Microbial-derived tryptophan metabolites in the infant gut associate with increased risk of asthma following cesarean section.

Delivery by cesarean section (CS) is a risk factor for childhood asthma and a strong determinant of the early-life gut microbiome. It has been reported that a CS-perturbed gut microbiome plays a mediating role in the association between CS and asthma risk. However, the underlying mechanisms remain unclear. Here, using deeply phenotyped participants in the Canadian birth cohort (CHILD), we characterized the CS microbial composition at 3 months and 1 year of age using machine learning models and described the perturbation using CS scores. The association between CS and the gut microbiota composition was more pronounced at 3 months (area under the curve (AUC) = 0.78) and attenuated at age 1 year (AUC = 0.60). An increased asthma risk at age 5 years was associated only with 1-year CS microbial scores (Odds ratio 1.41, P = 0.004; adjusted odds ratio 1.30, P = 0.034), consistent with our previous work. Extending this, we identified metabolic imbalances associated with 1-year CS microbial scores, marked by elevated tryptophan metabolites in the stool metabolome. These results replicate our previous findings about the mediating role of the 1-year CS microbial signature in the association between CS and asthma risk from the Danish COPSAC2010 cohort, and provide new insight into the underlying mechanism of host-microbe interaction following cesarean section.