Inhibition of Th1 activation and differentiation by dietary guar gum ameliorates experimental autoimmune encephalomyelitis

Abstract

Dietary fibers are potent modulators of immune responses that can restrain inflammation in multiple disease contexts. However, dietary fibers encompass a biochemically diverse family of carbohydrates, and it remains unknown how individual fiber sources influence immunity. In a direct comparison of four different high-fiber diets, we demonstrate a potent ability of guar gum to delay disease and neuroinflammation in experimental autoimmune encephalomyelitis, a T cell-mediated mouse model of multiple sclerosis. Guar gum-specific alterations to the microbiota are limited, and disease protection appears to be independent of fiber-induced increases in short-chain fatty acid levels or regulatory CD4⁺ T cells. Instead, CD4⁺ T cells of guar gum-supplemented mice are less encephalitogenic due to reduced activation, proliferation, Th1 differentiation, and altered migratory potential. These findings reveal specificity in the host response to fiber sources and define a pathway of fiber-induced immunomodulation that protects against pathologic neuroinflammation.

Keywords: CD4+ T cells; CP: Immunology; EAE; MS; dietary fiber; experimental autoimmune encephalomyelitis; microbiota; multiple sclerosis.