Butyrate modulates gut microbiota and anti-inflammatory response in attenuating cisplatin-induced kidney injury
Year: 2024
Type: article
Abstract: In our previous research, we reported that administering probiotics Lactobacillus reuteri and Clostridium butyricum (LCs) before cisplatin treatment effectively modifies structures of the gut microbiota and restore ecological balance and significantly increases butyrate levels, a process closely associated with reducing cisplatin-induced nephrotoxicity. This study aims to investigate further whether the elevation of metabolite butyrate in the gut, promoted by probiotics LCs, can effectively mitigate the nephrotoxic effects of cisplatin and the progression of renal senescence in rats. Results show that butyrate administration significantly improved kidney function and decreased renal fibrosis in a dose-dependent manner compared to the cisplatin group. Its effects were associated with reductions in inflammatory responses, evidenced by decreased levels of key inflammatory markers, including KIM-1, MPO, NOX2, F4/80, and TGF-β1, alongside increased production of the anti-inflammatory cytokine IL-10. Furthermore, the butyrate intervention ameliorated cisplatin-induced gut microbiota dysbiosis, preserving the structure and diversity of healthy microbial communities. Specifically, we observed a decrease in the abundance of Escherichia_Shigella and Blautia, alongside an increase in the abundance of the butyrate-producing genus Roseburia. Notably, Escherichia_Shigella exhibited a positive correlation with the pro-inflammatory factor MPO, while displaying a negative correlation with the anti-inflammatory cytokine IL-10. Butyrate also attenuated the cisplatin-induced expression of senescence markers p21 and p16 in kidney tissue. It alleviated the cisplatin-increased senescence-associated beta-galactosidase activity and reactive oxygen species production in SV40 MES-13 cells. These results indicate that butyrate, derived from the gut microbiota, may exert a protective effect against cisplatin-induced kidney damage by regulating microbiota balance and anti-inflammatory effects.
Source: Biomedicine & Pharmacotherapy
Authors: Wen-Jung Chen, Yng-Tay Chen, Jiunn-Liang Ko, Jian-Yuan Chen, Jun-Yao Zheng, Jiunn-Wang Liao, Chu-Chyn Ou
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,420
Awards: In Vivo and in Vitro Models, Explore the Potential Efficacy and Related Mechanisms of Lactobacillus Reuteri and Its Cell-Free Supernatant, as Well as Extracellular Vesicles, in Mitigating Chemotherapy-Induced Toxic Damage, G7580618992, Molecular Mechanism of the Protective Effect of Probiotics and Its Metaboliteon on Cisplatin-Induced Renal Senescence and Renal Fibrosis and the Study of Cisplatin, D-Methionine and Probiotics on Microbiota Metabolic Carbon Substrates
OpenAlex ID: W4404657748