Suchergebnisse

Previous experiments in animals and humans show that shifts in microbiota and its metabolites are linked to hypertension. The present study investigates whether doxycycline (DOX, a broad-spectrum tetracycline antibiotic) improves dysbiosis, prevent cardiovascular pathology and attenuate hypertension in deoxycorticosterone acetate (DOCA)-salt rats, a renin-independent model of hypertension. Male Wistar rats were randomly assigned to three groups: control, DOCA-salt hypertensive rats, DOCA-salt treated with DOX for 4 weeks. DOX decreased systolic blood pressure, improving endothelial dysfunction and reducing aortic oxidative stress and inflammation. DOX decreased lactate-producing bacterial population and plasma lactate levels, improved gut barrier integrity, normalized endotoxemia, plasma noradrenaline levels and restored the Treg content in aorta. These data demonstrate that DOX through direct effects on gut microbiota and its non-microbial effects (anti-inflammatory and immunomodulatory) reduces endothelial dysfunction and the increase in blood pressure in this low-renin form of hypertension. ; Grants from Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (SAF2017-84894-R) ; Ministerio de Ciencia e Innovación (PID2020-116347RB-I00) ; Junta de Andalucía (CTS-164, P20_00193) ; European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV; Ciberes) ; Instituto de Salud Carlos III (Sara Borrell Program) ; European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa")

This work was supported by Grants from Comision Interministerial de Ciencia y Tecnologia, Ministerio de Economia y competitividad (SAF2017-84894-R), Junta de Andalucia (CTS-164) with funds from the European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV; Ciberes), Spain. M.T. is a postdoctoral fellow of Instituto de Salud Carlos III (Sara Borrell Program). I.R.-V., and JM-M are predoctoral fellow of MINECO. The cost of this publication was paid in part with funds from the European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa"). ; Our group tested the effects of Lactobacillus fermentum CECT5716 (LC40) and/or Bifidobacterium breve CECT7263 (BFM) in the prevention of gut dysbiosis, hypertension and endothelial dysfunction in a pharmacologically-induced model of systemic lupus erythematosus (SLE). We treated eight-week-old BALB/cByJRj mice without (Ctrl) or with the agonist of TLR-7 Imiquimod (IMQ) for 8 weeks. Concomitantly, LC40 (109 CFU/mL) and BFM (109 CFU/mL) were administered through oral gavage once a day. IMQ induced intestinal dysbiosis consisting of a decrease in the -diversity measured with Chao-richness and numbers of species. LC40 and BFM did not restore these parameters. The three-dimensional principal component analysis of bacterial taxa in stool samples presented perfect clustering between Ctrl and IMQ groups. Clusters corresponding to LC40 and BFM were more akin to IMQ. BFM and LC40 were detected colonizing the gut microbiota of mice treated respectively. LC40 and BFM decreased plasma double-stranded DNA autoantibodies, and B cells in spleen, which were increased in the IMQ group. Also, LC40 and BFM treatments activated TLR9, reduced T cells activation, and Th17 polarization in mesenteric lymph nodes. Aortae from IMQ mice displayed a decreased endothelium-dependent vasodilator response to acetylcholine linked to pro-inflammatory and pro-oxidative status, which were normalized by both BFM and LC40. In conclusion, we demonstrate for the first time that the chronic treatment with LC40 or BFM prevented hypertension and endothelial dysfunction in a mouse lupus model induced by TLR-7 activation. ; Comision Interministerial de Ciencia y Tecnologia, Ministerio de Economia y competitividad SAF2017-84894-R ; Junta de Andalucia CTS-164 ; European Commission ; Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV; Ciberes), Spain ; European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa")

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. ; Comisión 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)

This research was funded by the FEDER-INNTERCONECTA-CDTI program (CDTI, Centre for the Development of Industrial Technology; NATURPICK Project ITC-20181038), by the Junta de Andalucia (CTS 164) and by Instituto de Salud Carlos III (PI19/01058) with funds from the European Union. T.V. is a postdoctoral fellow from Instituto de Investigacion Biosanitaria de Granada; A.J.R.-M. and L.H.-G. are predoctoral fellows from University of Granada ("Programa de Doctorado: Medicina Clinica y Salud Publica"); P.D.-E. is a postdoctoral fellow from University of Granada. The CIBER-EHD and CIBERCV are funded by the Instituto de Salud Carlos III. ; Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesityassociated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ß, Il-6, Tnf-a, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-a, Ppar-g, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome. ; FEDER-INNTERCONECTA-CDTI program (CDTI, Centre for the Development of Industrial Technology) ITC-20181038 ; Junta de Andalucia CTS 164 ; Instituto de Salud Carlos III European Commission PI19/01058 European Commission Instituto de Salud Carlos III ; European Commission