Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways

Cell Rep. 2016 Jun 21;15(12):2809-24. doi: 10.1016/j.celrep.2016.05.047.


The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103(+) dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103(+) DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103(+) DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Bacteria / metabolism*
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Dietary Fiber / pharmacology*
  • Fatty Acids, Volatile / metabolism*
  • Feeding Behavior
  • Food Hypersensitivity / immunology*
  • Food Hypersensitivity / prevention & control*
  • Gastrointestinal Microbiome / drug effects
  • Immune Tolerance / drug effects*
  • Immunoglobulin A / immunology
  • Integrin alpha Chains / metabolism
  • Mice, Inbred C57BL
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Nicotinic / metabolism
  • Signal Transduction / drug effects*
  • Vitamin A / metabolism


  • Antigens, CD
  • Dietary Fiber
  • Fatty Acids, Volatile
  • Ffar2 protein, mouse
  • Hcar2 protein, mouse
  • Immunoglobulin A
  • Integrin alpha Chains
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • alpha E integrins
  • Vitamin A