Fermentable Fiber Ameliorates Experimental Type I Diabetes Via IL-22 and Short-Chain Fatty Acids

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.