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Publications

Journal Article Ppublish

PubMed: 41254951 DOI: 10.1080/19490976.2025.2586324

The probiotic Limosilactobacillus fermentum CECT5716 enhances the antihypertensive response to hydrochlorothiazide in spontaneously hypertensive rats.

Gut Microbes 17(1):2586324

Authors: Cristina González-Correa, Sofia Miñano, Javier Moleón, Marta Toral, Iñaki Robles-Vera, Manuel Sánchez, Rosario Jiménez, Monica Olivares, Natividad Martín-Morales, Francisco O'Valle, Eduardo Guerra-Hernández, Miguel Romero, Manuel Gómez-Guzmán, Juan Duarte

Affiliations

  • Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
  • Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA, Granada, Spain.
  • Department of Translational Rheumatology and Immunology, Institute of Musculoskeletal Medicine, University of Münster, Münster, Germany.
  • Ciber de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
  • Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain. Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA, Granada, Spain.
  • Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain. Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA, Granada, Spain. Ciber de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
  • Biosearch S.A.U. (a Kerry® Company), R&D Department, Granada, Spain.
  • Instituto de Biopatología y Medicina Regenerativa (IBIMER), Department of Pathology, School of Medicine, University of Granada, Granada, Spain.
  • Department of Nutrition and Bromatology, University of Granada, Granada, Spain.

Abstract

Limosilactobacillus fermentum CECT5716 (LC40) consumption reduces hypertension and improves endothelial dysfunction in spontaneously hypertensive rats (SHRs). The diuretic hydrochlorothiazide (HCTZ) lowers blood pressure in SHR but disrupts the gut microbiota balance. In this study, we investigated whether the LC40 could enhance the antihypertensive effects of HCTZ. Interestingly, we found that coadministration of LC40 with HCTZ potentiated the beneficial effects of HCTZ on endothelial dysfunction and blood pressure without altering plasma HCTZ concentrations or exacerbating electrolyte imbalances. These protective effects were associated with normalization of microbiota alterations, including a reduction in the Firmicutes/Bacteroidota ratio, suppression of lipopolysaccharide biosynthesis, and an increase in acetate-producing bacteria. Additionally, LC40 reduced intestinal pathology and endotoxemia. Furthermore, the HCTZ + LC40-treated rats exhibited reduced neuroinflammation and sympathetic activity, along with an immunoregulatory effect characterized by increased regulatory T cell infiltration and a reduction of vascular oxidative stress in the aorta. The beneficial effects of LC40 in HCTZ-treated rats appeared to be microbiota dependent, as they were replicated through fecal microbiota transplantation in germ-depleted normotensive rats. Our findings identify the gut microbiota as a novel therapeutic target to enhance the antihypertensive effects of diuretics. The coadministration of LC40 with HCTZ modulates immune responses, providing a promising strategy to improve hypertension management.

MeSH

Hypertension, Blood, Fecal Microbiota Transplantation, Hydrochlorothiazide, Blood Pressure, Antihypertensive Agents, Probiotics, Immune System, Diuretics, Gastrointestinal Microbiome, Microbiota