Pucci, N.; Kaan, A. M.; Ujcic-Voortman, J.; Verhoeff, A. P.; Zaura, E.; Mende, D.

Early-life oral microbiome development is a complex community assembly process that influences long-term health outcomes. Nevertheless, microbial functions and interactions driving these ecological processes remain poorly understood. In this study, we analyze oral microbiomes from a longitudinal cohort of 24 mother-infant dyads at 1 and 6 months postpartum using shotgun metagenomics. We identify two previously undescribed Streptococcus and Rothia species to be among the most prevalent, abundant and strongly co-occurring members of the oral microbiome of six-month-old infants. To explore the underlying genomic traits enabling this unique lifestyle, we leveraged metagenome-assembled genomes (MAGs) and genome-scale metabolic models (GEMS). Comparative analyses revealed specific genomic and functional characteristics relative to other closely related species and highlighted unique functional features, including genes encoding adhesins and carbohydrate-active enzymes (CAZymes). The observed co-occurrence patterns were further supported by predicted metabolic interactions within a network of co-occurring oral taxa. Metabolic modeling identified potential exchange of key nutrients, particularly malate and lysine, between these species, suggesting metabolic cross-feeding interactions that may explain their co-occurrence across infant oral microbiomes. Overall, this study provides key insights into the functional adaptations and microbial interactions shaping early colonization in the oral cavity.