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Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats

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Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain
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Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA, 18001 Granada, Spain
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Ciber de Enfermedades Cardiovasculares (CIBERCV), 18011 Granada, Spain
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Microbiome Consortium and Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43537, USA
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Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USA
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Gene Regulation in Cardiovascular Remodeling and Inflammation Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28001 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Antioxidants 2020, 9(12), 1199; https://doi.org/10.3390/antiox9121199
Received: 3 November 2020 / Revised: 26 November 2020 / Accepted: 27 November 2020 / Published: 28 November 2020
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
Microbiota is involved in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzed whether MMF improves dysbiosis in mineralocorticoid-induced hypertension. Male Wistar rats were assigned to three groups: untreated (CTR), deoxycorticosterone acetate (DOCA)-salt, and DOCA treated with MMF for 4 weeks. MMF treatment reduced systolic BP, improved endothelial dysfunction, and reduced oxidative stress and inflammation in aorta. A clear separation in the gut bacterial community between CTR and DOCA groups was found, whereas the cluster belonging to DOCA-MMF group was found to be intermixed. No changes were found at the phylum level among all experimental groups. MMF restored the elevation in lactate-producing bacteria found in DOCA-salt joined to an increase in the acetate-producing bacteria. MMF restored the percentage of anaerobic bacteria in the DOCA-salt group to values similar to control rats. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. This study demonstrates for the first time that MMF reduces gut dysbiosis in DOCA-salt hypertension models. This effect seems to be related to its capacity to improve gut integrity due to reduced sympathetic drive in the gut associated with reduced brain neuroinflammation. View Full-Text
Keywords: mycophenolate; gut dysbiosis; hypertension; oxidative stress; inflammation; (deoxycorticosterone acetate) DOCA-salt model mycophenolate; gut dysbiosis; hypertension; oxidative stress; inflammation; (deoxycorticosterone acetate) DOCA-salt model
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MDPI and ACS Style

Robles-Vera, I.; de la Visitación, N.; Sánchez, M.; Gómez-Guzmán, M.; Jiménez, R.; Moleón, J.; González-Correa, C.; Romero, M.; Yang, T.; Raizada, M.K.; Toral, M.; Duarte, J. Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats. Antioxidants 2020, 9, 1199. https://doi.org/10.3390/antiox9121199

AMA Style

Robles-Vera I, de la Visitación N, Sánchez M, Gómez-Guzmán M, Jiménez R, Moleón J, González-Correa C, Romero M, Yang T, Raizada MK, Toral M, Duarte J. Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats. Antioxidants. 2020; 9(12):1199. https://doi.org/10.3390/antiox9121199

Chicago/Turabian Style

Robles-Vera, Iñaki, Néstor de la Visitación, Manuel Sánchez, Manuel Gómez-Guzmán, Rosario Jiménez, Javier Moleón, Cristina González-Correa, Miguel Romero, Tao Yang, Mohan K. Raizada, Marta Toral, and Juan Duarte. 2020. "Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats" Antioxidants 9, no. 12: 1199. https://doi.org/10.3390/antiox9121199

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