Nieuwdorp concluded that he and his team “have shown some major effects and started to see that there could be some real power to treat people by replenishing missing intestinal bacterial strains.” – by Adam Leitenberger

Disclosures: Nieuwdorp reports he is a co-founder and scientific advisor for Caelus Pharmaceuticals. Please see the full review for a list of all other authors’ relevant financial disclosures.