Publication: Mycophenolate mediated remodeling of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rats
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Date
2020-12-31
Authors
Robles-Vera, Iñaki
de la Visitación, Néstor
Toral, Marta
Sánchez, Manuel
Gómez-Guzmán, Manuel
Jiménez, Rosario
Romero, Miguel
Duarte, Juan
Advisors
Journal Title
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Volume Title
Publisher
Elsevier Masson
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Abstract
Microbiota has a role in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzes whether MMF improves dysbiosis in a genetic model of hypertension. Twenty weeks old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were randomly divided into three groups: untreated WKY, untreated SHR, and SHR treated with MMF for 5 weeks. MMF treatment restored gut bacteria from the phyla Firmicutes and Bacteroidetes, and acetate- and lactate-producing bacteria to levels similar to those found in WKY, increasing butyrate-producing bacteria. MMF increased the percentage of anaerobic bacteria in the gut. 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. MMF increased the lower regulatory T cells proportion in mesenteric lymph nodes and Th17 and Th1 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that MMF reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity due to reduced sympathetic drive in the gut associated to the reduced brain neuroinflammation.
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MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Cardiovascular Agents::Antihypertensive Agents
Medical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Arteries::Aorta::Aorta, Thoracic
Medical Subject Headings::Organisms::Bacteria
Medical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Hemodynamics::Blood Pressure
Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestine, Large::Colon
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines
Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Dysbiosis
Medical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Hypertension
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation Mediators
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Caproates::Mycophenolic Acid
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Electrophysiological Phenomena::Electrophysiological Processes::Neuroimmunomodulation
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus::Hypothalamus, Anterior::Paraventricular Hypothalamic Nucleus
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Rats, Inbred Strains::Rats, Inbred SHR
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Rats, Inbred Strains::Rats, Inbred WKY
Medical Subject Headings::Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Sympathetic Nervous System
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Bacteria::Bacteria, Anaerobic
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological::Models, Genetic
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes, Regulatory
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Volatile::Butyrates
Medical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Microbiota
Medical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Arteries::Aorta
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Organisms::Bacteria::Bacteroidetes
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus
Medical Subject Headings::Anatomy::Tissues::Lymphoid Tissue::Lymph Nodes
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Volatile::Acetates
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactates
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Cardiovascular Agents::Antihypertensive Agents
Medical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Arteries::Aorta::Aorta, Thoracic
Medical Subject Headings::Organisms::Bacteria
Medical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Hemodynamics::Blood Pressure
Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestine, Large::Colon
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines
Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Dysbiosis
Medical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Hypertension
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation Mediators
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Caproates::Mycophenolic Acid
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Electrophysiological Phenomena::Electrophysiological Processes::Neuroimmunomodulation
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus::Hypothalamus, Anterior::Paraventricular Hypothalamic Nucleus
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Rats, Inbred Strains::Rats, Inbred SHR
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Rats, Inbred Strains::Rats, Inbred WKY
Medical Subject Headings::Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Sympathetic Nervous System
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Bacteria::Bacteria, Anaerobic
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological::Models, Genetic
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes, Regulatory
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Volatile::Butyrates
Medical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Microbiota
Medical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Arteries::Aorta
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Organisms::Bacteria::Bacteroidetes
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus
Medical Subject Headings::Anatomy::Tissues::Lymphoid Tissue::Lymph Nodes
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Volatile::Acetates
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactates
DeCS Terms
CIE Terms
Keywords
Mycophenolate, Gut dysbiosis, Hypertension, Oxidative stress, Inflammation, SHR, Lymph nodes, Cytokines, Ácido micofenólico, Disbiosis, Hipertensión, Estrés oxidativo, Inflamación, Ratas endogámicas SHR, Ganglios linfáticos, Citocinas
Citation
Robles-Vera I, de la Visitación N, Toral M, Sánchez M, Gómez-Guzmán M, Jiménez R, et al. Mycophenolate mediated remodeling of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rats. Biomed Pharmacother. 2021 Mar;135:111189.