Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

Abstract

The oral microbiota contains billions of microbial cells, which could contribute to diseases in many body sites. Challenged by eating, drinking, and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1915 individuals, for both the tongue dorsum (n = 2017) and saliva (n = 1915). We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 × 10−11). Four of the five associations were well replicated in an independent cohort of 1439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of host genome-microbiome associations including six genome-wide significant associations mutually validated between the two niches. As many of the oral microbiome-associated genetic variants lie near miRNA genes, we tentatively validated the potential of host miRNAs to modulate the growth of specific oral bacteria. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk scores dominated over oral microbiome in predicting risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

The Role of the Intestine in the Development of Hyperuricemia

“…In keeping with in vitro and animal studies, data from large-scale metagenome genome-wide association studies (mgGWAS) for the oral microbiome revealed unequivocal human genetic loci associated with the oral microbiome, including uric acid transporter SLC2A9. SLC2A9 showed a strong correlation with species-level clusters belonging to oribacterium and lanchnoanaerobaculum in tongue dorsum samples ( 83 ). A previous study reported that oral cavity and stool bacteria overlapped in more than 45% of subjects ( 84 ).…”

“…A previous study reported that oral cavity and stool bacteria overlapped in more than 45% of subjects ( 84 ). Interestingly, the tongue dorsum microbiota related gene SLC2A9 was correlated with the abundance of Bifidobacterium animalis in the gut ( 83 ). These results demonstrated that gut microbial diversity also has an impact on uric acid transporters.…”

Ecological Effects of Daily Antiseptic Treatment on Microbial Composition of Saliva-Grown Microcosm Biofilms and Selection of Resistant Phenotypes

“…For instance, microbial communities in saliva and subgingival biofilms were found to have distinct ethnicity profiles, and based on these results, it was even possible to identify the ethnicity of individuals from subgingival microbial signatures using a machine learning classifier ( Mason et al, 2013 ). Furthermore, a recent metagenome-wide association study found that human genetics account for at least 10% of oral microbiome compositions between different individuals, which may also explain the stable microbial composition within one single individual over time ( Liu et al, 2021 ).…”

Profile of the oral microbiota from preconception to the third trimester of pregnancy and its association with oral hygiene practices

“…The stability of the oral microbiota is dependent on both intrinsic host factors, such as the genetic composition of the host and aging [ 8 ]. It is also influenced by extrinsic host factors, such as drug use and lifestyle [ 9–11 ].…”