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

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.

Keywords: germ-free mice; intestinal inflammation; metabolic syndrome; microbiota encroachment; short-chain fatty acids.

MeSH terms

  • Adiposity / drug effects
  • Animals
  • Bifidobacterium / growth & development
  • Cell Proliferation / drug effects
  • Diet, High-Fat / adverse effects*
  • Dietary Fiber / therapeutic use*
  • Dietary Supplements
  • Epithelial Cells / metabolism
  • Fatty Acids, Volatile / metabolism*
  • Gastrointestinal Microbiome / drug effects
  • Homeodomain Proteins / genetics
  • Interleukin-22
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / growth & development
  • Intestinal Mucosa / microbiology*
  • Inulin / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / prevention & control
  • Receptors, G-Protein-Coupled / genetics*


  • Dietary Fiber
  • Fatty Acids, Volatile
  • Ffar2 protein, mouse
  • Homeodomain Proteins
  • Interleukins
  • Receptors, G-Protein-Coupled
  • RAG-1 protein
  • Inulin