A metabolite-dependent mechanism by which Bifidobacterium animalis subsp. lactis promotes Bacteroides colonization.

Prokaryote-prokaryote symbiotic relationships influence interactions within microbial communities, affecting colonization, survival, and organization. Unlike competition, consortium species facilitate growth via metabolite cross-feeding. This study explored interactions between two early human gut colonizers: partially aerotolerant Bifidobacterium spp. and strict anaerobic Bacteroides spp., using omics techniques. Promotion of Bacteroides spp. growth by Bifidobacterium animalis subsp. lactis was demonstrated through co-culture experiments in anaerobic conditions. Metabolomic analysis revealed over 150 unique metabolites present in B. animalis subsp. lactis supernatants are absent in other Bifidobacterium species, including 3-hydroxycapric acid, D-alanyl-D-alanine, 2-isopropylmalic acid, and D-glucose 2-phosphate. These compounds served as nutritional substrates, including carbon and nitrogen sources, significantly enhancing Bacteroides spp. growth. In murine models, early colonization by B. animalis subsp. lactis consolidated Bacteroides fragilis colonization (1.7 × 104 to 9.7 × 106 copy number/g fecal sample) by providing these metabolites as a niche. These findings highlight B. animalis subsp. lactis plays a critical role in gut colonization of Bacteroides spp. via its exclusive metabolic profile, offering insights into partitioned metabolic activity within gut communities and emphasizing the importance of specific metabolites in early microbial establishment.