Beyond the gastrointestinal tract: oral and sex-specific skin microbiota are associated with hypertension in rats with genetic disparities

Abstract

Current knowledge of the link between microbiota and hypertension is limited to the gut. Besides the gut, oral cavity and skin are other locations where sodium chloride (NaCl) is in direct contact with microbiota. Although oral nitrate-reducing bacteria generate nitric oxide, which leads to vasodilation and lowering of blood pressure (BP), the skin excretes sodium via sweat glands and is an important site for sodium and BP homeostasis. However, knowledge on the contributions of oral and skin microbiota to BP regulation, is limited. Therefore, the current study was conducted to compare the tripartite relationship between site, sex, and genetic effects on the composition of oral, skin, and gut microbiota impacting hypertension. Microbiota were profiled from the oral cavity, skin, and feces of both male and female hypertensive Dahl salt-sensitive (S) and congenic rats with genomic substitutions on rat chromosomes (RNO) 1, 5, 9, and 10, demonstrating disparate BP effects. Sex-specific differences in b-diversity were observed only in skin microbiota. The most abundant taxa of the oral and skin microbiota were Actinobacteria and Cyanobacteria, respectively. Oral Actinobacteria were inversely associated with BP. Although the abun-dance of oral Actinobacteria was upregulated by the BP locus on RNO10 in both sexes, depletion of skin Cyanobacteria decreased the protection from hypertension in the RNO5 female, but not male, congenic strain. In conclusion, to our knowledge this is the first study to identify specific microbiota in sites other than gut as contributors to BP regulation. Notably, both oral Actinobacteria and skin Cyanobacteria were beneficial for lowering BP.