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논문분류	춘계학술대회 초록집
제목	Probiotics with Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial dynamics and metabolism
저자	JIMIN PARK, Bo Young Nam, Ki Uk Lee, Seok Cheon Song, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, GwangPyo Ko, Tae-Wook Nam, Seung Hyeok Han
출판정보	2020; 2020(1):
키워드	Probiotics \| chronic kidney disease \| short-chain fatty acid \| mitochondria
초록	Animal studies have shown that dysregulated gut microbiota can alter mitochondria metabolism of intestinal mucosa cells, leading to mitochondrial dysfunction. Here, we evaluated whether administration of Lactobacillus acidophilus KBL409 can improve mitochondria function in kidney tubular epithelial cells (TECs) and attenuate kidney injury in animal CKD model. KBL409 was selected because this strain was proved to maintain intestinal integrity and reduce p-cresyl sulfate level in vitro in prior experiments. In vivo animal model of chronic kidney disease (CKD) was created by feeding 0.2% adenine diet to C57BL/6 mice for 4 weeks. The probiotics with Lactobacillus acidophilus KBL409 at a dose of 1x109 CFU per day were administered by oral gavage during the same period. 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. 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. This study demonstrates that probiotic supplementation with Lactobacillus acidophilus KBL409 can provide renal protective effects by improving mitochondrial function.
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