Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity de la Visitación, Néstor Robles Vera, Iñaki Moleón Moya, Javier González Correa, Cristina Aguilera Sánchez, Nazareth Gómez Guzmán, Manuel Sánchez Santos, Manuel Jiménez Moleón, Rosario Martín Morales, Natividad O'Valle Ravassa, Francisco Javier Romero Pérez, Miguel Duarte Pérez, Juan Manuel Hypertension Endothelial Dysfunction Gut dysbiosis Immune system Systemic lupus erythematosus TLR7 activation Our group has investigated the involvement of gut microbiota in hypertension in a murine model of systemic lupus erythematosus induced by Toll-like receptor (TLR)-7 activation. Female BALB/c mice were randomly assigned to four experimental groups: an untreated control (CTR), a group treated with the TLR7 agonist imiquimod (IMQ), IMQ-treated with vancomycin, and IMQtreated with a cocktail of broad-spectrum antibiotics. We carried out faecal microbiota transplant (FMT) from donor CTR or IMQ mice to recipient IMQ or CTR animals, respectively. Vancomycin inhibited the increase in blood pressure; improved kidney injury, endothelial function, and oxidative stress; and reduced T helper (Th)17 infiltration in aortas from IMQ-treated mice. The rise in blood pressure and vascular complications present in IMQ mice were also observed in the CTR mice recipients of IMQ microbiota. Reduced relative populations of Sutterella and Anaerovibrio were associated with high blood pressure in our animals, which were increased after stool transplantation of healthy microbiota to IMQ mice. The reduced endothelium-dependent vasodilator responses to acetylcholine induced by IMQ microbiota were normalized after interleukin-17 neutralization. In conclusion, gut microbiota plays a role in the TLR7-driven increase in Th17 cell, endothelial dysfunction, vascular inflammation, and hypertension. The vascular changes induced by IMQ microbiota were initiated by Th17 infiltrating the vasculature. 2021-09-21T07:31:20Z 2021-09-21T07:31:20Z 2021 info:eu-repo/semantics/article de la Visitación, N.; Robles-Vera, I.; Moleón, J.; González-Correa, C.; Aguilera-Sánchez, N.; Toral, M.; Gómez-Guzmán, M.; Sánchez, M.; Jiménez, R.; Martin-Morales, N.; et al. Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity. Antioxidants 2021, 10, 1426. https://doi.org/10.3390/ antiox10091426 http://hdl.handle.net/10481/70313 10.3390/ antiox10091426 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI