A bacterial sialidase mediates early life colonization by a pioneering gut commensal

Abstract

ABSTRACTThe early microbial colonization of the gastrointestinal tract can lead to long-term impacts in development and overall human health. Keystone species, includingBacteroides spp., play a crucial role in maintaining the structure, diversity, and function of the intestinal ecosystem. However, the process by which a defined and resilient community is curated and maintained during early life remains inadequately understood. Here, we show that a single sialidase, NanH, inBacteroides fragilismediates stable occupancy of the intestinal mucosa and regulates the commensal colonization program during the first weeks of life. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. After examining the dynamics between pioneer gutBacteroidesspecies in the murine gut, we discovered that NanH enables vertical transmission from dams to pups and promotesB. fragilisdominance during early life. Furthermore, we demonstrate that NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and the microbiota mediated through host-derived glycans to promote stable intestinal colonization.