Abstract P171: Gut Microbiota-Derived Hydrogen Sulfide is Reduced in Spontaneously Hypertensive Rats

Abstract

Introduction: Gut bacteria play a significant role in host homeostasis, and gut dysbiosis has been associated with many conditions including hypertension (HTN). Endogenous hydrogen sulfide (H 2 S) is an important freely-diffusing molecule that can modulate neural, cardiovascular and immune system activity, and circulating levels of H 2 S are reduced in animals and humans with HTN. While most research on the role of H 2 S in HTN has focused on H 2 S produced by host tissues, H 2 S produced by gut bacteria may also enter the host circulation. We investigated whether the spontaneously hypertensive rat (SHR), an established model of HTN, has a disruption in gut bacteria-derived H 2 S production. Methods: Bacterial DNA from fecal samples of adult male normotensive Wistar-Kyoto (WKY) and SHR was isolated for 16s bacterial genomic sequencing. WKY and SHR fecal and plasma samples were analyzed for H 2 S levels using modified methylene blue assay. Blood pressures were determined in all rats at several time points using a tail cuff. Data are expressed as mean±SEM, with P<0.05 considered statistically significant. Results: We found a significant reduction in the abundance of two H 2 S-producing gut bacteria in the SHR compared to WKY: Enterobacteriaceae (1.423e-005±1.056e-005 vs. 0.0002329±7.853e-005, n=6, P<0.05), and Clostridiaceae (0.01134±0.00431 vs. 0.06408±0.01416, n=6, P<0.01). This decrease in the H 2 S-producing gut bacteria was also associated with a significant reduction in fecal H 2 S levels (SHR: 0±0.01703 AU vs. WKY: 0.094±0.03385 AU, n=5; P<0.05) and lower plasma H 2 S levels (SHR: 0.3265±0.07817 AU vs. WKY: 0.6850±0.1790 AU, n=2) in the SHR compared to the WKY. Conclusion: These results suggest that diminished gut bacterial production of H 2 S may contribute to the reduced H 2 S observed in host circulation in established HTN.