Milk and mucin glycans orchestrate a synthetic infant gut microbiota structure

Glycans are crucial for infant gut microbiota development. Human milk contains prebiotic human milk oligosaccharides (HMOs) that stimulate gut microbes. Simultaneously, the glycan-rich mucus layer develops and attracts mucin glycan-degrading bacteria. As HMOs and mucin are degraded by homologous enzymes, bacterial glycan-degrading abilities overlap. However, less is known about how infant gut microbial communities form when both types of glycans are available. To study this, we created a synthetic community with specialist glycan degraders and cross-feeders from the infant gut (BabyBac). We evaluated it in different in vitro conditions including combinations of diet-derived [HMOs, galactooligosaccharides (GOS), and fructooligosaccharides (FOS)] and mucus glycans. Glycan combinations significantly affected the community composition and metabolic output. The glycan type affected the overall community, with mucin and HMOs being the top drivers of variation. HMOs favoured glycan degraders and cross-feeders, whereas mucin glycan degrader Akkermansia muciniphila was outcompeted. Conversely, when mucin was present, A. muciniphila thrived. Addition of mucin monomers and 2'-FL to GOS/FOS did not reinstate A. muciniphila abundance. This suggests that A. muciniphila cannot compete with infant-related bacteria without the complete mucin structure. Overall, our findings suggest that the interplay between dietary and mucus glycans creates niche differentiation in the infant gut microbiota.