Abstract: TH-PO918
Effects of High Dietary Salt on Immunome and Microbiome Composition: Results from a Randomized Clinical Trial
Session Information
- Health Maintenance, Nutrition, Metabolism - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Bartolomaeus, Hendrik, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Anandakumar, Harithaa, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Chen, Chia-Yu, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Mähler, Anja, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Müller, Dominik N., Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, Buch, Berlin, Germany
- Forslund, Sofia Kirke, Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, Buch, Berlin, Germany
- Wilck, Nicola, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Background
Increased dietary salt intake ranks among the most prominent nutritional risk factors worldwide and has been tied to arterial hypertension and all-cause mortality. The mechanisms responsible are incompletely understood and have recently been extended to include inflammatory and microbiome-associated mechanisms. Building on our preliminary data, the present study investigates whether a moderate increase in salt intake in healthy subjects primes host physiology to a more transiently unstable state, potentially leading to changes in the microbiome-immune axis.
Methods
We conducted a prospective, randomized, double-blinded trial to evaluate the effect of high dietary salt in healthy participants (NCT03024567), where the intervention group (n = 19) was given 6g of salt (NaCl) in addition to their daily normal salt intake, essentially doubling the recommended salt intake against a placebo group (n=19) for 14 days. Clinical parameters, stool, and PBMC were collected at baseline and day 14. Shotgun metagenomic sequencing, metabolomics (stool and serum), and single-cell sequencing (Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITEseq)) of whole PBMC and CD4+ T cells (~150k single cells) was performed.
Results
Our results confirm previously established findings showing an increase in the dissimilarity of the microbiome composition (Jensen-Shannon Divergence) under a high salt diet. Differential abundance of the microbiome's functional space, as quantified by functional gut-specific modules, picked up a salt-specific module (M00494, NatK-NatR (sodium extrusion) two-component regulatory system) in the salt intervention group. A short-chain fatty acid-specific module (MF0128, Propionate conversion to succinate) was reduced in the salt arm. CITEseq revealed a significant amount of differently expressed genes (DEGs) solely in the salt group. We found 602 DEG in naïve conventional T cells (Tconv) and 202 DEGs in non-naïve Tconv, e.g. belonging to NF-kB and T cell receptor signaling pathways.
Conclusion
Our placebo-controlled study is the first to utilize different omics techniques to investigate and identify high-salt-induced changes in the microbiome and immunome in healthy individuals that may be relevant to the development of pathological conditions in the long term.