Gut microbiota response to Enterocytozoon bieneusi infection in wild rodents: enhanced vitamin B and K2 biosynthesis pathways.

Enterocytozoon bieneusi (E. bieneusi) is a pathogenic microsporidian that affects immunocompromised individuals, including those with HIV, and represents a major cause of diarrhea. It can severely impact human health, causing gastrointestinal disease, nutritional deficits, and life-threatening complications. However, the microbial mechanisms by which E. bieneusi affects host nutrition are not well understood. Wild rodents have long been considered valuable models for studying human diseases due to similarities in gut microbiota dynamics and immune responses, making them particularly relevant for investigating parasitic infections. Here, we assembled a comprehensive catalog of 9,929 non-redundant microbial genomes from wild rodent gut metagenomes and evaluated their potential for B vitamins and vitamin K2 biosynthesis using comparative functional genomics. We identified 2,307 genomes encoding complete pathways for de novo biosynthesis of at least one essential vitamin, though no single genome encoded all pathways, indicating a distributed metabolic capacity within the microbial community. Infection with E. bieneusi significantly altered the microbial composition and the potential for vitamin biosynthesis, with a notable expansion of Methanobacteriota and reprogramming of pyridoxine (vitamin B6) biosynthesis pathways. These changes reveal a functional shift in microbial metabolism in response to parasitic pressure. By elucidating the microbial basis of vitamin biosynthesis in wild rodents and the impact of E. bieneusi infection on microbial functions, this study provides new insights into the role of gut microbiota in maintaining host health and supporting nutrient provision under parasitic stress. Moreover, the findings will provide valuable insights into the prevention and control of E. bieneusi infection in a variety of host, including humans.