Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health

Abstract

Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function.

Mannan Oligosaccharide Suppresses Lipid Accumulation and Appetite in Western‐Diet‐Induced Obese Mice Via Reshaping Gut Microbiome and Enhancing Short‐Chain Fatty Acids Production

“…Indigestible carbohydrates including inulin, galacto‐oligosaccharide, xylooligosaccharide, and soybean oligosaccharides, have been found to suppress obesity by the alteration of the gut microbiome and microbial metabolites . Similarly, we also found that MOS increased the SCFAs production and balanced the microbiome in WD‐fed mice.…”

Influence of Early Life, Diet, and the Environment on the Microbiome

“…81 In mouse models of obesity, fiber supplementation prevented inflammation and metabolic syndrome by restoring IL-22 production within the colon. 82 Diets high in fiber tend to have higher microbial richness and diversity with an abundance in such genera as Prevotella and Treponema. 83 These shifts have been linked to a decreases in inflammatory signaling, protection against obesity, and possibly decreases in the presence of colorectal cancer.…”

Obesity and severe asthma

“…Regarding prebiotics, in mice, dietary supplementation with inulin, a fermentable fiber that results in SCFA generation, but not cellulose, an insoluble fiber that is not readily fermented, provides protection from the metabolic effects of high fat diets, including glucose tolerance and insulin resistance (132). There is some evidence that inulin might also be beneficial in asthmatics.…”