Influence of environmental factors on early-life gut microbial trajectories and maturation

Background: The early-life gut microbiome undergoes rapid, dynamic succession that influences immune maturation and long-term health. However, understanding how environmental exposures shape development requires biologically-informed longitudinal studies that capture community-scale changes beyond infancy. Results: Using 16S rRNA gene sequencing data from the COPSAC ₂₀₁₀ birth cohort (n = 695), we identified four distinct microbial trajectories—each reflecting coherent successional stages—based on abundance peaks spanning the first six years of life. Key early-life exposures—including delivery mode, siblings, household pets, and living environment—were among those significantly associated with differences in both the timing and composition of these microbial trajectories, including shifts in dominant genera. Cesarean delivery was linked to prolonged dominance of early colonizers and delayed transition to more mature microbial communities, whereas exposure to siblings and rural environments accelerated microbial maturation. Validation in the independent MAMI cohort (n = 199) confirmed the generalizability of this framework across geographic and cultural contexts. Conclusions: Microbial succession in early life follows structured yet environmentally modifiable trajectories. These findings provide a framework for identifying critical windows of opportunity to promote gut microbial maturation and potentially influence long-term health outcomes.