The Influence of Innate Immunity, Adaptive Immunity and Diet on Intestinal Microbiota Following Trichuris muris Infection

Trichuris trichiura infects nearly 500 million people worldwide, causing intestinal inflammation, malnutrition, and growth impairment, particularly in children from low‐resource settings. While host immunity is central to parasite clearance, diet and the gut microbiota may also modulate infection. Using the Trichuris muris model, we examined how immune competence and diet interact to influence worm burden, antibody responses, and gut microbiota composition. Wild‐type (WT), RAG1‐deficient (lacking adaptive immunity), and RAG1/ γ c‐deficient (lacking both adaptive and innate lymphoid immunity) mice were fed either a normal diet (ND) or high‐fat diet (HFD) and infected with a low dose of T. muris . WT mice on ND developed chronic infection with strong IgG2a/c responses, consistent with Th1‐biased immunity. In contrast, WT mice on HFD achieved near‐complete parasite clearance, accompanied by elevated IgG1 and reduced IgG2a/c titres, indicating diet‐induced Th2 bias. In RAG1‐ and RAG1/ γ c‐deficient mice, infection persisted under a normal diet but worm burdens were partially reduced on HFD, indicating that diet enhances parasite control through immune‐independent, possibly microbiota‐mediated pathways. Microbiota clustered by genotype and diet, with HFD‐associated enrichment of Bacteroides , Parabacteroides , and Blautia . These findings demonstrate that diet and immune status jointly shape helminth susceptibility through coordinated effects on host immunity and the gut microbiota.