Kidney Week

Abstract: FR-PO1005

Lactobacillus acidophilus KBL409 Protects Against Kidney Injury via Improving Mitochondrial Function with CKD

Session Information

• CKD Mechanisms: From Mendel to Mars
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Ryu, Jaejin, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Jaejin Ryu,

• Nam, Ki heon, Division of Integrated Medicine, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Ki heon Nam,

• Nam, Boyoung, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Boyoung Nam,

• Kim, Gyu Ri, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Gyu Ri Kim,

• Ko, Ye Eun, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Ye Eun Ko,

• Kim, Hyung Woo, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Hyung Woo Kim,

• Park, Jung Tak, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Jung Tak Park,

• Yoo, Tae-Hyun, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Tae-Hyun Yoo,

• Kang, Shin-Wook, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Shin-Wook Kang,

• Han, Seung Hyeok, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)

Seung Hyeok Han,

Background

Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Animal studies have shown that dysregulated gut microbiota can alter mitochondria metabolism of intestinal mucosa cells, leading to mitochondrial dysfunction. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.

Methods

KBL409 was selected because this strain was proved to maintain intestinal integrity and reduce p-cresyl sulfate level in vitro in prior experiments. An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 10⁹ CFU daily. We isolated primary mouse TECs and treated them with TGF-β (10 ng/ml) or p-cresyl sulfate (0.5mM) and sodium butyrate (10μM), a short-chain fatty acid that is considered the end products of commensal bacteria.

Results

There were prominent structural alterations in CKD mice and KBL409 administration significantly attenuated renal fibrosis. Transcript and protein expression levels of PGC-1α, a key regulator of mitochondrial biogenesis, were significantly decreased in CKD mice, which were restored by KBL409. There were concomitant changes in mitochondrial content and mitochondrial dynamic-related proteins in response to KBL409. In addition, mice with KBL administration showed improvement in fatty acid oxidation defect and mitochondrial structure compared with CKD mice. In vitro, TGF-β or p-cresyl sulfate treatment in TECs recapitulated the findings of in vivo study and these alterations were reversed by butyrate administration. Mitochondrial function assay showed that butyrate significantly improved mitochondrial respiration, fatty acid oxidation defect, oxidative phosphorylation, and ATP production in TGF-β- or p-cresyl sulfate-treated TECs.

Conclusion

This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.