Cited by 126Gut microbiota and healthSodium Intake and HealthGastrointestinal motility and disorders

Enteric dysbiosis-linked gut barrier disruption triggers early renal injury induced by chronic high salt feeding in mice

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Hu, Jingjuan, Luo, Haihua, Wang, Jieyan, Tang, Wenli, Lu, Junqi, Wu, Shan, Xiong, Zhi, Yang, Guizhi +6 more·2017·Experimental & Molecular Medicine

Abstract

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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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
Venue
Experimental & Molecular Medicine
Published
2017-08
Volume
49
Issue
8
Pages
e370-e370
ISSN
  • 1226-3613 (ISSN-L)
  • 2092-6413
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
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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