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Related Experiment Video

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Targeting Lactobacillus johnsonii to reverse chronic kidney disease.

Hua Miao1, Fei Liu2,3,4, Yan-Ni Wang1

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Signal Transduction and Targeted Therapy
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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.

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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.