Mycophenolate mediated remodeling of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rats
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AuthorRobles Vera, Iñaki; de la Visitación, Néstor; Sánchez, Manuel; Gómez Guzmán, Manuel; Jiménez Moleón, Rosario; Romero, Miguel; Duarte Pérez, Juan Manuel
MycophenolateGut dysbiosisHypertensionOxidative stressInflammationSHR
Iñaki Robles-Vera, Néstor de la Visitación, Marta Toral, Manuel Sánchez, Manuel Gómez-Guzmán, Rosario Jiménez, Miguel Romero, Juan Duarte, Mycophenolate mediated remodeling of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rats, Biomedicine & Pharmacotherapy, Volume 135, 2021, 111189, ISSN 0753-3322, [https://doi.org/10.1016/j.biopha.2020.111189]
SponsorshipComision Interministerial de Ciencia y Tecnologia, Ministerio de Economia y competitividad SAF201784894R; Junta de Andalucia CTS-164; European Commission; Spanish Government; Instituto de Salud Carlos III (CIBERCV) , Spain; European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa")
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.