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Abstract
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.