Resource sharing of an infant gut microbiota synthetic community in combinations of human milk oligosaccharides

Quickly after birth, the gut microbiota is shaped via species acquisition and resource pressure. Breastmilk, and more specifically, human milk oligosaccharides are a determining factor in the formation of microbial communities and the interactions between bacteria. Prominent human milk oligosaccharide degraders have been rigorously characterized, but it is not known how the gut microbiota is shaped as a complex community. Here, we designed BIG-Syc, a synthetic community of 13 strains from the gut of vaginally born, breastfed infants. BIG-Syc replicated key compositional, metabolic, and proteomic characteristics of the gut microbiota of infants. Upon fermentation of a 4 and 5 human milk oligosaccharide mix, BIG-Syc demonstrated different compositional and proteomic profiles, with Bifidobacterium infantis and Bifidobacterium bifidum suppressing one another. The mix of 5 human milk oligosaccharides resulted in a more diverse composition with dominance of B. bifidum, whereas that with 4 human milk oligosaccharides supported the dominance of B. infantis, in 4 of 6 replicates. Reintroduction of bifidobacteria to BIG-Syc led to their engraftment and establishment of their niche. Based on proteomics and genome-scale metabolic models, we reconstructed the carbon source utilization and metabolite and gas production per strain. BIG-Syc demonstrated teamwork as cross-feeders utilized simpler carbohydrates, organic acids, and gases released from human milk oligosaccharide degraders. Collectively, our results showed that human milk oligosaccharides prompt resource-sharing for their complete degradation while leading to a different compositional and functional profile in the community. At the same time, BIG-Syc proved to be an accurate model for the representation of intra-microbe interactions.