Inulin fermentable fiber ameliorates type I diabetes via IL22 and short-chain fatty acids in experimental models

Authors: ZOU, JUN - Georgia State University; REDDIVARI, LAVANYA - Purdue University; SHI, ZHENDA - Georgia State University; LI, SHIYU - Purdue University; WANG, YANGLING - Georgia State University; BRETIN, ALEXIS - Georgia State University; NGO, VU - Georgia State University; Flythe, Michael; PELLIZZON, MICHAEL - Research Diets, Inc; CHASSAING, BENOIT - Georgia State University; GEWIRTZ, ANDREW - Georgia State University

Submitted to: Cellular and Molecular Gastoenterology and Hepatology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2021
Publication Date: 4/30/2021
Citation: Zou, J., Reddivari, L., Shi, Z., Li, S., Wang, Y., Bretin, A., Ngo, V.L., Flythe, M.D., Pellizzon, M., Chassaing, B., Gewirtz, A. 2021. Inulin fermentable fiber ameliorates type I diabetes via IL22 and short-chain fatty acids in experimental models. Cellular and Molecular Gastoenterology and Hepatology. 12(3):983-1000. https://doi.org/10.1016/j.jcmgh.2021.04.014.
DOI: https://doi.org/10.1016/j.jcmgh.2021.04.014

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.