Salt-dependent Role of Human Gut Commensal Coprococcus comes in Blood Pressure and Inflammation

Abstract

Introduction: We previously identified the effect of Coprococcus come, a common human gut microflora, on blood pressure regulation due to its metabolism of angiotensin-converting enzyme inhibitors (ACEi). Despite being reported as a butyrate-producer, there are no studies on C. comes in its direct role in hypertension and inflammation. Importantly, C. comes was enriched in the African American hypertensive population, almost three-fourths of whom were found salt sensitive. Therefore, we hypothesized that C. comes increased blood pressure and associated systemic inflammation in a salt-dependent manner. Methods: Once per day for 13 consecutive days, male Dahl salt-sensitive (S) rats (N=7-8/group) were administered 109 CFU of C. comes via oral gavage on both low and high salt diet. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure were recorded on day 13 by radio-telemetry. On day 14, spleen (the key organ in systemic inflammation) and kidney (the key organ in salt hypertension) were collected for analyses of inflammatory markers by real time PCR and flow cytometry. Results: In low salt rats, the administration of C. comes did not significantly change blood pressures, but resulted in immunosuppression in the spleen, as evidenced by decreased inflammatory markers Il6 (0.79 fold, p<0.05) and Il17rc (0.74 fold, p<0.001). In contrast, there were significant increases in the S rats on high salt+ C. comes vs high salt in systolic blood pressure (183.2 vs 179.9 mmHg, p<0.01), diastolic blood pressure (130.5 vs 127.1 mmHg, p<0.01), and mean arterial pressures (156.7 vs 151.8 mmHg, p<0.0001) during nighttime, but not daytime. The administration of C. comes in high salt rats led to increased inflammation in the spleen, as measured by the percentage of CD11b/c+ cells (high salt+ C. comes 2.9% vs high salt 2.1% p<0.05) and CD68+ cells (high salt+ C. comes 0.28% vs high salt 0.22% p<0.05), as well as in the kidney, as measured by inflammatory markers Il1b (4.4 fold, p<0.05), Il17rc (8.8 fold, p<0.05), and Tnf (1.67 fold, p<0.05). Conclusion: C. comes, an ACEi degrader, suppressed splenic inflammation in the male S rats on a low salt diet without impacting blood pressure. However, on high salt diet, C. comes administration resulted in increased splenic and renal inflammation as well as increased blood pressure in the male S rats. These findings support the pathogenic role of C. comes in salt-induced hypertension, providing evidence for targeting C. comes in blood pressure control. This study is funded by NIH R21AG079357 and AHA CDA 852969. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.