Unique ecology of co-occurring functionally and phylogenetically undescribed species in the infant oral microbiome

Abstract

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. Author SummaryWe investigated how infant oral bacterial communities develop during their first six months of life, with the aim to understand which microbes colonize, how they establish themselves and why they succeed together. Using high throughput DNA sequencing techniques, we analyzed oral samples from 24 mother-infant pairs at one and six months after birth. We found two abundant, but previously unknown bacterial species (one Streptococcus and one Rothia) at six months of age. These bacteria consistently appear together across different babies, suggesting they may depend on each other for survival and growth. By reconstructing the genomes of these bacteria directly from our samples, we discovered specific genetic features that help explain their success in the infant mouth. Streptococcus carries genes that allow it to break down nutrients from breast milk. Rothia has genes that help it rapidly build cell membranes and protect against harmful molecules, while producing nutrients that Streptococcus needs. We predict these bacteria exchange key nutrients like malate and lysine, creating a mutually beneficial partnership. The bacteria seem to cooperate and are predicted to exchange key nutrients like malate and lysine which may help maintain a healthy oral environment by regulating acidity levels, potentially protecting against tooth decay.