Gut microbial IgA coating in infants with traditional farming lifestyle and urban infants with allergic outcomes

Background The sharp increase in prevalence of atopic disease suggests a role for environmental factors, such as the microbiome. Here, we study the impact of immunoglobulin A (IgA) coating of gut bacteria in infancy on allergic outcomes in two distinct populations: (1) an urbanized cohort of Rochester infants (ROC) enriched for allergies (prevalence of 40%) and (2) infants from a traditional, agrarian Old Order Mennonite (OOM) community with a low prevalence of allergies (less than 2%). Methods We performed immunoglobulin A sequencing (IgA-SEQ) on stool samples collected at an average of 6 months of life to assess gut microbiome IgA coating levels in 9 OOM and 21 ROC infants. Atopic outcomes were diagnosed throughout the first 2 years; 10 of the ROC infants were diagnosed with atopic dermatitis and/or food allergy, while none of the OOM infants were allergic. We also assessed human milk IgA-binding of taxa-derived protein antigens, as well as IgA binding to live bacterial cell cultures. Results Gut microbiome composition was dominated by Bifidobacterium , followed by Ruminococcus , Enterobacteriaceae, and Blautia . Higher IgA coating of P. melaninogenica and Pasteurellaceae were associated with allergic outcomes and higher coating of R. gnavus was observed in non-allergic infants. IgA coating levels of Atopobium , Bifidobacterium , and Coprococcus were positively associated with infant age, and coating levels of Corynebacterium associated negatively with infant age. In non-allergic infants, IgA coating of Clostridium was decreased, while in allergic infants, IgA coating of Corynebacterium was decreased. Furthermore, breastfeeding was associated with higher levels of fecal IgA in infancy, and IgA-binding capacity to B. infantis , a keystone infant commensal, was subsequently assessed using in vitro experiments. Compared to the ROC cohort, milk from OOM mothers exhibited a higher level of IgA response to B. infantis and several other commensals. Surprisingly, IgA-binding to B. infantis was partially mediated by Fab-independent interactions through binding to glycosylated regions of immunoglobulins. Conclusion Differential gut microbial IgA coating may play a role in development of allergic diseases in infancy. Human milk from communities with low rates of allergic diseases exhibit higher IgA responses to infant commensals, including B. infantis .