Enteric dysbiosis-linked gut barrier disruption triggers early renal injury induced by chronic high salt feeding in mice
Open accessAbstract
Chronic high-salt diet-associated renal injury is a key risk factor for the development of hypertension. However, the mechanism by which salt triggers kidney damage is poorly understood. Our study investigated how high salt (HS) intake triggers early renal injury by considering the ‘gut-kidney axis’. We fed mice 2% NaCl in drinking water continuously for 8 weeks to induce early renal injury. We found that the ‘quantitative’ and ‘qualitative’ levels of the intestinal microflora were significantly altered after chronic HS feeding, which indicated the occurrence of enteric dysbiosis. In addition, intestinal immunological gene expression was impaired in mice with HS intake. Gut permeability elevation and enteric bacterial translocation into the kidney were detected after chronic HS feeding. Gut bacteria depletion by non-absorbable antibiotic administration restored HS loading-induced gut leakiness, renal injury and systolic blood pressure elevation. The fecal microbiota from mice fed chronic HS could independently cause gut leakiness and renal injury. Our current work provides a novel insight into the mechanism of HS-induced renal injury by investigating the role of the intestine with enteric bacteria and gut permeability and clearly illustrates that chronic HS loading elicited renal injury and dysfunction that was dependent on the intestine. Kidney damage caused by high salt intake is triggered by microbial imbalances and impaired inflammatory responses in the gut. Peng Chen at the Southern Medical University in Guangzhou, China, and co-workers investigated how high salt intake triggers early-stage kidney damage, a key factor in the development of high blood pressure. Chen's team fed mice with high salt levels for eight weeks and found that the diversity and amount of microbial flora in the intestines changed considerably as a result. This imbalance led to the break-down of the gut barrier, the cell layer lining the gut that prevents material passing into other organs, meaning that bacteria entered the kidneys. High salt also impaired inflammatory responses and disrupted immune system gene expression. The findings may inform future treatments for high blood pressure and kidney dysfunction.
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Susceptibility to organ injury, especially in the brain, can be modulated by the intestinal microbiota.
“Previous studies have indicated that susceptibility to organ injury, especially in the brain, could be modulated by the intestinal microbiota (9–11).”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [10]
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- Authors
- Hu, J., Luo, H., Wang, J., Tang, W., Lu, J., Wu, S., Xiong, Z., Yang, G., Chen, Z., Lan, T., Zhou, H., Nie, J., Jiang, Y., & Chen, P.
- Affiliations
- Southern Medical University (CN)
- Guangdong Pharmaceutical University (CN)
- Corresponding author
- Chen, Peng
- ORCID
- Venue
- Experimental & Molecular Medicine
- Published
- 2017-08
- Volume
- 49
- Issue
- 8
- Pages
- e370-e370
- ISSN
- 1226-3613 (ISSN-L)
- 2092-6413
- PMC
- PMC5579512
- OpenAlex
- W2749268425
- Cited by
- 126
- References
- 41
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 24 · 2023: 15 · 2022: 18 · 2021: 16 · 2020: 12 · 2019: 9 · 2018: 5
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Experimental & Molecular Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- National Natural Science Foundation of China (31500952)
- Southern Medical University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- kidney injury, gut dysbiosis, gut-kidney axis, intestinal permeability, bacterial translocation, gut barrier disruption, fecal microbiota, hypertension, non-absorbable antibiotics, intestinal inflammation, immune gene expression
- MeSH terms
- Bacillota, Gastrointestinal Microbiome, Animals, Blood Pressure, Feces, Male, Mice, Inbred C57BL, Permeability, RNA, Time Factors, Sodium Chloride, Dietary, Gene Expression Profiling, Bacteroidetes, Gastrointestinal Tract, Mice, Acute Kidney Injury, Dysbiosis
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