Sex differences in the oral microbiome, host traits, and their causal relationships

Xiaomin Liu; Xin Tong; Zhuye Jie; Jie Zhu; Liu Tian; Qiang Sun; Yanmei Ju; Leying Zou; Haorong Lu; Xuemei Qiu; Qiang Li; Yunli Liao; Heng Lian; Yong Zuo; Xiaomin Chen; Weiqiao Rao; Yan Ren; Yuan Wang; Jin Zi; Rong Wang; Xun Xu; Huanming Yang; Jian Wang; Yang Zong; Weibin Liu; Yong Hou; Xin Jin; Liang Xiao; Karsten Kristiansen; Huijue Jia; Tao Zhang

doi:10.1016/j.isci.2022.105839

Sex differences in the oral microbiome, host traits, and their causal relationships

iScience. 2022 Dec 22;26(1):105839. doi: 10.1016/j.isci.2022.105839. eCollection 2023 Jan 20.

Authors

Xiaomin Liu^{1

2}, Xin Tong², Zhuye Jie^{2

3}, Jie Zhu², Liu Tian², Qiang Sun^{2

4}, Yanmei Ju², Leying Zou², Haorong Lu⁵, Xuemei Qiu², Qiang Li², Yunli Liao², Heng Lian², Yong Zuo², Xiaomin Chen², Weiqiao Rao², Yan Ren², Yuan Wang², Jin Zi², Rong Wang², Xun Xu², Huanming Yang^{2

6

7}, Jian Wang^{2

6

7}, Yang Zong², Weibin Liu², Yong Hou², Xin Jin², Liang Xiao², Karsten Kristiansen^{2

3}, Huijue Jia^{2

5}, Tao Zhang^{2

3}

Affiliations

¹ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
² BGI-Shenzhen, Shenzhen 518083, China.
³ Department of Biology, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen, Denmark.
⁴ Department of Statistical Sciences, University of Toronto, Toronto, ON M5G 1Z5, Canada.
⁵ China National Genebank, BGI-Shenzhen, Shenzhen 518120, China.
⁶ BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China.
⁷ James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.

Abstract

The oral microbiome has been implicated in a growing number of diseases; however, determinants of the oral microbiome and their roles remain elusive. Here, we investigated the oral (saliva and tongue dorsum) metagenome, the whole genome, and other omics data in a total of 4,478 individuals and demonstrated that the oral microbiome composition and its major contributing host factors significantly differed between sexes. We thus conducted a sex-stratified metagenome-genome-wide-association study (M-GWAS) and identified 11 differential genetic associations with the oral microbiome (p _{sex-difference} < 5 × 10^-8). Furthermore, we performed sex-stratified Mendelian randomization (MR) analyses and identified abundant causalities between the oral microbiome and serum metabolites. Notably, sex-specific microbes-hormonal interactions explained the mostly observed sex hormones differences such as the significant causalities enrichments for aldosterone in females and androstenedione in males. These findings illustrate the necessity of sex stratification and deepen our understanding of the interplay between the oral microbiome and serum metabolites.

Keywords: Microbial metabolism; Microbiome; Oral microbiology.