BACKGROUND amp; AIMS Host-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 mucintextendashmicrobiome interactions affect worm infection. Here, we aimed to examine how increased mucin foraging activity by the microbiome changes the course of the parasitic infection by modulating the host immune responses.METHODS We employed a gnotobiotic mouse model containing a 14-member synthetic human gut microbiota that facilitates functional interpretations, including diet-driven manipulation of the microbiota toward mucin foraging. We infected the mice with a robust murine nematode, Trichuris muris, that closely resembles human infection with Trichuris trichiura. We investigated the temporal dynamics of worm infection including worm burden and the host immune responses, and connected these readouts to the microbial changes and metabolic activity toward mucin foraging.RESULTS The microbial mucin foraging was further increased during worm infection only in mice with pre-enhanced mucin degrading capacity. The elevated mucin foraging coincides with a shift in host immune responses from susceptible (chronic, Th1 type) to resistant (acute, Th2 type), which promotes worm clearance. The relative abundances of mucin-generalist bacteria drammatically increased during worm clearance, but not during worm retention.CONCLUSIONS These results point to a mechanism whereby skewing the metabolic activity of the microbiome toward mucin glycoproteins promotes resistance to worm infection. Our study documents a clinically-relevant, novel link in the microbiometextendashparasitetextendashhost immune axis, which is important prerequisite knowledge in treating parasitic infections.Competing Interest StatementMahesh S. Desai works as a consultant and an advisory board member at Theralution GmbH, Germany.
|Cold Spring Harbor Laboratory Press