Human milk oligosaccharide mediates mutualism between Escherichia coli and Bifidobacterium bifidum

Infant gut microbiota development involves frequent colonization by Enterobacteriaceae , particularly Escherichia coli , yet their ecological role in healthy infants is unclear. Here, we analyse longitudinal stool samples from healthy, term-born, breastfed infants (n = 41) and related mothers (n = 30) using shotgun metagenomics and novel computational approaches. Strain-resolved profiling indicates that Bifidobacterium species are frequently shared within families, whereas E. coli derive from external sources, but often persist within individuals. Despite differing ecological strategies, these genera co-exist and share evolutionary adaptations related to lactose acquisition in the infant gut. In vitro, we demonstrate that interactions between E. coli and Bifidobacterium bifidum are mutualistic in co-culture, where E. coli supplies cysteine to its auxotrophic partner, facilitating cooperative degradation of 2′-fucosyllactose, the predominant human milk oligosaccharide. In turn, the liberated monosaccharides sustain E. coli growth, highlighting a cooperative cross-feeding interaction that may contribute to regulating E. coli abundance within the infant host.