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.

Author(s) Lee, T.H.; Park, D.; Kim, Y.Ji; Lee, I.; Kim, S.; Oh, C.T.; Kim, J.Y.; Yang, J.; Jo, S.K.
Journal Int J Mol Med
Date Published 2020 Apr

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 salivarius 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.

DOI 10.3892/ijmm.2020.4495
ISSN 1791-244X
Citation Int J Mol Med. 2020;45(4):11301140.

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