Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats
| Autor: | Mohan K. Raizada, Juan Duarte, Manuel Sánchez, Manuel Gómez-Guzmán, Marta Toral, Cristina González-Correa, Tao Yang, Javier Moleón, Iñaki Robles-Vera, Rosario Jiménez, Néstor de la Visitación, Miguel Romero |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Junta de Andalucía, European Union, Instituto de Salud Carlos III - ISCIII, National Heart, Lung, and Blood Institute (United States), European Regional Development Fund (ERDF/FEDER), [Robles-Vera,I, de la Visitación,N, Sánchez,M, Gómez-Guzmán,M, Jiménez,R, Moleón,J, González-Correa,C, Romero,M, Duarte,J] Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain. [Sánchez,M, Gómez-Guzmán,M, Jiménez,R, Duarte,J] Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA,Granada, Spain. [Jiménez,R, Toral,M, Duarte,J] Ciber de Enfermedades Cardiovasculares (CIBERCV), Granada, Spain. [Yang,T] 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, USA. [Raizada,MK] Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA. [Toral,M] Gene Regulation in Cardiovascular Remodeling and Inflammation Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., This work was supported by Grants from Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (SAF2017-84894-R), Junta de Andalucía (CTS-164), with funds from the European Union, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV), Spain, and National Heart, Lung and Blood Institute (NHLBI) grant HL102033. M.T. is a postdoctoral fellow of Instituto de Salud Carlos III (Sara Borrell Program). I.R.V. is a predoctoral fellow of MINECO. The cost of this publication was paid in part with funds from the European Union (Fondo Europeo de Desarrollo Regional, FEDER, 'FEDER una manera de hacer Europa')., Regional Government of Andalusia (España), Unión Europea, Instituto de Salud Carlos III, NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry mycophenolate gut dysbiosis hypertension oxidative stress inflammation (deoxycorticosterone acetate) DOCA-salt model (Deoxycorticosterone acetate) DOCA-salt model 030204 cardiovascular system & hematology Gut flora medicine.disease_cause Biochemistry Anatomy::Cardiovascular System::Blood Vessels::Arteries::Aorta [Medical Subject Headings] Gut dysbiosis 0302 clinical medicine Organisms::Eukaryota::Animals [Medical Subject Headings] oxidative stress Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats Wistar [Medical Subject Headings] Endothelial dysfunction mycophenolate biology Microbiota Estrés oxidativo Organisms::Bacteria::Bacteria Anaerobic [Medical Subject Headings] Phenomena and Processes::Microbiological Phenomena::Microbiota [Medical Subject Headings] Hypertension Diseases::Pathological Conditions Signs and Symptoms::Pathologic Processes::Dysbiosis [Medical Subject Headings] Anaerobic bacteria medicine.symptom hormones hormone substitutes and hormone antagonists medicine.medical_specialty hypertension Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids Acyclic::Acetates [Medical Subject Headings] Check Tags::Male [Medical Subject Headings] Inflammation Acetato de desoxicorticosterona Article Diseases::Cardiovascular Diseases::Vascular Diseases::Hypertension [Medical Subject Headings] Phenomena and Processes::Physiological Phenomena::Physiological Processes::Stress Physiological::Oxidative Stress [Medical Subject Headings] 03 medical and health sciences gut dysbiosis Internal medicine Hipertensión Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Hemodynamics::Blood Pressure [Medical Subject Headings] medicine Mycophenolate Molecular Biology Neuroinflammation Inflamación Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Mineralocorticoids [Medical Subject Headings] business.industry lcsh:RM1-950 (deoxycorticosterone acetate) DOCA-salt model Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings] Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactates::Lactic Acid [Medical Subject Headings] Cell Biology Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus [Medical Subject Headings] medicine.disease biology.organism_classification lcsh:Therapeutics. Pharmacology 030104 developmental biology Endocrinology Blood pressure inflammation Oxidative stress business Dysbiosis |
| Zdroj: | Digibug: Repositorio Institucional de la Universidad de Granada Universidad de Granada (UGR) Antioxidants Volume 9 Issue 12 Digibug. Repositorio Institucional de la Universidad de Granada instname Repisalud Instituto de Salud Carlos III (ISCIII) Antioxidants, Vol 9, Iss 1199, p 1199 (2020) |
| DOI: | 10.3390/antiox9121199 |
| Popis: | 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. MaleWistar 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 andDOCAgroups was found, whereas the cluster belonging toDOCA-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 e ect seems to be related to its capacity to improve gut integrity due to reduced sympathetic drive in the gut associated with reduced brain neuroinflammation. Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad SAF2017-84894-R Junta de Andalucía CTS-164 European Union (EU) Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (CIBER-CV), Spain United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) HL102033 European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa") |
| Databáze: | OpenAIRE |
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