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Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 21 citations

PubMed: 39098923 DOI: 10.1038/s41392-024-01913-1

Targeting Lactobacillus johnsonii to reverse chronic kidney disease.

Signal Transduct Target Ther 9(1):195

Authors: Hua Miao, Fei Liu, Yan-Ni Wang, Xiao-Yong Yu, Shougang Zhuang, Yan Guo, Nosratola D Vaziri, Shi-Xing Ma, Wei Su, You-Quan Shang, Ming Gao, Jin-Hua Zhang, Li Zhang, Ying-Yong Zhao, Gang Cao

Affiliations

  • School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China. State Key Laboratory of Kidney Diseases, First Medical Center of Chinese PLA General Hospital, Beijing, China. Department of Urology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Department of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, Xi'an, Shaanxi, China.
  • Department of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, RI, USA.
  • Department of Public Health and Sciences, University of Miami, Miami, FL, USA.
  • School of Medicine, University of California Irvine, Irvine, CA, USA.
  • Department of Nephrology, Baoji Central Hospital, Baoji, Shaanxi, China.
  • Department of Nephrology, Xi'an Peoples Hospital, Xi'an, Shaanxi, China.
  • School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. State Key Laboratory of Kidney Diseases, First Medical Center of Chinese PLA General Hospital, Beijing, China.
  • School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Abstract

Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1-5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.

MeSH

Kidney Diseases, Cells, Serum, Kidney, Lactobacillus Johnsonii, Signal Transduction, Lactobacillus, Therapeutics

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