青年における鼻内細菌叢とエピゲノムの相互作用

The respiratory microbiome, including that of the nasal cavity, is involved in host defense and airway pathophysiology. Interactions of the microbiome with the host immune system may impact health and disease susceptibility through changes in the epigenome. In this study, we aimed to analyze cross-sectional associations of nasal microbiome composition and the nasal epigenome among adolescents in the Project Viva cohort (N = 372, mean age: 13.0 years). We collected nasal swabs from anterior nares, profiled the microbiome by 16 S rRNA gene sequencing, and grouped samples into 6 clusters using partitioning around medoids. Nasal cell DNA methylation was measured with the Illumina MethylationEPIC BeadChip. In an epigenome-wide association study, we tested for associations of microbiome cluster assignment and DNA methylation using robust linear models adjusting sociodemographics, season, batch, and surrogates of cell type composition. Among significant loci, we conducted differential abundance analysis to identify individual bacterial genera associated with DNA methylation levels.

A total of 45 loci had differential methylation between two or more microbiome clusters (p_Bonferroni< 0.05). Methylation differences between clusters ranged from 0.20 to 12.45% (median = 0.95%). Differentially methylated loci were near genes related to asthma (ITPR2, MAPK1), lung function (FKBP11), mitochondrial function (MRPL20, SPTBN1), inflammation (C3), and immune function (N4BP3, EIF5). The abundance of individual taxa, particularly Propionibacterium, was associated with methylation at 15 of these loci (FDR < 0.05). In addition, we found greater Corynebacterium abundance was associated with lower nasal epigenetic aging (FDR < 0.05).

Our findings support the hypothesis that the nasal microbiome is associated with small-to-modest variation in the nasal epigenome. Future research is needed to investigate how the relationship between the nasal microbiome and epigenome is impacted by environmental exposures, as well as the health effects of microbial and epigenetic variation in early life and across the life course.