Gut microbiota response to Enterocytozoon bieneusi infection: enhanced vitamin B and K 2 pathways

Enterocytozoon bieneusi ( E. bieneusi ) is a highly pathogenic parasite that infects immunocompromised individuals, especially HIV patients, and is a leading cause of diarrhea in these populations. It significantly impacts human health, causing severe gastrointestinal symptoms, malnutrition, and potentially life-threatening complications. However, the microbial mechanisms behind E. bieneusi infection and its effects on host nutrition are not well understood. Wild rodents have long been considered a valuable model for studying human diseases due to their similar gut microbiota dynamics and immune responses to humans, making them particularly relevant for investigating parasitic infections. Here, we assembled a comprehensive catalog of 9,929 non-redundant micr obial genomes from wild rodent gut metagenomes and evaluated their potential for B vitamin and vitamin K ₂ 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 B ₆ ) 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 offers new insights into the role of gut microbiota in maintaining host health and nutrient provisioning under parasitic stress. Moreover, the findings will also provide valuable insights into prevention and control of E. bieneusi infection in a variety of host, including humans.