Lactobacillus salivarius BP121 prevents cisplatin‑induced acute kidney injury by inhibition of uremic toxins such as indoxyl sulfate and p‑cresol sulfate via alleviating dysbiosis

Tae Hee Lee, Dongsun Park, Yang J.I. Kim, Isaac Lee, Suae Kim, Chang Taek Oh, Joem Yong Kim, Jihyun Yang, Sang Kyung Jo

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    The gut microbiota is important for maintaining the integrity of the intestinal barrier, promoting immunological tolerance and carrying out metabolic activities that have not evolved in hosts. Intestinal dysbiosis is associated with chronic kidney disease and probiotic supplementation has been shown to be beneficial. However, it is not known whether gut microorganisms-specifically, lactic acid bacteria (LAB) can protect against acute kidney injury (AKI). To address this issue, the present study investigated the effects of Lactobacillus sali‑ varius BP121, an intestinal LAB isolated from the feces of newborns, in a rat model of cisplatin-induced AKI and also in Caco-2 human intestinal epithelial cells. BP121 prevented cisplatin-induced AKI in rats, as demonstrated by decreases in inflammation and oxidative stress in kidney tissue and in serum levels of uremic toxins such as indoxyl sulfate (IS) and p-cresol sulfate (PCS). BP121 also reduced intestinal permeability, as determined using fluorescein isothiocyanate-dextran by immunohistochemical detection of tight junction (TJ) proteins such as zona occludens-1 and occludin. The abundance of Lactobacillus spp., which are beneficial intestinal flora, was increased by BP121; this was accompanied by an increase in the concentrations of short-chain fatty acids in feces. Additionally, H2O2-induced TJ protein damage was reduced in Caco-2 cells treated with BP121 culture supernatant, an effect that was reversed by the 5' AMP-activated protein kinase (AMPK) inhibitor Compound C and Toll-like receptor (TLR)4 inhibitor TLR4-IN-C34. In conclusion, this study demonstrated that L. salivarius BP121 protects against cisplatin-induced AKI by decreasing inflammation and oxidative stress and this renoprotective effect is partially mediated by modulating the gut environment and thereby suppressing IS and PCS production as well as by regulating AMPK and TLR4 dependent TJ assembly.

    Original languageEnglish
    Pages (from-to)1130-1140
    Number of pages11
    JournalInternational journal of molecular medicine
    Volume45
    Issue number4
    DOIs
    Publication statusPublished - 2020

    Keywords

    • Acute kidney injury
    • Cis-diammineplatinum (II) dichloride
    • Dysbiosis
    • Indoxyl sulfate
    • Lactic acid bacteria
    • P-cresol sulfate

    ASJC Scopus subject areas

    • Genetics

    Fingerprint

    Dive into the research topics of 'Lactobacillus salivarius BP121 prevents cisplatin‑induced acute kidney injury by inhibition of uremic toxins such as indoxyl sulfate and p‑cresol sulfate via alleviating dysbiosis'. Together they form a unique fingerprint.

    Cite this