Hanna F. Nowotny ¹ Tingting Zheng ² Thomas Marchant Seiter ¹ Jing Ju ¹ Holger Schneider ¹ Matthias Kroiss ¹ Anna Lina Sarkis ¹ Lisa Sturm ¹ Vera Britz ¹ Andreas Lechner ^1,3 Anne L. Potzel ^3,4,5 Sonja Kunz ¹ Martin Bidlingmaier ¹ Klaus Neuhaus ⁶ Adrian Gottschlich ^7,8,9 Sebastian Kobold ^10,11,7 Nicole Reisch ¹ Melanie Schirmer ² Martin Reincke ¹ Christian Adolf ^1*

• ¹ Medical Clinic and Polyclinic IV, LMU Munich University Hospital, Munich, Germany
• ² Technical University of Munich, Munich, Germany
• ³ German Center for Diabetes Research (DZD), Neuherberg, Germany
• ⁴ Physicians Association for Nutrition, Munich, Germany
• ⁵ Helmholtz Center München, Helmholtz Association of German Research Centres (HZ), Neuherberg, Germany
• ⁶ Core Facility Microbiome Unit NGS, Institute for Food and Health, Technical University of Munich, Freising, Bavaria, Germany
• ⁷ Division of Clinical Pharmacology, LMU Munich University Hospital, Munich, Germany
• ⁸ Bavarian Cancer Research Center (BZKF), Munich, Germany
• ⁹ Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
• ¹⁰ German Cancer Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany
• ¹¹ Clinical Pharmacology Unit, Helmholtz Center Munich, Helmholtz Association of German Research Centers (HZ), Neuherberg, Germany

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.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 proinflammatory 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).Dietary sodium restriction in patients with PA modulates the peripheral immune cell composition towards 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.