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

Lee,Tae‑Hee; Park,Dongsun; Kim,Yang Ji; Lee,Isaac; Kim,Suae; Oh,Chang‑Taek; Kim,Joem‑Yong; Yang,Jihyun; Jo,Sang‑Kyung

doi:10.3892/ijmm.2020.4495

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

Authors:
- Tae‑Hee Lee
- Dongsun Park
- Yang Ji Kim
- Isaac Lee
- Suae Kim
- Chang‑Taek Oh
- Joem‑Yong Kim
- Jihyun Yang
- Sang‑Kyung Jo
View Affiliations

Affiliations: Department of Toxicity Evaluation, Centralbio Co., Ltd., Gimpo, Gyeonggi 31499, Republic of Korea, Department of Biology Education, Korea National University of Education, Cheongju, North Chungcheong 28173, Republic of Korea, Hoseo Toxicological Research Center, Hoseo University, Asan, Chungnam 31499, Republic of Korea, Research Institute, Research and Development Center, Green Cross WellBeing Corporation, Seongnam, Gyeonggi 13595, Republic of Korea, Department of Internal Medicine, Division of Nephrology, Korea University Medical College, Seoul 02841, Republic of Korea
Published online on: February 10, 2020 https://doi.org/10.3892/ijmm.2020.4495
Pages: 1130-1140
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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, 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.

View Figures

View References

1	Zuk A and Bonventre JV: Acute kidney injury. Annu Rev Med. 67:293–307. 2016. View Article : Google Scholar : PubMed/NCBI
2	Bellomo R, Kellum JA and Ronco C: Acute kidney injury. Lancet. 380:756–766. 2012. View Article : Google Scholar : PubMed/NCBI
3	Hsu CY, McCulloch CE, Fan D, Ordonez JD, Chertow GM and Go AS: Community-based incidence of acute renal failure. Kidney Int. 72:208–212. 2007. View Article : Google Scholar : PubMed/NCBI
4	Rahman M, Shad F and Smith MC: Acute kidney injury: A guide to diagnosis and management. Am Fam Physician. 86:631–639. 2012.PubMed/NCBI
5	Ozkok A and Edelstein CL: Pathophysiology of cisplatin-induced acute kidney injury. Bio Med Res Int. 2014:9678262014.
6	Chen YY, Chen DQ, Chen L, Liu JR, Vaziri ND, Guo Y and Zhao YY: Microbiome-metabolome reveals the contribution of gut-kidney axis on kidney disease. J Transl Med. 17:52019. View Article : Google Scholar : PubMed/NCBI
7	Gong J, Noel S, Pluznick JL, Hamad ARA and Rabb H: Gut microbiota-kidney cross-talk in acute kidney injury. Semin Nephrol. 39:107–116. 2019. View Article : Google Scholar : PubMed/NCBI
8	Pabla N and Dong Z: Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int. 73:994–1007. 2008. View Article : Google Scholar : PubMed/NCBI
9	Wang D and Lippard SJ: Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov. 4:307–320. 2005. View Article : Google Scholar : PubMed/NCBI
10	Cohen SM and Lippard SJ: Cisplatin: From DNA damage to cancer chemotherapy. Prog Nucleic Acid Res Mol Biol. 67:93–130. 2001. View Article : Google Scholar : PubMed/NCBI
11	Joyce K, Saxena S, Williams A, Damurjian C, Auricchio N, Aluotto S, Tynan H and Demain AL: Antimicrobial spectrum of the antitumor agent, cisplatin. J Antibiot (Tokyo). 63:530–532. 2010. View Article : Google Scholar
12	Taur Y and Pamer EG: Microbiome mediation of infections in the cancer setting. Genome Med. 8:402016. View Article : Google Scholar : PubMed/NCBI
13	Andrade-Oliveira V, Amano MT, Correa-Costa M, Castoldi A, Felizardo RJ, de Almeida DC, Bassi EJ, Moraes-Vieira PM, Hiyane MI, Rodas AC, et al: Gut bacteria products prevent AKI induced by ischemia-reperfusion. J Am Soc Nephrol. 26:1877–1888. 2015. View Article : Google Scholar : PubMed/NCBI
14	Barrows IR, Ramezani A and Raj DS: Gut feeling in AKI: The long arm of short-chain fatty acids. J Am Soc Nephrol. 26:1755–1757. 2015. View Article : Google Scholar : PubMed/NCBI
15	LeBlanc JG, Chain F, Martín R, Bermúdez-Humarán LG, Courau S and Langella P: Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb Cell Fact. 16:792017. View Article : Google Scholar : PubMed/NCBI
16	Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, Murayama MA, Ueda Y, Wakisaka S, Suzuki T and Suzuki N: Propionate-producing bacteria in the intestine may associate with skewed responses of IL10-producing regulatory T cells in patients with relapsing polychondritis. PLoS One. 13:e02036572018. View Article : Google Scholar : PubMed/NCBI
17	Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN and Hermoso MA: Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. 10:2772019. View Article : Google Scholar : PubMed/NCBI
18	Chen T, Kim CY, Kaur A, Lamothe L, Shaikh M, Keshavarzian A and Hamaker BR: Dietary fibre-based SCFA mixtures promote both protection and repair of intestinal epithelial barrier function in a caco-2 cell model. Food Funct. 8:1166–1173. 2017. View Article : Google Scholar : PubMed/NCBI
19	Diao H, Jiao AR, Yu B, Mao XB and Chen DW: Gastric infusion of short-chain fatty acids can improve intestinal barrier function in weaned piglets. Genes Nutr. 14:42019. View Article : Google Scholar : PubMed/NCBI
20	Meimandipour A, Hair-Bejo M, Shuhaimi M, Azhar K, Soleimani AF, Rasti B and Yazid AM: Gastrointestinal tract morphological alteration by unpleasant physical treatment and modulating role of lactobacillus in broilers. Br Poult Sci. 51:52–59. 2010. View Article : Google Scholar : PubMed/NCBI
21	Fujii H, Nishijima F, Goto S, Sugano M, Yamato H, Kitazawa R, Kitazawa S and Fukagawa M: Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress. Nephrol Dial Transplant. 24:2089–2095. 2009. View Article : Google Scholar : PubMed/NCBI
22	Wang CY, Lin PR, Ng CC and Shyu YT: Probiotics properties of lactobacillus strains isolated from the feces of breast-fed infants and Taiwanese pickled cabbage. Anaerobe. 16:578–585. 2010. View Article : Google Scholar : PubMed/NCBI
23	Fang CY, Lu JR, Chen BJ, Wu C, Chen YP and Chen MJ: Selection of uremic toxin-reducing probiotics in vitro and in vivo. J Funct Foods. 7:407–415. 2014. View Article : Google Scholar
24	McDonald JW and Pilgram TK: Nuclear expression of p53, p21 and cyclin D1 is increased in bronchioloalveolar carcinoma. Histopathology. 34:439–446. 1999. View Article : Google Scholar : PubMed/NCBI
25	Pagliari D, Piccirillo CA, Larbi A and Cianci R: The interactions between innate immunity and microbiota in gastrointestinal diseases. J Immunol Res. 2015:8982972015. View Article : Google Scholar : PubMed/NCBI
26	Ley RE, Turnbaugh PJ, Klein S and Gordon JI: Microbial ecology: Human gut microbes associated with obesity. Nature. 444:1022–1023. 2006. View Article : Google Scholar : PubMed/NCBI
27	Turnbaugh PJ and Gordon JI: The core gut microbiome, energy balance and obesity. J Physiol. 587:4153–4158. 2009. View Article : Google Scholar : PubMed/NCBI
28	Wang Y, Hoenig JD, Malin KJ, Qamar S, Petrof EO, Sun J, Antonopoulos DA, Chang EB and Claud EC: 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J. 3:944–954. 2009. View Article : Google Scholar : PubMed/NCBI
29	Jeffery IB, O'Toole PW, Öhman L, Clasesson MJ, Deane J, Quigley EM and Simre'n M: An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 61:997–1006. 2012. View Article : Google Scholar
30	Barrett E, Hayes M, O'Connor P, Gardiner G, Fitzgerald GF, Stanton C and Hill C: Salivaricin P: One of a family of two-component antilisterial bacteriocins produced by intestinal isolates of Lactobacillus salivarius. Appl Environ Microbiol. 73:3719–3723. 2007. View Article : Google Scholar : PubMed/NCBI
31	Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, Drew JC, Ilonen J, Knip M, Hyöty H, et al: Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 5:82–91. 2011. View Article : Google Scholar :
32	Ley RE, Peterson DA and Gordon JI: Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 124:837–848. 2006. View Article : Google Scholar : PubMed/NCBI
33	Wells JM, Rossi O, Meijerink M and van Baarlen P: Epithelial crosstalk at the microbiota-mucosal interface. Proc Natl Acad Sci USA. 108(Suppl 1): 4607–4614. 2011. View Article : Google Scholar
34	Bryniarski MA, Hamarneh F and Yacoub R: The role of chronic kidney disease-associated dysbiosis in cardiovascular disease. Exp Biol Med (Maywood). 244:514–525. 2019. View Article : Google Scholar
35	Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RJM and Wells JM: Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol. 298:G851–G859. 2010. View Article : Google Scholar : PubMed/NCBI
36	Vaziri ND: CKD impairs barrier function and alters microbial flora of the intestine: A major link to inflammation and uremic toxicity. Curr Opin Nephrol Hypertens. 21:587–592. 2012. View Article : Google Scholar : PubMed/NCBI
37	Mariadason JM, Barkla DH and Gibson PR: Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model. Am J Physiol. 272:G705–G712. 1997.PubMed/NCBI
38	Kendle M and Maslowski: The role of GPR43 in the immune system: A novel connection between diet, gut microbiota and immune function. University of New South Wales; Sydney: 2013
39	Nyman M: Fermentation and bulking capacity of indigestible carbohydrates: The case of inulin and oligofructose. Br J Nutr. 87(Suppl 2): 163–168. 2002. View Article : Google Scholar
40	Kotzampassi K, Giamarellos-Bourboulis EJ and Stavrou G: Obesity as a consequence of gut bacteria and diet interactions. ISRN Obes. 2014:6518952014.PubMed/NCBI
41	Wong JM, de Souza R, Kendall CW, Emam A and Jenkins DJ: Colonic health: Fermentation and short chain fatty acids. J Clin Gastroenterol. 40:235–243. 2006. View Article : Google Scholar : PubMed/NCBI
42	Pomare EW, Branch WJ and Cummings JH: Carbohydrate fermentation in the human colon and its relation to acetate concentrations in venous blood. J Clin Invest. 75:1448–1454. 1985. View Article : Google Scholar : PubMed/NCBI
43	Kim MH, Kang SG, Park JH, Yanagisawa M and Kim CH: Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 145:396–406. 2013. View Article : Google Scholar : PubMed/NCBI
44	Tedelind S, Westberg F, Kjerrulf M and Vidal A: Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: A study with relevance to inflammatory bowel disease. World J Gastroenterol. 13:2826–2832. 2007. View Article : Google Scholar : PubMed/NCBI
45	Liu T, Li J, Liu Y, Xiao N, Suo H, Xie K, Yang C and Wu C: Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-κB pathway in RAW264.7 cells. Inflammation. 35:1676–1684. 2012. View Article : Google Scholar : PubMed/NCBI
46	Tazoe H, Otomo Y, Karaki S, Kato I, Fukami Y, Terasaki M and Kuwahara A: Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res. 30:149–156. 2009. View Article : Google Scholar : PubMed/NCBI
47	Wang Y, Wu Y, Wang Y, Xu H, Mei X, Yu D and Li W: Antioxidant properties of probiotic bacteria. Nutrients. 9:521–535. 2017. View Article : Google Scholar :
48	Mishra V, Shah C, Mokashe N, Chavan R, Yadav H and Prajapati J: Probiotics as potential antioxidants: A systematic review. J Agric Food Chem. 63:3615–3626. 2015. View Article : Google Scholar : PubMed/NCBI
49	Baek SM, Kwon CH, Kim JH, Woo JS, Jung JS and Kim YK: Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal proximal tubular epithelial cells. J Lab Clin Med. 142:178–186. 2003. View Article : Google Scholar : PubMed/NCBI
50	Meijers BK and Evenepoel P: The gut-kidney axis: Indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant. 26:759–761. 2011. View Article : Google Scholar : PubMed/NCBI
51	Jourde-Chiche N, Dou L, Cerini C, Dignat-George F, Vanholder R and Brunet P: Protein-bound toxins-update 2009. Semin Dial. 22:334–339. 2009. View Article : Google Scholar : PubMed/NCBI
52	Ramezani A and Raj DS: The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 25:657–670. 2014. View Article : Google Scholar :
53	Yoshifuji A, Wakino S, Irie J, Tajima T, Hasegawa K, Kanda T, Tokuyama H, Hayashi K and Itoh H: Gut Lactobacillus protects against the progression of renal damage by modulating the gut environment in rats. Nephrol Dial Transplant. 31:401–412. 2015. View Article : Google Scholar : PubMed/NCBI