Lactobacillus fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling Toral Jiménez, Marta Romero Pérez, Miguel Rodríguez Nogales, Alba Jiménez Moleón, Rosario Robles Vera, Iñaki Algieri, Francesca Chueca-Portuna, Natalia Sánchez, Manuel Visitación Pastor, Néstor de la Olivares, Mónica García, Federico Pérez-Vizcaíno, Francisco Gálvez Peralta, Julio Juan Duarte Pérez, Juan Manuel T cells Endothelial dysfunction Gut dysbiosis The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice. Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium-dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)-driven superoxide production and Rho-kinase-mediated eNOS inhibition. LC40 treatment prevents all the aortic changes induced by tacrolimus. LC40 restores the imbalance between T-helper 17 (Th17)/regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and the spleen. Tacrolimus-induced gut dysbiosis, that is, it decreases microbial diversity, increases the Firmicutes/Bacteroidetes (F/B) ratio and decreases acetate- and butyrate-producing bacteria, and these effects are prevented by LC40. Fecal microbiota transplantation (FMT) from LC40-treated mice to control mice prevents the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus. LC40 treatment prevents hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects are associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes. 2024-01-29T10:53:25Z 2024-01-29T10:53:25Z 2018-05-30 journal article Toral M, Romero M, Rodríguez-Nogales A, Jiménez R, Robles-Vera I, Algieri F, Chueca-Porcuna N, Sánchez M, de la Visitación N, Olivares M, García F, Pérez-Vizcaíno F, Gálvez J, Duarte J. Lactobacillus fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling. Mol Nutr Food Res. 2018 Jul;62(14):e1800033. doi: 10.1002/mnfr.201800033. Epub 2018 Jun 28. PMID: 29851248. PMID: 29851248 https://hdl.handle.net/10481/87474 10.1002/mnfr.201800033 eng http://creativecommons.org/licenses/by/4.0/ embargoed access Atribución 4.0 Internacional WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim