Exp Mol Med.  2017 Aug;49(8):e370. 10.1038/emm.2017.122.

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

• 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

• KMID: 2389298
• DOI: http://doi.org/10.1038/emm.2017.122

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.

MeSH Terms

Animals
Bacteria
Bacterial Translocation
Blood Pressure
Drinking Water
Dysbiosis
Enterobacteriaceae
Gastrointestinal Microbiome
Gene Expression
Hypertension
Intestines
Kidney
Mice*
Microbiota
Permeability
Risk Factors
Drinking Water