Germs and genes: What affects childhood allergic rhinitis?

Recent research has found that bacterial richness in the upper airways during very early life alters epigenetic markings in nasal epithelium DNA. These changes persist until later childhood and may contribute to allergic rhinitis (AR).

“[O]ur study supports the view that interventions for modulating microbial composition, as early as the first week of life, could have a significant impact on both the quality of life for people and the economic burdens of nations associated with allergic diseases throughout the world,” the researchers said.

DNA methylation (DNAm) in nasal mucosal cells at 6 years of age was assessed in 468 children who participated in the Copenhagen Prospective Studies on Asthma in Childhood cohort. A total of 956 CpG sites were differentially methylated in AR; of these, 78 percent (n=741) saw less methylation. [J Allerg Clin Immunol 2020;146:1358-1366]

In subsequent analysis, 792 differentially methylated CpG sites (82 percent) formed three modules of correlated, comethylated sites. All three modules were associated with AR, though only one, called the blue module, was significantly linked to maternal rhinitis (p=0.041).

In addition, 46.5 percent of the sites under the blue module were more methylated in children with AR. Sites in this module were also correlated with an upregulation of expression of genes related to the bacterial invasion of epithelial cells, suggesting potential involvement in or impact of microbial exposures.

The researchers then looked at the upper airway microbiota of the participants. They found that children with AR at age 6 years had significantly lower flora richness at age 1 week (p=0.0079). Shannon diversity index at age 1 month was likewise suppressed in these children (p=0.045). No such differences were reported at 3 months of age.

Logistic regression was then performed to determine whether or not DNAm mediated microbiota richness at infancy and AR during childhood.

Initially controlling for only sex and read counts, the researchers confirmed a significant link between richness and eventual AR development (β, –1.12, 95 percent confidence interval [CI], –2.28 to –0.24; p=0.041).

However, additional adjustments for the blue module weakened this interaction by 61 percent and ultimately attenuated its significance (β, –0.58, 95 percent CI, –1.70 to 0.77; p=0.53). This indicated that the DNAm patterns described by the blue module explained more than half of the effect of bacterial richness in the upper airway during early life on AR in childhood.

“To our knowledge, this study is the first to show a longitudinal connection between microbiota and DNAm profiles in the upper airways, indicating lasting microbial effects on epigenetic patterns in the development of AR,” the researchers said. “These results suggest both that DNAm changes may be a persistent global marker of early-life exposures and that effects of methylation changes on gene expression are present in later childhood.

“Taken together these observations may reflect coordinated effects of DNAm patterns on gene expression that are associated with the development of AR,” they added.