Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.

Autor:	Yan X; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Jin J; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Su X; Division of Endocrinology and Metabolism (X.S., Z.W.), Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.; Division of Geriatrics (X.S., Z.W.), Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China., Yin X; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Gao J; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Wang X; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Zhang S; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Bu P; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Wang M; Medical Data Research Center, Providence Health & Services, Portland, OR (M.W.)., Zhang Y; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.)., Wang Z; Division of Endocrinology and Metabolism (X.S., Z.W.), Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.; Division of Geriatrics (X.S., Z.W.), Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China., Zhang Q; From the Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan (X. Yan, J.J., X. Yin, J.G., X.W., S.Z., P.B., Y.Z., Q.Z.).
Jazyk:	angličtina
Zdroj:	Circulation research [Circ Res] 2020 Mar 27; Vol. 126 (7), pp. 839-853. Date of Electronic Publication: 2020 Feb 13.
DOI:	10.1161/CIRCRESAHA.119.316394
Abstrakt:	Rationale: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. Objective: To reveal the roles and mechanisms of intestinal flora in hSIH development. Methods and Results: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid. Conclusions: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.
Databáze:	MEDLINE
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