RT Journal Article
T1 Mycophenolate mediated remodeling of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rats
A1 Robles-Vera, Iñaki
A1 de la Visitación, Néstor
A1 Toral, Marta
A1 Sánchez, Manuel
A1 Gómez-Guzmán, Manuel
A1 Jiménez, Rosario
A1 Romero, Miguel
A1 Duarte, Juan
K1 Mycophenolate
K1 Gut dysbiosis
K1 Hypertension
K1 Oxidative stress
K1 Inflammation
K1 SHR
K1 Lymph nodes
K1 Cytokines
K1 Ácido micofenólico
K1 Disbiosis
K1 Hipertensión
K1 Estrés oxidativo
K1 Inflamación
K1 Ratas endogámicas SHR
K1 Ganglios linfáticos
K1 Citocinas
AB 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.
PB Elsevier Masson
SN 0753-3322
YR 2020
FD 2020-12-31
LK http://hdl.handle.net/10668/4216
UL http://hdl.handle.net/10668/4216
LA en
NO 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.
DS RISalud
RD Apr 7, 2025