Early life bacteria and sibling exposure associate with restoration of the infant gut microbiome after cesarean section

Long-term gut microbiome perturbation following Cesarean section (CS) delivery has been associated with an increased risk of developing childhood asthma. Whether such CS-associated microbiome composition can be modulated by environmental exposures or ecological interactions, and thereby mitigate disease risk, is unclear. In the COPSAC₂₀₁₀ birth cohort (N = 700), we develop a restoration score quantifying the degree to which the 1-year gut microbiome resembled that of vaginally delivered infants. We identify predictors of this restoration score in the 1-week gut microbiome. In addition, having older siblings is linked to a higher restoration score, mediated by increased abundances of restoration-associated bacteria. The restoration score, including association with delivery mode, older siblings and later asthma as well as early bacterial drivers, is successfully replicated in the independent Canadian birth cohort, CHILD. These insights suggest that specific early-life bacteria and sibling exposure may support microbiome restoration and confer protective effects against asthma risk.