Sex-dependent modulation of T and NK cells and gut microbiome by low sodium diet in patients with primary aldosteronism

Front Immunol. 2024 Dec 19:15:1428054. doi: 10.3389/fimmu.2024.1428054. eCollection 2024.

Abstract

Background: High dietary sodium intake is a major cardiovascular risk factor and adversely affects blood pressure control. Patients with primary aldosteronism (PA) are at increased cardiovascular risk, even after medical treatment, and high dietary sodium intake is common in these patients. Here, we analyze the impact of a moderate dietary sodium restriction on microbiome composition and immunophenotype in patients with PA.

Methods: Prospective two-stage clinical trial including two subgroups: 15 treatment-naive PA patients compared to matched normotensive controls; and 31 PA patients on mineralocorticoid receptor antagonist treatment before and three months after sodium restriction. Patients underwent blood pressure measurements, laboratory tests, analysis of peripheral blood mononuclear cells via flow cytometry and microbiome analysis.

Results: We observed a higher percentage of Tregs in treatment-naive PA patients (p = 0.0303), while the abundance of Bacteroides uniformis was higher in PA patients compared to normotensive controls (p = 0.00027) and the abundance of Lactobacillus species however was higher in the subgroup of normotensive controls (p = 0.0290). Sodium restriction was accompanied by a decrease in pro-inflammatory Tc17 cells in male patients (p = 0.0081, females p = 0.3274). Bacteroides uniformis abundance was higher in female patients (0.01230, p = 0.0016) and decreased upon sodium restriction (0.002309, p = 0.0068).

Conclusion: Dietary sodium restriction in patients with PA modulates the peripheral immune cell composition toward a less inflammatory phenotype. This suggests a potential mechanism by which sodium reduction modulates immune cell composition, leading to blood pressure reduction and positively impacting cardiovascular risk.

Keywords: Tc17; Tregs (regulatory T cells); microbiome; primary aldosteronism (PA); sodium.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Diet, Sodium-Restricted*
  • Female
  • Gastrointestinal Microbiome* / immunology
  • Humans
  • Hyperaldosteronism* / immunology
  • Killer Cells, Natural* / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • Sex Factors
  • T-Lymphocytes / immunology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Deutsche Forschungsgemeinschaft (Heisenberg Professorship 325768017 to NR and Projektnummer: 314061271-TRR205 to CA, HS, MR, and NR, Emmy Noether Grant 426120468 to MS, Clinician Scientist PRogram In Vascular MEdicine (PRIME, MA 2186/14-1 to HS)), Else Kröner-Fresenius Stiftung in support of the German Conn’s Registry-Else-Kröner Hyperaldosteronism Registry (2013_A182, 2015_A171 and 2019_A104 to MR), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 694913 to MR), Eva Luise und Horst Köhler Stiftung & Else Kröner-Fresenius-Stiftung (2019_KollegSE.03 to HN) and by the Förderprogramm für Forschung und Lehre (FöFoLe) Reg.-Nr. 37/2019 to TM, Reg.-Nr. 1051 to CA, Reg.-Nr. 1138 to AG and Reg.-Nr. 1169 to HN). Further funding was provided by the Bavarian Cancer Research Center (BZKF) (AG and TANGO to SKo (Sebastian Kobold)), the Deutsche Forschungsgemeinschaft (DFG, grant number GO 3823/1-1 to AG; grant number KO5055-2-1, KO5055/3-1 and 510821390 to SKo), by the SFB-TRR 338/1 2021–452881907 (to SKo), the international doctoral program ‘i-Target: immunotargeting of cancer’ (funded by the Elite Network of Bavaria; to SKo), the Melanoma Research Alliance (grant number 409510 to SKo), Marie Sklodowska-Curie Training Network for the Immunotherapy of Cancer (IMMUTRAIN; funded by the Horizon 2020 programme of the European Union, to SKo), Marie Sklodowska-Curie Training Network for Optimizing Adoptive T Cell Therapy of Cancer (funded by the Horizon 2020 programme of the European Union; grant 955575 to SKo), Else Kroüner-Fresenius-Stiftung (to AG and IOLIN to SKo), German Cancer Aid (AvantCAR.de to SKo), the Wilhelm-Sander-Stiftung (to SKo), Ernst Jung Stiftung (to SKo), Institutional Strategy LMUexcellent of LMU Munich (within the framework of the German Excellence Initiative, to SKo), the Go-Bio-Initiative (to SKo), the m4-Award of the Bavarian Ministry for Economical Affairs (to SKo), Bundesministerium für Bildung und Forschung (to SKo), European Research Council (Starting Grant 756017 and PoC Grant 101100460 to SKo), Fritz-Bender Foundation (to SKo), Deutsche Joseí Carreras Leukämie Stiftung (to SKo), Hector Foundation (to SKo), Bavarian Research Foundation (BAYCELLATOR to SKo), and the Bruno and Helene Jöster Foundation (360°CAR to SKo).