Secretory IgA modifies the association between early-life gut microbiota trajectories and childhood nonatopic wheeze

Aims: Wheezing in childhood is common and evidence is accumulating for the role of the gut microbiome in the development of atopic wheeze. Changes to the early-life gut microbiota and secretory IgA (SIgA) production have been linked to childhood disease; however, their connection to nonatopic wheeze is unknown. The objectives of the present study were to evaluate the relationships between early-life gut microbiota trajectories, SIgA and childhood nonatopic wheeze. Methods: Early-life gut microbiota, SIgA and child outcome data were collected as part of the Canadian Healthy Infant Longitudinal Development (CHILD) cohort study on 1203 children. Gut microbiota trajectories were categorised as C1-C1, C1-C2, C2-C1 and C2-C2 based on low (cluster 1; C1) or high (cluster 2; C2) Bacteroides abundance in faecal samples collected at 3 and 12 months. SIgA was assessed in faecal samples at 3 months. Results: The main outcome was nonatopic wheeze before age 5 years (n=105). Logistic regression analysis showed the C1-C2 trajectory, of low Bacteroides abundance at 3 months but higher Bacteroides abundance at 12 months, to be associated with increased adjusted odds ratio (aOR) for nonatopic wheeze (aOR 1.74, 95% CI 1.13-2.67). This was further increased if the child was not exclusively breastfed and had high SIgA level in combination with the C1-C2 trajectory (OR 4.10, 95% CI 1.15-14.59). Conclusions: Nonatopic wheeze is associated with a depletion of Bacteroides in infancy, and in children not exclusively breastfed the risk is further increased among those with high endogenous SIgA levels. These results highlight the importance of the interplay between the gut microbiota and immune system development during critical periods in early life and how it is linked to nonatopic wheeze in childhood.