Priority effects, nutrition and milk glycan-metabolic potential drive subspecies dynamics in the infant gut microbiome.

BACKGROUND

The initial colonization of the infant gut is a complex process that defines the foundation for a healthy microbiome development. is one of the first colonizers of newborns' gut, playing a crucial role in the healthy development of both the host and its microbiome. However, exhibits significant genomic diversity, with subspecies ( subsp. and subsp. ) displaying distinct ecological and metabolic strategies including differential capabilities to break down human milk glycans (HMGs). To promote healthy infant microbiome development, a good understanding of the factors governing infant microbiome dynamics is required.

METHODOLOGY

We analyzed newly sequenced gut microbiome samples of mother-infant pairs from the Amsterdam Infant Microbiome Study (AIMS) and four publicly available datasets to identify important environmental and bifidobacterial features associated with the colonization success and succession outcomes of subspecies. Metagenome-assembled genomes (MAGs) were generated and assessed to identify characteristics of subspecies in relation to early-life gut colonization. We further implemented machine learning tools to identify significant features associated with subspecies abundance.

RESULTS

subsp. was the most abundant and prevalent gut at one month, being replaced by subsp. at six months of age. By utilizing metagenome-assembled genomes (MAGs), we reveal significant differences between and within subspecies in their potential to break down HMGs. We further combined strain-tracking, meta-pangenomics and machine learning to understand these abundance dynamics and found an interplay of priority effects, milk-feeding type and HMG-utilization potential to govern them across the first six months of life. We find higher abundances of subsp. in the maternal gut microbiome, vertical transmission, breast milk and a broader range of HMG-utilizing genes to promote its abundance at one month of age. Eventually, we find subsp. to be replaced by subsp. at six months of age due to a combination of nutritional intake, HMG-utilization potential and a diminishment of priority effects.

DISCUSSION

Our results establish a strain-level ecological framework explaining early-life abundance dynamics of subspecies. We highlight the role of priority effects, nutrition and significant variability in HMG-utilization potential in determining the predictable colonization and succession trajectories of subspecies, with potential implications for promoting infant health and well-being.