Targeting the gut microbiota with dietary fibers: a novel approach to prevent the development cardiovascular complications linked to systemic lupus erythematosus in a preclinical study
Javier Moleón,
Cristina González-Correa,
Iñaki Robles-Vera,
Sofía Miñano,
Néstor de la Visitación,
Antonio Manuel Barranco,
Natividad Martín-Morales,
Francisco O’Valle,
Laura Mayo-Martínez,
Antonia García,
Marta Toral,
Rosario Jiménez,
Miguel Romero,
Juan Duarte
Affiliations
Javier Moleón
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
Cristina González-Correa
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
Iñaki Robles-Vera
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Sofía Miñano
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
Néstor de la Visitación
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Antonio Manuel Barranco
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
Natividad Martín-Morales
Department of Pathology, School of Medicine, Instituto de Biopatología y Medicina Regenerativa (IBIMER) University of Granada, Granada, Spain
Francisco O’Valle
Department of Pathology, School of Medicine, Instituto de Biopatología y Medicina Regenerativa (IBIMER) University of Granada, Granada, Spain
Laura Mayo-Martínez
Centre for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad San Pablo CEU, CEU Universities. Campus Monteprincipe, Boadilla del Monte, San Pablo, Spain
Antonia García
Centre for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad San Pablo CEU, CEU Universities. Campus Monteprincipe, Boadilla del Monte, San Pablo, Spain
Marta Toral
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
Rosario Jiménez
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
Miguel Romero
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
Juan Duarte
Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
ABSTRACTThis study is to investigate whether dietary fiber intake prevents vascular and renal damage in a genetic mouse model of systemic lupus erythematosus (SLE), and the contribution of gut microbiota in the protective effects. Female NZBWF1 (SLE) mice were treated with resistant-starch (RS) or inulin-type fructans (ITF). In addition, inoculation of fecal microbiota from these experimental groups to recipient normotensive female C57Bl/6J germ-free (GF) mice was performed. Both fiber treatments, especially RS, prevented the development of hypertension, renal injury, improved the aortic relaxation induced by acetylcholine, and the vascular oxidative stress. RS and ITF treatments increased the proportion of acetate- and butyrate-producing bacteria, respectively, improved colonic inflammation and integrity, endotoxemia, and decreased helper T (Th)17 proportion in mesenteric lymph nodes (MLNs), blood, and aorta in SLE mice. However, disease activity (splenomegaly and anti-ds-DNA) was unaffected by both fibers. T cell priming and Th17 differentiation in MLNs and increased Th17 infiltration was linked to aortic endothelial dysfunction and hypertension after inoculation of fecal microbiota from SLE mice to GF mice, without changes in proteinuria and autoimmunity. All these effects were lower in GF mice after fecal inoculation from fiber-treated SLE mice. In conclusion, these findings support that fiber consumption prevented the development of hypertension by rebalancing of dysfunctional gut-immune system-vascular wall axis in SLE.