Sex hormones, sex chromosomes, and microbiota: identification of Akkermansia muciniphila as an estrogen-responsive bacterium
Anil Sakamuri, Pritam Bardhan, Ramakumar Tummala, Franck Mauvais‐Jarvis, Tao Yang, Bina Joe, Benard O. Ogola
Abstract
Microbiota composition is known to be linked to sex. However, separating sex hormones and sex chromosome roles in gut microbial diversity is yet to be determined. To investigate the sex chromosome role independent of sex hormones, we used the four-core genotype mouse model. In this mouse model, males with testes and females with ovaries have XX or XY sex chromosome complement. In gonadectomized four-core genotype mice, we observed a significant decrease in the levels of estradiol ( P < 0.001) and progesterone ( P < 0.03) in female and testosterone ( P < 0.0001) in male mice plasma samples. Independent of sex chromosome complement, microbial α diversity was increased in gonadectomized female but not male mice compared to sex-matched gonad-intact controls. β diversity analysis showed separation between male ( P < 0.05) but not female XX and XY mice. Importantly, Akkermansiamuciniphila was less abundant in gonadectomized compared to gonadal intact female mice ( P < 0.0001). In the presence of β-estradiol, A.muciniphila growth exponentially increased, providing evidence for the identification of a female sex hormone-responsive bacterium ( P < 0.001).