Salt-responsive gut commensal modulates TH17 axis and disease
Open accessAbstract
A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (T H 17) cells, which can also contribute to hypertension. Induction of T H 17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating T H 17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased T H 17 cells and increased blood pressure. Our results connect high salt intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.
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Diet has a critical role on gut microbiota function.
“This further illustrates the critical role diet has on gut microbiota function (Wilck et al., 2017)”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Wilck et al., 2017
Unhealthy dietary interventions, such as high-fat, high-sugar, and high-salt interventions, negatively impact the gut microbiome and induce intestinal inflammation by impairing TH17 cell functions.
“Unhealthy dietary interventions, such as high-fat, high-sugar, and high-salt interventions, have been shown to negatively impact the gut microbiome and induce intestinal inflammation by impairing TH17 cell functions.698–700”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [699]
The hypertensive effects of high-salt diets in experimental animals and humans are mediated by reduced levels of Lactobacillus and subsequent increases in proinflammatory T helper 17 cells.
“Recent data suggest that the hypertensive effects of high-salt diets in experimental animals and humans are mediated by reduced levels of Lactobacillus and subsequent increases in proinflammatory T helper 17 cells (54).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [54]
In mice, high salt intake altered the gut microbiota, and treatment with Lactobacillus murinus attenuated salt-induced increases in blood pressure by approximately 5 mmHg.
“In mice, high salt intake altered the GM, and treatment with Lactobacillus murinus attenuated salt-induced increases in BP by ~5 mmHg 104.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [104]
A pilot study in normotensive healthy humans reported that a high-salt diet for 14 days reduced intestinal survival of Lactobacillus and increased blood pressure, although a cause-and-effect relationship between altered gut microbiota and blood pressure was not established.
“A pilot study in normotensive, healthy humans reported that a high-salt diet for 14 days reduced intestinal survival of Lactobacillus and increased BP, although a cause-and-effect relationship between altered GM and BP was not established104.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [104]
Transferring dysbiotic faecal samples from patients with hypertension to germ-free mice or faeces from hypertensive stroke-prone SHRs to normotensive WKY rats increased blood pressure in the recipients.
“Further evidence for a causative role of gut dysbiosis in the genesis of hypertension came from faecal microbiota transplantation (FMT) experiments in which transferring dysbiotic faecal samples from patients with hypertension to germ-free mice90 or faeces from hypertensive stroke-prone SHRs to normotensive WKY rats92 increased blood pressure in the recipients.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [92]
Interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects in animal models and in patients with hypertension.
“Finally, studies in animal models and in patients with hypertension have reported that interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects87,92–99.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [92]
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Mancia, G., Kreutz, R., Brunström, M., Burnier, M., Grassi, G., Januszewicz, A., Muiesan, M. L., Tsioufis, K., Agabiti-Rosei, E., Algharably, E. A. E., et al. (2023) · Journal of Hypertension · doi:10.1097/hjh.0000000000003480 · Cited by 3,473 · see citing works
Microbial tryptophan catabolites in health and disease
Roager, H. M., & Licht, T. R. (2018) · Nature Communications · doi:10.1038/s41467-018-05470-4 · Cited by 2,236 · see citing works
Oparil, S., Acelajado, M. C., Bakris, G. L., Berlowitz, D. R., Cífková, R., Dominiczak, A. F., Grassi, G., Jordan, J., Poulter, N. R., Rodgers, A., et al. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.14 · Cited by 1,167 · see citing works
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
The gut microbiota at the intersection of diet and human health
Gentile, C. L., & Weir, T. L. (2018) · Science · doi:10.1126/science.aau5812 · Cited by 1,049 · see citing works
The Human Gut Microbiome: From Association to Modulation
Schmidt, T. S. B., Raes, J., & Bork, P. (2018) · Cell · doi:10.1016/j.cell.2018.02.044 · Cited by 845 · see citing works
Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors
Fiuza-Luces, C., Santos-Lozano, A., Joyner, M., Carrera-Bastos, P., Picazo, O., Zugaza, J. L., Izquierdo, M., Ruilope, L. M., & Lucia, A. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0065-1 · Cited by 803 · see citing works
Hezaveh, K., Shinde, R. S., Klötgen, A., Halaby, M. J., Lamorte, S., Ciudad, M. T., Quevedo, R., Neufeld, L., Liu, Z. Q., Jin, R., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.01.006 · Cited by 746 · see citing works
The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
Yang, T., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0018-2 · Cited by 753 · see citing works
Obesity, kidney dysfunction and hypertension: mechanistic links
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0145-4 · Cited by 654 · see citing works
Salt Reduction to Prevent Hypertension and Cardiovascular Disease
He, F. J., Tan, M., Ma, Y., & MacGregor, G. A. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.055 · Cited by 589 · see citing works
Host variables confound gut microbiota studies of human disease
Vujkovic-Cvijin, I., Sklar, J., Jiang, L., Natarajan, L., Knight, R., & Belkaid, Y. (2020) · Nature · doi:10.1038/s41586-020-2881-9 · Cited by 614 · see citing works
Bolte, L. A., Vich Vila, A., Imhann, F., Collij, V., Gacesa, R., Peters, V., Wijmenga, C., Kurilshikov, A., Campmans-Kuijpers, M. J. E., Fu, J., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-322670 · Cited by 595 · see citing works
You Are What You Eat—The Relationship between Diet, Microbiota, and Metabolic Disorders—A Review
Moszak, M., Szulińska, M., & Bogdański, P. (2020) · Nutrients · doi:10.3390/nu12041096 · Cited by 397 · see citing works
RETRACTED ARTICLE: Role of the gut microbiome in chronic diseases: a narrative review
Vijay, A., & Valdes, A. M. (2022) · European Journal of Clinical Nutrition · doi:10.1038/s41430-021-00991-6 · Cited by 361 · see citing works
RetractedThe immunology of multiple sclerosis
Attfield, K. E., Jensen, L. T., Kaufmann, M., Friese, M. A., & Fugger, L. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00718-z · Cited by 380 · see citing works
Mining the microbiota for microbial and metabolite-based immunotherapies
Skelly, A. N., Sato, Y., Kearney, S., & Honda, K. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0144-5 · Cited by 306 · see citing works
Self-citationRapid gut dysbiosis induced by stroke exacerbates brain infarction in turn
Xu, K., Gao, X., Xia, G., Chen, M., Zeng, N., Wang, S., You, C., Tian, X., Di, H., Tang, W., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-323263 · Cited by 308 · see citing works
TH17 cell heterogeneity and its role in tissue inflammation
Schnell, A., Littman, D. R., & Kuchroo, V. K. (2023) · Nature Immunology · doi:10.1038/s41590-022-01387-9 · Cited by 286 · see citing works
Rethinking healthy eating in light of the gut microbiome
Armet, A. M., Deehan, E. C., O’Sullivan, A. F., Mota, J. F., Field, C. J., Prado, C. M., Lucey, A. J., & Walter, J. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.04.016 · Cited by 252 · see citing works
Sun, J., Zhang, Y., Kong, Y., Ye, T., Yu, Q., Kumaran Satyanarayanan, S., Su, K.-P., & Liu, J. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2022.08.003 · Cited by 255 · see citing works
Impacts of microbiome metabolites on immune regulation and autoimmunity
Haase, S., Haghikia, A., Wilck, N., Müller, D. N., & Linker, R. A. (2018) · Immunology · doi:10.1111/imm.12933 · Cited by 239 · see citing works
Leveraging diet to engineer the gut microbiome
Wolter, M., Grant, E. T., Boudaud, M., Steimle, A., Pereira, G. V., Martens, E. C., & Desai, M. S. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00512-7 · Cited by 211 · see citing works
Human immune diversity: from evolution to modernity
Liston, A., Humblet-Baron, S., Duffy, D., & Goris, A. (2021) · Nature Immunology · doi:10.1038/s41590-021-01058-1 · Cited by 187 · see citing works
Association of metabolic syndrome and chronic kidney disease
Scurt, F. G., Ganz, M. J., Herzog, C., Bose, K., Mertens, P. R., & Chatzikyrkou, C. (2024) · Obesity Reviews · doi:10.1111/obr.13649 · Cited by 155 · see citing works
Sodium in the microenvironment regulates immune responses and tissue homeostasis
Müller, D. N., Wilck, N., Haase, S., Kleinewietfeld, M., & Linker, R. A. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-018-0113-4 · Cited by 149 · see citing works
Self-citationPan, R., Wang, L., Xu, X., Chen, Y., Wang, H., Wang, G., Zhao, J., & Chen, W. (2022) · Nutrients · doi:10.3390/nu14183704 · Cited by 149 · see citing works
Production of Indole-3-Lactic Acid by Bifidobacterium Strains Isolated fromHuman Infants
Sakurai, T., Odamaki, T., & Xiao, J.-Z. (2019) · Microorganisms · doi:10.3390/microorganisms7090340 · Cited by 129 · see citing works
Immunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126 · see citing works
Recent advances in modulation of cardiovascular diseases by the gut microbiota
Masenga, S. K., Hamooya, B., Hangoma, J., Hayumbu, V., Ertuglu, L. A., Ishimwe, J., Rahman, S., Saleem, M., Laffer, C. L., Elijovich, F., et al. (2022) · Journal of Human Hypertension · doi:10.1038/s41371-022-00698-6 · Cited by 121 · see citing works
Medina-Rodriguez, E. M., Madorma, D., O’Connor, G., Mason, B. L., Han, D., Deo, S. K., Oppenheimer, M., Nemeroff, C. B., Trivedi, M. H., Daunert, S., et al. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.19090960 · Cited by 110 · see citing works
<i>Limosilactobacillus reuteri</i> - a probiotic gut commensal with contextual impact on immunity
Lee, A. H., Rodriguez Jimenez, D. M., & Meisel, M. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2451088 · Cited by 66 · see citing works
Bilal, M., Ashraf, S., & Zhao, X. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.931458 · Cited by 58 · see citing works
Bartley, A., Yang, T., Arocha, R., Malphurs, W. L., Larkin, R., Magee, K. L., Vickroy, T. W., & Zubcevic, J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01593 · Cited by 44 · see citing works
Whole brain radiotherapy induces cognitive dysfunction in mice: key role of gut microbiota
Luo, X.-X., Yang, C., Zhan, G.-F., Li, S., Hua, D.-Y., Luo, A.-L., & Yuan, X.-L. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05520-0 · Cited by 23 · see citing works
- Authors
- Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., Haase, S., Mähler, A., Balogh, A., Markó, L., Vvedenskaya, O., Kleiner, F. H., Tsvetkov, D., Klug, L., Costea, P. I., Sunagawa, S., Maier, L., Rakova, N., Schatz, V., Neubert, P., Frätzer, C., Krannich, A., Gollasch, M., Grohme, D. A., Côrte-Real, B. F., Gerlach, R. G., Basic, M., Typas, A., Wu, C., Titze, J. M., Jantsch, J., Boschmann, M., Dechend, R., Kleinewietfeld, M., Kempa, S., Bork, P., Linker, R. A., Alm, E. J., & Müller, D. N.
- Affiliations
- Max Delbrück Center (DE)
- Massachusetts Institute of Technology (US)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- European Molecular Biology Laboratory (DE)
- ETH Zurich (CH)
- University Hospital Regensburg (DE)
- Lipidomix (Germany) (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Technische Universität Dresden (DE)
- Robert Koch Institute (DE)
- Medizinische Hochschule Hannover (DE)
- National Institutes of Health (US)
- Vanderbilt University (US)
- Center for Regenerative Therapies Dresden (DE)
- Corresponding author
- Alm, Eric J.
- Müller, Dominik N.
- ORCID
- Wilck, Nicola
- Matus, Mariana G.
- Kearney, Sean M.
- Olesen, Scott W.
- Bartolomaeus, Hendrik
- Haase, Stefanie
- Mähler, Anja
- Markó, Lajos
- Vvedenskaya, Olga
- Kleiner, Friedrich H.
- Tsvetkov, Dmitry
- Klug, Lars
- Costea, Paul I.
- Sunagawa, Shinichi
- Maier, Lisa
- Rakova, Natalia
- Schatz, Valentin
- Neubert, Patrick
- Krannich, Alexander
- Gollasch, Maik
- Gerlach, Roman G.
- Basic, Marijana
- Typas, Athanasios
- Wu, Chuan
- Titze, Jens M.
- Jantsch, Jonathan
- Boschmann, Michael
- Dechend, Ralf
- Kleinewietfeld, Markus
- Kempa, Stefan
- Linker, Ralf A.
- Alm, Eric J.
- Müller, Dominik N.
- Venue
- Nature
- Published
- 2017-11
- Volume
- 551
- Issue
- 7682
- Pages
- 585-589
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6070150
- OpenAlex
- W2769170966
- Cited by
- 1,310
- References
- 78
- Citations by year
- 2026: 104 · 2025: 156 · 2024: 158 · 2023: 148 · 2022: 196 · 2021: 181 · 2020: 159 · 2019: 125 · 2018: 77 · 2017: 6
- FWCI
- 41.01
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Keywords
- high-salt diet, gut microbiota, Lactobacillus murinus, Th17 cells, experimental autoimmune encephalomyelitis, salt-sensitive hypertension, autoimmunity, indole metabolites, gut-immune axis, blood pressure, dietary salt
- MeSH terms
- Gastrointestinal Microbiome, Animals, Blood Pressure, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Feces, Humans, Hypertension, Indoleacetic Acids, Indoles, Intestines, Lactobacillus, Lymphocyte Activation, Male, Pilot Projects, Sodium Chloride, Symbiosis, Tryptophan, Autoimmunity, Lymphocyte Count, Mice, Th17 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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