Gut-microbial metabolites protect against type 1 diabetes in mice

Reuters Health Information: Gut-microbial metabolites protect against type 1 diabetes in mice

Gut-microbial metabolites protect against type 1 diabetes in mice

Last Updated: 2017-04-03

By Will Boggs MD

NEW YORK (Reuters Health) - The gut-microbial metabolites acetate and butyrate protect against type 1 diabetes in the nonobese diabetic (NOD) mouse, researchers report.

In a paper online March 27 in Nature Immunology, they note that acetate promotes gut barrier function, butyrate has anti-inflammatory effects and short-chain fatty acids influence gene transcription in regulatory T cells.

Dr. Eliana Marino from Monash University in Clayton, Australia, and colleagues used diets that yielded large amounts of acetate or butyrate to determine the individual effects, as well as the combined effects of short-chain fatty acids, on the development of diabetes in NOD mice.

In untreated mice, peripheral blood concentrations of both acetate and butyrate (but not propionate) were inversely related to progression to diabetes, the team found.

Diets resulting in increased release of acetate or butyrate significantly reduced the incidence of diabetes, and mice fed these diets had a larger number of pancreatic islets with no infiltration versus mice fed a normal diet.

A combination diet provided complete protection from diabetes.

Acetate decreased the frequency of autoreactive T cells and the concentrations of IL-21, an inflammatory cytokine required for development of diabetes in NOD mice, whereas butyrate promoted the frequency and function of regulatory T cells. Both short-chain fatty acids were associated with increased concentrations of IL-22, a cytokine that maintains the integrity of the gut mucosal barrier.

“Regardless of the underlying cause of T1D in humans, the application of a large amount of acetate and/or butyrate could be an effective intervention,” the researchers conclude. “A medicinal food approach might be particularly relevant for T1D, as this disease usually arises in children and young adults, for whom drug-safety considerations are paramount and detection of autoantibodies allows intervention before the onset of clinical diabetes.”

Dr. Jayne Danska from the Hospital for Sick Children Research Institute at the University of Toronto, Canada, told Reuters Health by email, "These data are solely from inbred mice and cannot be generalized to diverse humans, especially young children."

"None of these data should be used to change diet for patients at risk of type 1 diabetes," Dr. Danska, who was not involved in the study, cautioned.

The authors reported no conflicts of interest.

Dr. Marino did not respond to a request for comments.


Nature Immunol 2017.

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