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ARS Home » Midwest Area » Lexington, Kentucky » Forage-animal Production Research » Research » Publications at this Location » Publication #376808

Research Project: Sustainable Forage Production Systems for the Mid-South Transition Zone

Location: Forage-animal Production Research

Title: Fermentable fiber ameliorates experimental type I diabetes via IL-22 and short-chain fatty acids

Author
item ZOU, JUN - Georgia State University
item SJO, ZJEMDA - Georgia State University
item WANG, YANGLING - Georgia State University
item BRENT, ALEXIS - Georgia State University
item Flythe, Michael
item PELLIZZON, MICHAEL - Research Diets, Inc
item CHASSAING, BENOIT - Georgia State University
item GEWIRTZ, ANDREW - Georgia State University

Submitted to: Cell Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2021
Publication Date: N/A
Citation: N/A

Interpretive Summary: Type 1 diabetes (T1D), a major public health problem. The patient's genetics determine proneness to T1D, but evidence indicates that environmental factors, including diet and gut microbiota, play a role. Previous studies suggest that altering gut microbiota with diet may play a role in development of T1D. One way to alter gut microbiota is consumption of carbohydrates that are indigestible to humans and other animals, but digestible by bacteria One of these "soluble fibers" is the fructan, inulin, which is produced by chicory and some other plants. In these experiments, mice were treated with streptozotocin, which induces T1D. Feeding the mice inulin ameliorated the extent of the T1D, restoring glucose sensitivity. If the inulin was administered with a compound that inhibits inulin-ultilizing bacteria, then the benefits of inulin were decreased. It appeared that the inulin was fermented by the gut bacteria to produce short chain fatty acids or other metabolic products, which stimulated interleukin-22, an immune protein that is an important regulator of the intestinal barrier defense. Mice that could not make interleukin-22 were not protected from streptozotocin by inulin. These results support the idea that diets rich in fermentable fiber, or otherwise stimulate interleukin-22, might help manage type 1 diabetes.

Technical Abstract: Fermentable dietary fiber promotes insulin sensitivity thus mitigating type 2 diabetes. Here we report such protection extended to the streptozotocin (STZ)-induced model of type 1 diabetes. Specifically, low-fiber diets exacerbated STZ-induced diabetes while diets enriched with fermentable fiber strongly protected against, or treated, it. Fermentable fiber, inulin, but not insoluble fiber, cellulose, restored glycemic control and prevented loss of adipose depots, while reducing food and water consumption. Inulin normalized pancreatic function and markedly enhanced insulin sensitivity. Such amelioration of diabetes was associated with alterations in gut microbiota composition and was eliminated by antibiotic administration. Pharmacologic blockade of fermentation reduced inulin’s glycemic control benefits indicating a role for short-chain fatty acids in its beneficial action. Furthermore, inulin’s microbiota-dependent anti-diabetic impact correlated with restoration of IL-22, which was necessary and sufficient to ameliorate STZ-induced diabetes. Thus, fermentable fiber, SCFA, and/or IL-22 may have use in prevention and/or treatment of type 1 diabetes.