Altered IgA Response to Gut Bacteria Is Associated with Childhood Asthma in Peru

Alterations in gut microbiota in early life have been associated with the development of asthma; however, the role of gut bacteria or the IgA response to gut bacteria in school-aged children with asthma is unclear. To address this question, we profiled the microbial populations in fecal and nasal swab samples by 16S rRNA sequencing from 40 asthma and 40 control children aged 9-17 y from Peru. Clinical history and laboratory evaluation of asthma and allergy were obtained. Fecal samples were analyzed by flow cytometry and sorted into IgA⁺ and IgA^- subsets for 16S rRNA sequencing. We found that the fecal or nasal microbial 16S rRNA diversity and frequency of IgA⁺ fecal bacteria did not differ between children with or without asthma. However, the α diversity of fecal IgA⁺ bacteria was decreased in asthma compared with control. Machine learning analysis of fecal bacterial IgA-enrichment data revealed loss of IgA binding to the Blautia, Ruminococcus, and Lachnospiraceae taxa in children with asthma compared with controls. In addition, this loss of IgA binding was associated with worse asthma control (Asthma Control Test) and increased odds of severe as opposed to mild to moderate asthma. Thus, despite little to no change in the microbiota, children with asthma exhibit an altered host IgA response to gut bacteria compared with control participants. Notably, the signature of altered IgA responses is loss of IgA binding, in particular to members of Clostridia spp., which is associated with greater severity of asthma.