Association between the ABCC11 gene polymorphism-determined earwax properties and external auditory canal microbiota in healthy adults

Abstract

The concept of genome-microbiome interactions, in which the microenvironment determined by host genetic polymorphisms regulates the local microbiota, is important in the pathogenesis of human disease. In otolaryngology, the resident bacterial microbiota is reportedly altered in non-infectious ear diseases, such as otitis media pearls and exudative otitis media. We hypothesized that a single-nucleotide polymorphism in the ATP-binding cassette sub-family C member 11 (ABCC11) gene, which determines earwax properties, regulates the ear canal microbiota. We analyzed ABCC11 gene polymorphisms and ear canal microbiota in healthy individuals to understand the relationship between genome-microbiome interactions in the ear canal. The study included 21 subjects who were divided into two groups: 538GA (9) and 538AA (12). Staphylococcus auricularis and Corynebacterium spp. were observed in the 538GA group, whereas Methylocella spp. was observed in the 538AA group. PICRUSt analysis revealed significant enrichment of certain pathways, such as superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation, chlorosalicylate degradation, mycothiol biosynthesis, and enterobactin biosynthesis in the GA group, whereas allantoin degradation IV (anaerobic), nitrifier denitrification, starch degradation III, L-valine degradation I, and nicotinate degradation I were significantly enriched in the AA group. The ABCC11 gene polymorphism regulates the composition of the ear canal microbiota and its metabolic pathways. This study revealed a genome-microbiome interaction within the resident microbiota of the external auditory canal that may help to elucidate the pathogenesis of ear diseases and develop novel therapies.

Importance: The ABCC11 gene polymorphism, which determines earwax characteristics, regulates the composition of the ear canal microbiota and its metabolic pathways. We determined the presence of genome-microbiome interactions in the resident microbiota of the ear canal. Future studies should focus on ABCC11 gene polymorphisms to elucidate the pathogenesis of ear diseases and develop therapeutic methods.

Keywords: ABCC11; ear canal; genome-microbiome interaction; human microbiome.

Fig 1

Association of ABCC11 gene polymorphisms with the bacterial microbiota of the external auditory canal beta diversity in the ear canal bacterial microbiota of healthy subjects (nine in the AA group and 12 in the GA group) analyzed using QIIME2.

Fig 2

Relative abundance of ear canal bacteria in each subject. (a). Proportion of bacteria at the discernible genus level in the ear canal of each subject. Names of the bacteria are presented in the bar graph. (b). Bar graph demonstrating the microbiota composition in each group, where the sum of all the bacteria observed in more than 0.1% of the cases in each group is summed to 100% (Fig. 2).

Fig 3

Differences in the indigenous bacteria of the ear canal owing to ABCC11 gene polymorphisms (a). Comparison of the relative abundance of Methylocella spp. in the AA and GA groups. (b). Comparison of the relative abundance of Staphylococcus auricularis and Corynebacterium spp. in the AA and GA groups.

Fig 4

Differences in resident bacteria in the ear canal by sex, age, and ear-cleaning habits (a). Comparison of the relative abundance of Streptococcus spp. by sex. (b). Comparison of the relative abundance of Streptococcus spp. by age. Simple linear regression model was used to compare age at sample collection and proportion of each microbiota. Pearson correlation coefficients were calculated to assess relationships among variables. (c). Comparison of the relative abundance of Malassezia spp. by ear-cleaning habits. One-way analysis of variance (ANOVA) with Tukey–Kramer’s HSD test was used to compare ear-cleaning habits and the proportions of each microbiota.