Metagenomic-based network analysis reveals the importance of vitamin cross-feeding in marine microbial assemblages

Vitamins play a fundamental role in microbial metabolism and interactions, yet their scarcity in marine environments and the limited ability for de novo synthesis of some vitamins often leads to metabolic dependencies and cross-feeding among microbial taxa. Using a decade-long time-series metagenomics dataset from the Blanes Bay Microbial Observatory (BBMO), we investigated the role of vitamin biosynthesis in structuring the seasonal marine microbial interactions among prokaryotes and eukaryotes. Gene co-occurrence analysis revealed that vitamin-related metabolism had the highest number of associations among all metabolic pathways, underscoring the potential role of vitamins in microbial interactions. Metagenome-assembled genome (MAG) co-occurrence analysis further identified the prokaryotic biosynthesis of cobalamin (B ₁₂ ) and thiamine (B ₁ ) as key mediators of these associations. Rather than between complete vitamin synthesizers and auxotrophs, the main associations were found between partial synthesizers, suggesting that vitamer cross-feeding may represent an essential microbial interaction in sustaining vitamin biosynthesis throughout the year. While complete cobalamin synthesizers dominate in summer, partial synthesizers and lower-ligand activators are more prevalent in winter, driving cross-feeding interactions. In contrast, thiamine biosynthesis is more widespread, with complete synthesizers peaking in winter. The association strength, however, was maximum between prokaryotic vitamin producers and eukaryotes, highlighting the dependence of eukaryotes on bacterial vitamin production. These results provide novel insights into seasonal metabolic interdependencies, emphasizing the ecological significance of vitamin biosynthesis in marine ecosystems.