Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats
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AuthorRobles Vera, Iñaki; de la Visitación, Néstor; Sánchez, Manuel; Gómez Guzmán, Manuel; Jiménez Moleón, Rosario; Moleón Moya, Javier; González Correa, Cristina; Romero Pérez, Miguel; Duarte Pérez, Juan Manuel
MycophenolateGut dysbiosisHypertensionOxidative stressInflammation(Deoxycorticosterone acetate) DOCA-salt model
García-García, G., Fernández-Álvarez, F., Cabeza, L., Delgado, Á. V., Melguizo, C., Prados, J. C., & Arias, J. L. (2020). Gemcitabine-Loaded Magnetically Responsive Poly (ε-caprolactone) Nanoparticles against Breast Cancer. Polymers, 12(12), 2790. [doi:10.3390/antiox9121199]
SponsorshipComisión 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")
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.