A newborn derived monoclonal IgM antibody selectively modulates microbial metabolism in the gut

Metabolism and gut microbiota are essential for newborn health, influencing immune function, energy balance, and growth. Breast milk provides IgA, crucial for shaping gut microbiota in infants. In non-breastfed newborns, we observe the presence of IgM antibodies that can recognize various bacteria, influence bacterial clustering, and alter bacterial metabolism, such as carbon source utilization in vitro within small bacterial communities. Based on these findings, we developed a monoclonal IgM, M291, derived from a newborn-B cell, which mimics naturally occurring antibodies and could serve as a surrogate tool to modulate intestinal bacterial functions and metabolism. Oral administration of M291 alters the metabolome of germ-free mice colonized with a defined bacterial consortium or an infant gut microbiota, by modulating the bacterial transcriptome, while maintaining microbial abundance and diversity. This study establishes proof of concept for the design and application of newborn-derived antibodies to modulate microbial and host metabolism, including lipid metabolism and bile acid secretion, without significantly altering microbiota composition.