Recipient’s gut bacteria make-up may drive faecal transplant response

The gut microbiota composition of the recipient may determine the effectiveness of a faecal transplant in reducing insulin resistance, according to a new study in Cell Metabolism.

Temporary improvements in insulin resistance were seen in half of the subjects with metabolic syndrome who were given faecal material transplants (FMT), reports a study led by the University of Amsterdam.

In the small Dutch study, faecal material given by lean donors to individuals who exhibited insulin resistance, a precursor to type-2 diabetes. The scientists found that analysis of the recipient’s gut bacteria make-up predicted the success of the treatment.

"We have now shown that you can categorize people based on their faecal samples," commented senior author Max Nieuwdorp. "This allows us to classify diseases with more sensitivity."

“The fifty-fifty responder-to-non-responder rate surprised me," added Nieuwdorp. "I thought we would have fewer people respond to the transplant."

The scientists found that the responders were characterised by lower initial diversity of faecal bacteria prior to the transplant. This confirmed earlier findings that suggested lower diversity within the microobiome predicted success of treatment.    

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

Study details

Thirty-eight obese males with metabolic syndrome were recruited into the randomised controlled trial. Additionally, 11 lean donors with ‘healthy’ gut bacteria acted as donors of faecal material. The researchers established baseline measurements of insulin resistance and microbiome composition using blood and faecal samples.

Each obese man was paired with a lean donor and given a FMT. Six weeks after the FMT, the researchers obtained further blood and stool samples.

They found that 50% of the trial subjects had lower insulin resistance, together with changes in their gut bacteria constituents.

However, neither single nor multiple FMTs had a significant effect on either hepatic or peripheral measures of insulin sensitivity 18 weeks after the initial transplant. Additionally, the microbiome composition of the recipients had returned to that at baseline.

The scientists noted that the lack of long-term effect was consistent with previous research, which had suggested the existence of a ‘personal core faecal microbiome’. They also implied that without changes to factors such as diet and lifestyle, reversion to the core microbiome make-up was understandable.

“It is likely that the host immune system develops resilience, which, in combination with the adherence of one’s own lifestyle, including diet, could explain the return of intestinal microbiota composition to the baseline situation,” wrote the researchers.

Nevertheless, the scientists believe that the study findings highlight the potential for developing future treatment strategies.

“We 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," concluded Nieuwdorp.

Source:  Cell Metabolism

Volume 26, Issue 4, p611–619.e6    DOI: 10.1016/j.cmet.2017.09.008

“Improvement of Insulin Sensitivity after Lean Donor Faeces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition”

Authors:  Ruud S. Kootte, Max Nieuwdorp  et al