Distinct Gene Expression Profiles in Colonic Organoids from Normotensive and the Spontaneously Hypertensive Rats

Hypertension is associated with gut bacterial dysbiosis and gut pathology in animal models and people. Butyrate-producing gut bacteria are decreased in hypertension. RNA-seq analysis of gut colonic organoids prepared from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to test the hypothesis that impaired interactions between the gut microbiome and gut epithelium are involved and that these would be remediated with butyrate supplementation. Gene expressions in immune responses including antigen presentation and antiviral pathways were decreased in the gut epithelium of the SHR in organoids and confirmed in vivo; these deficits were corrected by butyrate supplementation. Deficits in gene expression driving epithelial proliferation and differentiation were also observed in SHR. These findings highlight the importance of aligned interactions of the gut microbiome and gut immune responses to blood pressure homeostasis.