The impact of the COVID-19 pandemic and associated lifestyle changes on early-life microbiome development: a natural experiment

The COVID-19 pandemic triggered rapid, population-wide behavioral and environmental changes, offering a unique natural experiment to study how early-life microbiome development responds to abrupt shifts in social and hygiene-related exposures.Using longitudinal data from 139 infants in the Dutch LucKi Gut study, we compared gut microbiome development in fecal samples collected before and during the pandemic. Whole metagenome sequencing of 808 stool samples was performed across nine time points in the first 14 months of life. An exposure index (EI) capturing variation in household-level pandemic-related behaviors was constructed to quantify variations in social distancing, lifestyle and hygiene measures.Microbial richness and diversity increased with age, following established developmental trajectories. However, from 6 months onward, the COVID-19 pandemic independently shaped gut microbial composition, explaining up to 2.7% of variation by 11 months of age. Forty-four species were differentially abundant in pandemic-era samples, including depletion of Gordonibacter pamelaeae and several Actinomyces species. Notably, greater environmental exposure (higher EI scores) was associated with lower abundance of G. pamelaeae, a microbe implicated in bile acid and immunomodulatory metabolism.This is the first longitudinal whole-genome sequencing study to demonstrate that pandemic-related behavioral changes measurably altered infant gut microbiota maturation. These findings highlight the sensitivity of microbiome development to societal-level environmental disruptions and suggest that early-life microbial exposures, modulated by hygiene and social behavior, may carry long-term implications for child health.