Robles-Vera, Iñakide la Visitación, NéstorToral, MartaSánchez, ManuelGómez-Guzmán, ManuelJiménez, RosarioRomero, MiguelDuarte, Juan2022-10-042022-10-042020-12-31Robles-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;135:111189.0753-3322http://hdl.handle.net/10668/4216Microbiota 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/MycophenolateGut dysbiosisHypertensionOxidative stressInflammationSHRLymph nodesCytokinesÁcido micofenólicoDisbiosisHipertensiónEstrés oxidativoInflamaciónRatas endogámicas SHRGanglios linfáticosCitocinasMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Cardiovascular Agents::Antihypertensive AgentsMedical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Arteries::Aorta::Aorta, ThoracicMedical Subject Headings::Organisms::BacteriaMedical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Hemodynamics::Blood PressureMedical Subject Headings::Anatomy::Cells::Cells, CulturedMedical Subject Headings::Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestine, Large::ColonMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::CytokinesMedical Subject Headings::Diseases::Animal Diseases::Disease Models, AnimalMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::DysbiosisMedical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::HypertensionMedical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation MediatorsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Caproates::Mycophenolic AcidMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Electrophysiological Phenomena::Electrophysiological Processes::NeuroimmunomodulationMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus::Hypothalamus, Anterior::Paraventricular Hypothalamic NucleusMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Rats, Inbred Strains::Rats, Inbred SHRMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Rats, Inbred Strains::Rats, Inbred WKYMedical Subject Headings::Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Sympathetic Nervous SystemMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-LymphocytesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Bacteria::Bacteria, AnaerobicMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological::Models, GeneticMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes, RegulatoryMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Volatile::ButyratesMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::MicrobiotaMedical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::Arteries::AortaMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Organisms::Bacteria::BacteroidetesMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HypothalamusMedical Subject Headings::Anatomy::Tissues::Lymphoid Tissue::Lymph NodesMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Volatile::AcetatesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactatesresearch article33388596Acceso abierto10.1016/j.biopha.2020.1111891950-6007