<em>Lactobacillus</em> spp. reduces ethanol‑induced liver oxidative stress and inflammation in a mouse model of alcoholic steatohepatitis

Hsieh,Pei-Shan; Chen,Ching-Wei; Kuo,Yi-Wei; Ho,Hsieh-Hsun

doi:10.3892/etm.2021.9619

Lactobacillus spp. reduces ethanol‑induced liver oxidative stress and inflammation in a mouse model of alcoholic steatohepatitis

Authors:
- Pei-Shan Hsieh
- Ching-Wei Chen
- Yi-Wei Kuo
- Hsieh-Hsun Ho
View Affiliations

Affiliations: Glac Biotech Co., Ltd., Tainan 74442, Taiwan, R.O.C.
Published online on: January 7, 2021 https://doi.org/10.3892/etm.2021.9619
Article Number: 188
Copyright: © Hsieh 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

Alcoholic steatohepatitis (ASH) is a complex multifactorial disease that can lead to liver fibrosis and cirrhosis if not treated promptly. Alcohol‑induced oxidative stress and inflammation are the main factors that cause steatohepatitis and liver injury; however, probiotic bacteria in the gastrointestinal tract have been revealed to regulate immune responses and reduce oxidative stress, suggesting that functional probiotics could help to prevent ASH and liver injury. Despite numerous reports on the interactions between ASH and probiotics, the mechanisms underlying probiotic‑mediated liver protection remain unknown. Therefore, the aim of the present study was to screen probiotics with high antioxidant capacity and investigate the ability of different probiotic combinations to reduce alcoholic liver disease (ALD) in a mouse model. It was identified that Lactobacillus plantarum (TSP05), Lactobacillus fermentum (TSF331) and Lactobacillus reuteri (TSR332) neutralized free radicals and displayed high antioxidant activity in vitro. In addition, these three functional probiotic strains protected mice from alcohol‑induced liver injury in vivo. Mice treated with the probiotics demonstrated significantly lower alanine aminotransferase, aspartate aminotransferase and triglyceride levels, which were associated with the downregulation of the proinflammatory cytokines TNF‑α and IL‑6. Furthermore, probiotic treatment upregulated glutathione and glutathione peroxidase activity, which are bioindicators of oxidative stress in the liver. Collectively, the present results indicated that Lactobacillus strains TSP05, TSF331 and TSR332 reduced oxidative stress and inflammatory responses, thus preventing ASH development and liver injury.

View Figures

View References

1	Rehm J and Shield KD: Global alcohol-attributable deaths from cancer, liver cirrhosis, and injury in 2010. Alcohol Res. 35:174–183. 2013.PubMed/NCBI
2	World Health Organization: Global status report on alcohol and health 2014. http://www.who.int/substance_abuse/publications/global_alcohol_report/msb_gsr_2014_1.pdf.
3	World Health Organization: Global status report on alcohol and health 2018. https://apps.who.int/iris/bitstream/handle/10665/274603/9789241565639-eng.pdf.
4	Bajaj JS: Alcohol, liver disease and the gut microbiota. Nat Rev Gastroenterol Hepatol. 16:235–246. 2019.PubMed/NCBI View Article : Google Scholar
5	Lieber CS: Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. Adv Pharmacol. 38:601–628. 1996.PubMed/NCBI View Article : Google Scholar
6	Li F, Duan K, Wang C, McClain C and Feng W: Probiotics and alcoholic liver disease: Treatment and potential mechanisms. Gastroent Res Pract. 2016(5491465)2016.PubMed/NCBI View Article : Google Scholar
7	Gu Z, Liu Y, Hu S, You Y, Li W and Wang Y: Probiotics for alleviating alcoholic liver injury. Gastroent Res Pract. 2019(9097276)2019.PubMed/NCBI View Article : Google Scholar
8	Schnabl B and Brenner DA: Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 146:1513–1524. 2014.PubMed/NCBI View Article : Google Scholar
9	Zhou Z and Zhong W: Targeting the gut barrier for the treatment of alcoholic liver disease. Liver Res. 1:197–207. 2017.PubMed/NCBI View Article : Google Scholar
10	Kirpich IA, Solovieva NV, Leikhter SN, Shidakova NA, Lebedeva OV, Sidorov PI, Bazhukova TA, Soloviev AG, Barve SS, McClain CJ and Cave M: Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: A pilot study. Alcohol. 42:675–682. 2008.PubMed/NCBI View Article : Google Scholar
11	Forsyth CB, Farhadi A, Jakate SM, Tang Y, Shaikh M and Keshavarzian A: Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis. Alcohol. 43:163–172. 2009.PubMed/NCBI View Article : Google Scholar
12	Wang Y, Gao J, Zhang J and Hu Y: Lactobacillus rhamnosus B10 treatment ameliorates ethanol-induced mouse liver injury by antioxidant pathways. Food Sci. 33:270–274. 2012.
13	Hiraishi A: Direct automated sequencing of 16S rDNA amplified by polymerase chain reaction from bacterial cultures without DNA purification. Lett Appl Microbiol. 15:210–213. 1992.PubMed/NCBI View Article : Google Scholar
14	Lane DJ: 16S/23S rRNA sequencing. In: Nucleic acid techniques in bacterial systematics. Stackebrandt E and Goodfellow M (eds.) John Wiley and Sons, New York, pp115-175, 1991.
15	Weisburg WG, Barns SM, Pelletier DA and Lane DJ: 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol. 173:697–703. 1991.PubMed/NCBI View Article : Google Scholar
16	Xing J, Wang G, Zhang Q, Liu X, Gu Z, Zhang H, Chen YQ and Chen W: Determining antioxidant activities of lactobacilli cell-free supernatants by cellular antioxidant assay: A comparison with traditional methods. PLoS One. 10(e0119058)2015.PubMed/NCBI View Article : Google Scholar
17	Benzie IFF and Strain JJ: Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol. 299:15–27. 1999.PubMed/NCBI View Article : Google Scholar
18	Hyronimus B, Le Marrec C, Hadj Sassi A and Deschamps A: Acid and bile tolerance of spore-forming lactic acid bacteria. Int J Food Microbiol. 61:193–197. 2000.PubMed/NCBI View Article : Google Scholar
19	Hassanzadazar H, Ehsani A, Mardani K and Hesari J: Investigation of antibacterial, acid and bile tolerance properties of lactobacilli isolated from Koozeh cheese. Vet Res Forum. 3:181–185. 2012.PubMed/NCBI
20	Lieber CS and DeCarli LM: Liquid diet technique of ethanol administration: 1989 update. Alcohol Alcohol. 24:197–211. 1989.PubMed/NCBI
21	Guo R and Ren J: Alcohol and acetaldehyde in public health: From marvel to menace. Int J Environ Res Public Health. 7:1285–1301. 2010.PubMed/NCBI View Article : Google Scholar
22	Tuma DJ and Casey CA: Dangerous byproducts of alcohol breakdown-focus on adducts. Alcohol Res Health. 27:285–290. 2003.PubMed/NCBI
23	Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW and Feng Y: The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci. 16:26087–26124. 2015.PubMed/NCBI View Article : Google Scholar
24	Mallikarjuna K, Shanmugam KR, Nishanth K, Wu MC, Hou CW, Kuo CH and Reddy KS: Alcohol-induced deterioration in primary antioxidant and glutathione family enzymes reversed by exercise training in the liver of old rats. Alcohol. 44:523–529. 2010.PubMed/NCBI View Article : Google Scholar
25	Dey A and Lakshmanan J: The role of antioxidants and other agents in alleviating hyperglycemia mediated oxidative stress and injury in liver. Food Funct. 4:1148–1184. 2013.PubMed/NCBI View Article : Google Scholar
26	Pompella A, Visvikis A, Paolicchi A, De Tata V and Casini AF: The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol. 66:1499–1503. 2003.PubMed/NCBI View Article : Google Scholar
27	Muthukumar K, Rajakumar S, Sarkar MN and Nachiappan V: Glutathione peroxidase3 of Saccharomyces cerevisiae protects phospholipids during cadmium-induced oxidative stress. Antonie van Leeuwenhoek. 99:761–771. 2011.PubMed/NCBI View Article : Google Scholar
28	Nanji AA, Khettry U and Sadrzadeh SMH: Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease). Exp Biol Med. 205:243–247. 1994.PubMed/NCBI View Article : Google Scholar
29	Banerjee A and Dhar P: Amalgamation of polyphenols and probiotics induce health promotion. Crit Rev Food Sci Nutr. 59:2903–2926. 2019.PubMed/NCBI View Article : Google Scholar
30	Cortés-Martín A, Selma MV, Tomás-Barberán FA, González-Sarrías A and Espín JC: Where to look into the puzzle of polyphenols and health? The postbiotics and gut microbiota associated with human metabotypes. Mol Nutr Food Res. 64(e1900952)2020.PubMed/NCBI View Article : Google Scholar
31	Soto-Alarcon SA, Valenzuela R, Valenzuela A and Videla LA: Liver protective effects of extra virgin olive oil: Interaction between its chemical composition and the cell-signaling pathways involved in protection. Endocr Metab Immune Disord Drug Targets. 18:75–84. 2018.PubMed/NCBI View Article : Google Scholar
32	Valenzuela R, Illesca P, Echeverría F, Espinosa A, Rincón-Cervera MA, Ortiz M, Hernandez-Rodas MC, Valenzuela A and Videla LA: Molecular adaptations underlying the beneficial effects of hydroxytyrosol in the pathogenic alterations induced by a high-fat diet in mouse liver: PPAR-α and Nrf2 activation, and NF-κB down-regulation. Food Funct. 8:1526–1537. 2017.PubMed/NCBI View Article : Google Scholar
33	Hernández-Rodas MC, Valenzuela R, Echeverría F, Rincón-Cervera MA, Espinosa A, Illesca P, Muñoz P, Corbari A, Romero N, Gonzalez-Mañan D and Videla LA: Supplementation with docosahexaenoic acid and extra virgin olive oil prevents liver steatosis induced by a high-fat diet in mice through PPAR-α and Nrf2 upregulation with concomitant SREBP-1c and NF-κB downregulation. Mol Nutr Food Res: 61, 2017. doi: 10.1002/mnfr.201700479.
34	Bull-Otterson L, Feng W, Kirpich I, Wang Y, Qin X, Liu Y, Gobejishvili L, Joshi-Barve S, Ayvaz T, Petrosino J, et al: Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment. PLoS One. 8(e53028)2013.PubMed/NCBI View Article : Google Scholar
35	Kim BK, Lee IO, Tan PL, Eor JY, Hwang JK and Kim SH: Protective effect of Lactobacillus fermentum LA12 in an alcohol-induced rat model of alcoholic steatohepatitis. Korean J Food Sci Anim Resour. 37:931–939. 2017.PubMed/NCBI View Article : Google Scholar
36	Chiu WC, Huang YL, Chen YL, Peng HC, Liao WH, Chuang HL, Chen JR and Yang SC: Synbiotics reduce ethanol-induced hepatic steatosis and inflammation by improving intestinal permeability and microbiota in rats. Food Funct. 6:1692–1700. 2015.PubMed/NCBI View Article : Google Scholar
37	Wang F, Zhang YJ, Zhou Y, Li Y, Zhou T, Zheng J, Zhang JJ, Li S, Xu DP and Li HB: Effects of beverages on alcohol metabolism: Potential health benefits and harmful impacts. Int J Mol Sci. 17(354)2016.PubMed/NCBI View Article : Google Scholar
38	Enomoto N, Yamashina S, Kono H, Schemmer P, Rivera CA, Enomoto A, Nishiura T, Nishimura T, Brenner DA and Thurman RG: Development of a new, simple rat model of early alcohol-induced liver injury based on sensitization of Kupffer cells. Hepatology. 29:1680–1689. 1999.PubMed/NCBI View Article : Google Scholar
39	Klop B, do Rego AT and Cabezas MC: Alcohol and plasma triglycerides. Curr Opin Lipidol. 24:321–326. 2013.PubMed/NCBI View Article : Google Scholar
40	Varella Morandi Junqueira-Franco M, Ernesto Troncon L, Garcia Chiarello P, do Rosário Del Lama Unamuno M, Afonso Jordao A and Vannucchi H: Intestinal permeability and oxidative stress in patients with alcoholic pellagra. Clin Nutr. 25:977–983. 2006.PubMed/NCBI View Article : Google Scholar