Mutualistic interactions between Escherichia coli and Bifidobacterium bifidum enable degradation of human milk oligosaccharides in healthy infants

The development of the human gut microbiota during infancy is marked by frequent colonization of Enterobacteriaceae, a bacterial family notoriously associated with various diseases. Yet, despite their prominence in the absence of illness, their exact ecological role during healthy maturation of the infant gut remains poorly explored. Here, we analyse longitudinal stool samples from healthy, term-born, breastfed neonates (n=41) at two, six, and eleven months post-delivery, as well as microbiota of related mothers (n=30) with shotgun metagenomic sequencing, complemented by novel computational approaches and experimentation. Strain-resolved profiling indicates that dominant Bifidobacterium are frequently shared between infants and parenting mothers, while Escherichia coli originate from other sources, yet often persist within individuals. Despite their ecological differences, these genera co-exist, and both display evolutionary adaptations related to the utilization of human milk oligosaccharide (HMO) degradation products. 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 the cooperative degradation of 2′-fucosyllactose (2′FL), the predominant HMO. In turn, the liberated monosaccharides support E. coli proliferation and niche occupation. These findings reveal a fundamental cross-feeding interaction during development of healthy infant gut microbiota.