|ZOU, JUN - Georgia State University|
|CHASSAING, BENOIT - Georgia State University|
|SINGH, VISHAL - Pennsylvania State University|
|PELLIZZON, MICHAEL - Pennsylvania State University|
|ULMAN, EDWARD - Pennsylvania State University|
|RICCI, MATTHEW - Pennsylvania State University|
|VIJAY-KUMAR, MATAM - Pennsylvania State University|
|GEWIRTZ, ANDREW - Georgia State University|
Submitted to: Cell Host and Microbe
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/23/2017
Publication Date: 1/10/2018
Citation: Zou, J., Chassaing, B., Singh, V., Pellizzon, M., Ulman, E., Ricci, M., Flythe, M.D., Vijay-Kumar, M., Gewirtz, A.T. 2018. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host and Microbe. 23:41-53.
Interpretive Summary: Bacteria in the colon ferment “dietary fiber” to produce short-chain fatty acids (SCFA). It is thought that SCFA have protective effects against metabolic disease that is associated with a high-fat diet. This study found that a high-fat diet dramatically changed the bacteria in the gut, and resulted in decreased levels of an important signal molecule called interleukin-22. An easily fermentable fiber, called inulin, restored normal levels of bacteria and interleukin-22. Inulin-induced interleukin-22 prevented gut atrophy and metabolic disease. These results indicate that the dietary fiber, inulin, protected against metabolic disease by promoting normal bacteria and restoring interleukin-22 mediated gut function.
Technical Abstract: Dietary supplementation with fermentable fiber is thought to suppress metabolic syndrome via production of short-chain fatty acids (SCFA), which activate the free fatty acid receptors including GPR43. However, herein, we demonstrate that fermentable (inulin), but not insoluble (cellulose) fiber, markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, which was not impaired by either blockade of SCFA production nor genetic ablation of GPR43. Rather, we found that HFD decimates gut microbiota resulting in loss of IL-22 expression and enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI) and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, IL-22 expression, enterocyte proliferation, and anti-microbial gene expression in a microbiota dependent manner, as assessed by antibiotic and germfree approaches. Moreover, inulin-induced IL-22 expression prevented microbiota encroachment/translocation and protected against LGI and metabolic syndrome. Thus, we conclude that fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function.