Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity
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Authorde 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
HypertensionEndothelial DysfunctionGut dysbiosisImmune systemSystemic lupus erythematosusTLR7 activation
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
SponsorshipComisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (MINECO) (SAF2017-84894-R, PID2020-116347RBI00); Junta de Andalucía (CTS 164, P20_00193) with funds from the European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV); Instituto de Salud Carlos III (Sara Borrell Program); MINECO; European Union (Fondo Europeo de Desarrollo Regional, FEDER)
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.