Increased gut microbial mucin foraging promotes clearance of a parasitic worm

Abstract

BACKGROUND & AIMSHost-secreted gastrointestinal mucus plays a key role in the expulsion of intestinal nematode parasites. A balance between mucin secretion by the host and the gut microbial mucin foraging is essential to maintain the intestinal homeostasis, yet little is known about how changes in the mucin-microbiome interactions affect worm infections. Here, we aimed to examine how mucin foraging activity by the microbiome changes the course of parasitic worm infections by modulating the host immune responses. METHODSWe utilized a gnotobiotic mouse model containing a synthetic human gut microbiota that allows for: 1) a complete removal of the mucin-degrading bacteria from the community; and 2) diet-driven manipulation of the microbiota toward mucin foraging. We infected mice with a murine nematode, Trichuris muris, which resembles human infection with Trichuris trichiura. We examined the temporal dynamics of worm infection including worm burden and the host immune responses, and coupled these readouts to the microbial changes and mucin foraging activity. RESULTSThe absence of mucin-degrading bacteria in the microbiota enhances susceptibility to parasitic infection--evidenced by higher worm number--by promoting stronger Th1 immune responses. Dietary fiber deprivation increases the microbial mucin-foraging activity, which coincides with a shift in host immune responses from susceptible (chronic, Th1 type) to resistant (acute, Th2 type), thereby promoting worm clearance. CONCLUSIONSOur results provide mechanistic insights into how the colonic mucin-degrading bacteria promote anti-parasitic immunity through modulation of the host immune responses. Our study documents a clinically-relevant, novel link in the microbiome-parasite-host immune axis that is useful prerequisite knowledge in managing parasitic infections.