Gut Microbes · Available online 24 Jun 2026 · In press · DOI 10.1080/19490976.2026.2691346
Sachin Aryal, Blair Mell, Ramakumar Tummala, Ishan Manandhar, Sanjana Kumariya, Narendra Kondapalli, Beng San Yeoh, Wisdom Ahlidja, Oluwatosin Mautin Akinola, Sudhan Pachhain, Pritam Bardhan, Piu Saha, Sareh Zeydabadinejad, Islam Osman, Charles Thodeti, Tao Yang, Matam Vijay-Kumar, Lavanya Reddivari, Bina Joe
Gut microbiota and bile acids are increasingly recognized to regulate blood pressure, but the mechanisms remain unclear. Takeda G-protein coupled receptor 5 (TGR5) is a major receptor for secondary bile acids. We hypothesized that loss of TGR5 function remodels gut microbiota and influences blood pressure. Using CRISPR/Cas9, TGR5 knockout (Tgr5KO) rats on the Dahl Salt-Sensitive (S) background were generated and characterized. Compared to the control S rats, Tgr5KO rats demonstrated significantly lower blood pressure, a distinct shift in gut microbiota composition, and an increase in the secondary bile acid, particularly, glycodeoxycholic acid. Supplementation of glycodeoxycholic acid to the control S rats produced a similar gut microbial shift and lowered blood pressure. Furthermore, cecal microbiota transplantation from Tgr5KO to control S rats lowered blood pressure in the recipient rats. This first loss-of-function study demonstrates that deletion of TGR5 remodels gut microbiota, increases glycodeoxycholic acid, and lowers blood pressure regardless of TGR5 signaling status, identifying a promising gut–liver axis target for lowering hypertension.
Abstract from DOAJ. Public domain (CC0 1.0).
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Aryal, S., Mell, B., Tummala, R., et al. (2026). Gut microbiome drives glycodeoxycholic acid-mediated attenuation of hypertension. Gut Microbes. https://doi.org/10.1080/19490976.2026.2691346