Wheat fiber-induced peripheral regulatory T-cells suppress development of colitis

Abstract Reduced dietary fiber intake is associated with, and may have contributed to, the post-mid-20 th century increase in immune-mediated chronic inflammatory diseases, including inflammatory bowel disease. Reduced fiber intake has resulted, in part, from highly refined foods. For example, modern methods of producing bread removes much of the fiber naturally present in wheat kernels. Accordingly, we hypothesized that wheat fiber might protect against chronic inflammatory diseases. We tested this notion in a murine T-cell transfer colitis model. Rag1 -/- mice were fed open-source low-fiber diets enriched, or not with wheat fiber (WF) and then administered CD45Rb hi T-cells. WF conferred robust protection in this colitis model as assessed by an array of clinical, histopathologic, morphologic, and immune-related parameters. WF’s protection against colitis associated with a microbiota-dependent increase in Foxp3 + T-cell (Tregs), which could be recapitulated in vitro. WF did not induce Tregs in CNS1 -/- mice nor did WF protect against T cell transfer colitis driven by transplant of colitogenic T-cells from CNS1 -/- mice. Thus, enriching diet with WF has potential to promote microbiota-dependent peripheral Treg development and, consequently, protect against chronic inflammatory diseases.