Abstract
Dietary emulsifiers, including carboxymethylcellulose (CMC) and polysorbate 80 (P80), perturb gut microbiota composition and gene expression, resulting in a microbiota with enhanced capacity to activate host pro-inflammatory gene expression and invade the intestine's inner mucus layer. Such microbiota alterations promote intestinal inflammation, which can have a variety of phenotypic consequences including increased adiposity. Bacterial flagellin is a key mediator of emulsifiers' impact in that this molecule enables motility and is itself a pro-inflammatory agonist. Hence, we reasoned that training the adaptive mucosal immune system to exclude microbes that express flagellin might protect against emulsifiers. Investigating this notion found that immunizing mice with flagellin elicited an increase in mucosal anti-flagellin IgA and IgA-coated microbiota that would have otherwise developed in response to CMC and P80 consumption. Yet, eliciting these responses in advance via flagellin immunization prevented CMC/P80-induced increases in microbiota expression of pro-inflammatory agonists including LPS and flagellin. Furthermore, such immunization prevented CMC/P80-induced microbiota encroachment and deleterious pro-inflammatory consequences associated therewith, including colon shortening and increased adiposity. Hence, eliciting mucosal immune responses to pathobiont surface components, including flagellin, may be a means of combatting the array of inflammatory diseases that are promoted by emulsifiers and perhaps other modern microbiota stressors.