Altered IgA responses to gut bacteria is associated with asthma in Peru

Rationale: 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.Objectives: To determine whether children with and without asthma from Peru differ in their gut microbiota or their IgA response to gut bacteria.Methods: Clinical history and evaluation was performed on 40 asthma and 40 control children aged 9 to 17 years. Fecal and nasal swab samples were collected and analyzed by 16S rRNA sequencing. Fecal samples were analyzed by flow cytometry and sorted into IgA+ and IgA– subsets for 16S rRNA sequencing.Results: Fecal or nasal microbial 16S rRNA diversity and frequency of IgA+ fecal bacteria did not differ between children with or without asthma. However, the alpha diversity of fecal IgA+ bacteria was decreased in asthma compared to 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 to 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.Conclusions: 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.