Emergent roles of infant gut microbes during the utilization of human milk oligosaccharides

Abstract

Bifidobacterium spp. are representative species of the infant gut microbiome. Human milk oligosaccharides (HMOs) are complex carbohydrates in breast milk, guiding gut microbiome assembly by establishing complex microbial interactions. Here, a synthetic community of seven infant gut microbes was subjected to single species dropouts in bioreactors using three HMOs. Substrate use, acid production, biomass, and metatranscriptomics revealed that B. bifidum was critical for degradation product formation and supporting cross-feeding. Removing B. longum subsp. infantis, known for intracellular HMO use, accelerated global growth and HMO consumption, suggesting competitive interactions. Some dropouts led to the accumulation of sialic acid, fucose, or lactose. Metatranscriptomics showed niche expansion, upregulated central metabolism and cross-feeding dependencies when certain species were removed. Modeling highlighted that HMO degradation rates strongly influence community dynamics. Overall, this study identifies key ecological roles in infant gut microbes and deepens our understanding of how HMOs shape microbiota assembly and function.