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5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
Targeting Lactobacillus johnsonii to reverse chronic kidney disease
Hua Miao1, Fei Liu2,3,4, Yan-Ni Wang1
1School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Gut microbial dysbiosis links to chronic kidney disease (CKD) progression. Supplementing Lactobacillus johnsonii and indole-3-aldehyde shows potential for CKD treatment by modulating the aryl hydrocarbon receptor pathway.
Area of Science:
- Microbiology
- Nephrology
- Metabolomics
Background:
- Gut microbial dysbiosis is implicated in chronic kidney disease (CKD) progression.
- Current therapies for progressive CKD remain limited.
- Understanding microbial metabolites' role in kidney disease is crucial.
Purpose of the Study:
- To identify specific gut microbes associated with CKD progression.
- To investigate the renoprotective effects of Lactobacillus johnsonii and indole-3-aldehyde.
- To elucidate the underlying mechanisms involving the aryl hydrocarbon receptor (AHR) pathway.
Main Methods:
- Microbiomic analysis of 480 participants (healthy controls and CKD stages 1-5).
- In vivo studies using adenine-induced CKD, unilateral ureteral obstruction (UUO), and 5/6 nephrectomy (NX) rat models.
- In vitro studies using cultured HK-2 cells.
- Supplementation with L. johnsonii and indole-3-aldehyde (IAld).
- Assessment of kidney lesions, clinical markers, and AHR signaling.
Main Results:
- Lactobacillus johnsonii abundance correlated with CKD progression and kidney markers.
- L. johnsonii supplementation and IAld treatment ameliorated kidney lesions in CKD models.
- IAld suppressed AHR signaling, demonstrating a renoprotective effect.
- L. johnsonii attenuated kidney injury by increasing serum IAld and suppressing AHR signaling.
Conclusions:
- Targeting L. johnsonii offers a potential therapeutic strategy for reversing CKD.
- Microbial tryptophan metabolism, via IAld and AHR signaling, plays a significant role in kidney disease.
- This study identifies novel pathways for CKD prophylaxis and treatment.
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