Dietary Emulsifiers Directly Impact Adherent-Invasive E. coli Gene Expression to Drive Chronic Intestinal Inflammation

Summary Dietary emulsifiers carboxymethylcellulose (CMC) and polysorbate-80 (P80) disturb gut microbiota, promoting chronic inflammation. Mice with minimal microbiota are protected against emulsifiers’ effects, leading us to hypothesize that these compounds might provoke select pathobionts to promote inflammation. Gnotobiotic wild-type (WT) and interleukin-10 (IL-10)−/− mice were colonized with Crohn’s-disease-associated adherent-invasive E. coli (AIEC) and subsequently administered CMC or P80. AIEC colonization of GF and altered Schaedler flora (ASF) mice results in chronic intestinal inflammation and metabolism dysregulations when consuming the emulsifier. In IL-10−/− mice, AIEC mono-colonization results in severe intestinal inflammation in response to emulsifiers. Exposure of AIEC to emulsifiers in vitro increases its motility and ability to adhere to intestinal epithelial cells. Transcriptomic analysis reveals that emulsifiers directly induce expression of clusters of genes that mediate AIEC virulence and promotion of inflammation. To conclude, emulsifiers promote virulence and encroachment of pathobionts, providing a means by which these compounds may drive inflammation in hosts carrying such bacteria.
Graphical Abstract
Highlights • Dietary emulsifiers alter the intestinal microbiota, promoting chronic inflammation • Select pathobionts are required to mediate the detrimental effects of emulsifiers • Emulsifiers directly induce the expression of bacterial virulence genes • Microbiota-based dietary intervention appears warranted
Through gnotobiotic and molecular approaches, Viennois et al. demonstrate that in mice, the ability of a dietary emulsifier to promote chronic intestinal inflammation and colitis-associated cancer is mediated by the ability of these compounds to directly induce the expression of clusters of genes that mediate virulence of a select pathobiont.