Interactions between host genetics and gut microbiome influence susceptibility to childhood asthma and lung function.

Abstract

The gut microbiome is thought to influence risk of childhood allergic diseases; however, the data on species-level links to childhood asthma and lung function are limited, and the role of host genetics in the gut-lung axis remains unclear. In a multicenter cross-sectional study of children with a history of bronchiolitis from the 35th Multicenter Airway Research Collaboration, we performed shotgun metagenomic profiling of stool samples obtained at age 6 years and examined associations of the gut microbiome with asthma prevalence and lung function. We also calculated polygenic risk scores (PRSs) of asthma and lung function to investigate the interaction between host genetics and the gut microbiome in relation to these traits. In the 300 children included for this study, 3 bacterial species (ie, Bacteroides vulgatus, Eisenbergiella massiliensis, and Butyricimonas virosa) were differentially associated with FEV₁ value and 4 bacterial species were differentially associated with ratio of FEV₁ value to forced vital capacity (FVC) (eg, Bifidobacterium longum) (false discovery rate [FDR] according to the R package MaAsLin < 0.25). Furthermore, host genetics-gut microbiome interaction analysis showed association of B vulgatus (FDR = 0.037) and Bacteroides uniformis (FDR = 0.037) with FEV₁/FVC ratio among children with a high FEV₁/FVC ratio PRS. Additionally, Ruminococcus bromii (FDR = 0.067) and Alistipes indistinctus (FDR = 0.13) were suggested to have protective associations with asthma, specifically in children with a high asthma PRS, indicating that host genetics can modulate the effect of the gut microbiome on these respiratory outcomes. By applying the metagenomic approach to a multicenter cohort of children with a history of bronchiolitis during infancy, this study suggests potential interplay of host genetics with the gut microbiome, as well as their integrated relationship with childhood asthma and lung function.