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

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 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, H 2 O 2 -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.

Assessment of Probiotic Properties of Lactobacillus salivarius Isolated From Chickens as Feed Additives

“…Our results showed that Lactobacillus salivarius supplementation enhanced immune responses to infectious bursal disease vaccine in chickens with cy treatment. This may be due to Lactobacillus salivarius enhanced the body's ability to resist oxidative stress, which has been confirmed by previous studies (28,29), and our results are consistent with these findings. In addition, we also found that Lactobacillus salivarius group exhibited an enhanced immune response after immunization compared to control group in chickens without cy treatment.…”

“…In addition to reduce the room temperature by spraying water, negative effects of heat stress can be alleviated by feeding anti-oxidative substances in poultry production ( 6 , 27 ). Previous studies have evaluated the antioxidant activity of various Lactobacillus strains and indicated that Lactobacillus salivarius showed good anti-oxidative properties ( 28 , 29 ). In the present study, Lactobacillus salivarius supplementation effectively alleviated the organ damage and enhanced anti-oxidative capacity in both acute heat stress and circular heat stress condition.…”

p-Cresol Sulfate Caused Behavior Disorders and Neurodegeneration in Mice with Unilateral Nephrectomy Involving Oxidative Stress and Neuroinflammation

“…CKD patients are frequently associated with gut dysbiosis and the elevation of circulating indoxyl sulfate and PCS [ 14 , 44 ]. Probiotics or nutritional therapy are of benefit for improving gut dysbiosis and decreasing circulating uremic toxins, oxidative stress, and inflammation [ 6 , 45 ]. Since indoxyl sulfate and PCS remain difficult to remove by hemodialysis, gut microbiota could be an alternative target for reducing the circulating indoxyl sulfate, PCS levels, and their toxicity in CKD patients, with the aim of slowing down the progression of the disease and decreasing any CNS complications.…”

The Links between Microbiome and Uremic Toxins in Acute Kidney Injury: Beyond Gut Feeling—A Systematic Review

“…In a prospective cohort study, serum indoxyl sulfate levels were also associated with mortality in hospital-acquired AKI [ 14 ]. In a murine model, suppression of indole and p-cresyl production by Lactobacillus salivarius protected against cisplatin-induced kidney injury [ 23 ].…”