Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Cell Host Microbe. 2018 Jan 10;23(1):41-53.e4. doi: 10.1016/j.chom.2017.11.003. Epub 2017 Dec 21.
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.
膳食纤维补充剂可抑制肥胖和相关代谢综合征参数。微生物群产生的纤维衍生的短链脂肪酸（SCFA）和游离脂肪酸受体，包括 GPR43，被认为介导这些作用。我们发现，可发酵（菊粉）纤维，但不可发酵（纤维素）纤维，可显著保护小鼠免受高脂肪饮食（HFD）诱导的代谢综合征，而抑制 SCFA 产生或 GPR43 基因缺失均不会显著削弱这种作用。相反，HFD 会大量破坏肠道微生物群，导致肠细胞增殖减少，导致微生物群侵占、低度炎症（LGI）和代谢综合征。通过抗生素和无菌方法评估，用菊粉丰富 HFD 可恢复微生物群负荷、白细胞介素-22（IL-22）产生、肠细胞增殖和抗菌基因表达，这是一种依赖于微生物群的方式。菊粉诱导的 IL-22 表达需要先天淋巴细胞，可防止微生物群侵占，并可预防 LGI 和代谢综合征。因此，可发酵纤维通过滋养微生物群来恢复 IL-22 介导的肠细胞功能，从而预防代谢综合征。
