Diets high in saturated fat increase risk for IBD in genetically susceptible hosts via induction of immunogenic microflora

Inflammatory Bowel Diseases (IBD) affect over 1.4 million Americans with 30,000 newly diagnosed cases per year and no known cure. Diets high in saturated fat (SF) have been linked with increased risk for IBD, although potential mechanisms underlying this association have not been identified. Pilot data in conventional mice showed a high SF diet promotes the growth of Bilophila wadsworthia ( B.wad ), a non‐abundant proteobacteria that produces genotoxic hydrogen sulfide, which led to development of colitis. This study elucidates the mechanism by which high SF diets confer B.wad's immunogenicity. Germ‐free (GF) IL10 −/− mice were adapted to either a low fat (LF) or SF diet and gavaged with a pure strain of B.wad . After 5 wk B.wad survived only in mice consuming the SF diet, with none surviving in LF mice. ELISA and FACS analyses of proinflammatory cytokines in colonic mucosa and mesenteric lymph nodes displayed elevated IL12p40, IL12p70, and IFNγ, and low level IL6, TNFα, and IL17 in only the SF+ B.wad mice. This suggests B.wad strongly polarizes T‐cells toward a local Th1 immune response‐ a hallmark of overt colitis. The control group, GF IL10 −/− mice consuming the LF or SF diet without B.wad gavage, showed no such immune response. This is the first study to demonstrate SF‐induced B.wad growth provides a significant risk factor for developing IBD in a genetically susceptible host. Grant Funding Source : National Institutes of Health T32 and F31