A dietary fiber limits autoimmune neuroinflammation by restricting Th1 activation, polarization, and migration

Abstract

Abstract Dietary fibers and their breakdown products have been shown to limit inflammation in multiple disease contexts. However, the term “dietary fiber” encompasses a biochemically diverse family of carbohydrates, and it remains unknown how different fiber sources influence immune cell function. To address this question, we assessed the immunomodulatory capacity of different fiber types in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). C57BL/6 mice were fed a control diet (5% cellulose) or diets enriched (30%) with resistant starch, inulin, pectin, or guar gum for 2 weeks prior to EAE induction. A diet rich in guar gum uniquely ameliorated the clinical, pathological, and immunological features of EAE. Limited central nervous system (CNS) infiltration of IFNγ+CD4+ T cells (Th1s) in guar gum-fed mice could be attributed to T cell-intrinsic impairment Th1 activation and polarization. Nanostring nCounter transcriptional analyses revealed downregulation of migration-associated markers in CD4+ T cells isolated from guar gum/EAE mice, which was supported by reduced cell-surface expression of integrins involved in migration into the CNS. Functionally, this translated to limited migration of guar gum-derived encephalitogenic Th1s into the CNS upon adoptive transfer into control-fed recipients, which reduced incidence and severity of EAE. However, the 16S rRNA microbiome signature and short chain fatty acid profiles were not unique in comparison to other fiber-supplemented diets, indicating a novel mechanism of action from those previously ascribed in high fiber diet studies. These data confirm the individuality of dietary fibers and identify a novel immunomodulatory function of guar gum. This project was supported by the endMS doctoral studentship program (Multiple Sclerosis Society of Canada) (NMF, JRA), the Canadian Institutes for Health Research (PJT-148909), and the Canada Research Chair program (LCO).