High-sugar diet predisposes colitis via promoting mucus degrading bacteria in the gut

Abstract

Abstract The Western diet characterized by high fat and high sugar is considered a risk factor for many inflammatory disorders including colitis. However, the impact of dietary sugars, such as glucose, fructose, and sucrose, on colitis remains poorly understood. We, therefore, investigated the role of dietary simple sugars in colitis using dextran sulfate sodium (DSS) and Il10−/− mice models. We fed WT mice with high sugar in drinking water or diet, followed by administration of 2.5% DSS plus high-sugar diet. Sugar-fed wild-type mice showed extreme sensitivity to DSS-induced colitis. Consistently, Il10−/− mice spontaneously developed severe colitis with the consumption of high sugar. To understand the underlying mechanism of detrimental effect of dietary sugar on colitis, we measured pathophysiological changes in the healthy gut. Interestingly, while there was no induction of cell death, inflammatory mediators, and activation of inflammatory pathways, gut microbiota composition was significantly altered in sugar-fed healthy mice. Notably, the abundance of mucus degrading bacteria Akkermansia muciniphila and Bacteroides fragilis was increased. Consistently, bacteria-derived mucolytic enzymes were enriched and the colonic mucus layers were eroded in sugar-fed mice. Furthermore, germ-free mice colonized with microbiota from sugar-treated mice showed higher abundance of mucus degrading bacteria and increased colitis susceptibility. By demonstrating the complex interplay between high-sugar diet, gut microbiota composition, and intestinal mucus barrier, this study, therefore, elucidates a novel mechanism of colitis pathogenesis.