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Sex differences exist in the commensal microbiota that impact on multiple physiological processes in the host. Here, we examined the mechanism by which the sex differences are formed. In addition to the epithelial ductal cell, the acinar cell mass in the submandibular gland was associated with androgen-androgen receptor (AR) signaling. Sex differences in the formation of submandibular mucin 10 (MUC10) were identified using SDS-PAGE. Neuraminidase treatment, which hydrolyzes terminal sialic acid, influenced the mobility shift of MUC10. Androgen-AR signaling negatively regulated ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (St3gal1) and St3gal4 in the submandibular gland. There was a trend and significant sex differences in alpha-diversity (Shannon, P = .09) and beta-diversity (unweighted UniFrac) in oral microbiota composition, respectively. Some female-preferring bacteria including Akkermansia muciniphila can assimilate mucin by degrading terminal sialic acids. Our results indicate that androgen-AR signaling suppresses ST3GAL1 and ST3GAL4, which can influence sex differences in commensal microbiota composition.
