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

Reduced dietary fiber intake is associated with, and may have contributed to, the post-mid-20th century increase in immune-mediated chronic inflammatory diseases, including inflammatory bowel disease (IBD). Reduced fiber intake has resulted, in part, from increased consumption of highly refined foods including those made from white flours, generation of which involves removal of much of the fiber naturally present in wheat kernels. Accordingly, we hypothesized that wheat fiber (WF) might protect against chronic inflammatory diseases. We tested this notion in a murine T-cell-transfer colitis model. Rag1^-/- mice were fed purified (open-source) low-fiber diets enriched, or not, with 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-cells (Tregs), which could be recapitulated in vitro. WF did not induce Tregs in mice lacking conserved non-coding sequence 1 knock-out (CNS1), which is known to drive peripheral Treg development, 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.