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http://dx.doi.org/10.5851/kosfa.2017.37.6.931

Protective Effect of Lactobacillus fermentum LA12 in an Alcohol-Induced Rat Model of Alcoholic Steatohepatitis  

Kim, Byoung-Kook (Department of Biotechnology & Department of Biomaterials Science and Engineering, Yonsei University)
Lee, In-Ock (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology)
Tan, Pei-Lei (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology)
Eor, Ju-Young (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology)
Hwang, Jae-Kwan (Department of Biotechnology & Department of Biomaterials Science and Engineering, Yonsei University)
Kim, Sae-Hun (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology)
Publication Information
Food Science of Animal Resources / v.37, no.6, 2017 , pp. 931-939 More about this Journal
Abstract
Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.
Keywords
alcoholic steatohepatitis; probiotics; Lactobacillus fermentum LA12; intestinal permeability; inflammation; oxidative stress; liver health;
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1 Lin, C. P., Chuang, W. C., Lu, F. J., and Chen, C. Y. (2017) Antioxidant and anti-inflammatory effects of hydrogen -rich water alleviate ethanol-induced fatty liver in mice. World J. Gastroenterol. 23, 4920-4934.   DOI
2 Lin, S., Chung, P., Wu, Y., Fung, C., Hsu, C., and Chen, L. (2017) Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell activation and Klebsiella pneumoniae liver translocation. PLoS One 12, e0177269.   DOI
3 Louvet, A. and Mathurin, P. (2015) Alcoholic liver disease: Mechanisms of injury and targeted treatment. Nat. Rev. Gastroenterol. Hepatol. 12, 231-242.   DOI
4 Lu, K. H., Liu, C. T., Raghu, R., and Sheen, L. Y. (2012) Therapeutic potential of Chinese herbal medicines in alcoholic liver disease. J. Tradit. Complement. Med. 2, 115-122.   DOI
5 Mathruin, P., Beuzin, F., Louvet, A., Carrie-Ganne, N., Balian, A., Trinchet, J. C., Dalsoglio, D., Prevot, S., and Naveau, S. (2007) Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features. Aliment. Pharmacol. Ther. 25, 1047-1954.   DOI
6 Nosova, T., Jokelainen, K., Kaihovaara, P., Jousimies-Somer, H., and Salaspuro, M. (1998) Characteristics of aldehyde dehydrogenases of certain aerobic bacteria representing human colonic flora. Alcohol. 33, 273-280.
7 Peterson, L.W. and Artis, D. (2014) Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14, 141-153.   DOI
8 Purohit, V., Bode, J. C., Bode, C., Brenner, D. A., Choudhry, M. A., Hamilton, F., Kang, Y. J., Keshavarzian, A., Rao, R., Sartor, R. B., Swanson, C., and Turner, J. R. (2008) Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol 42, 349-361.   DOI
9 Ramaiah, S. K. and Jaeschke, H. (2007) Role of neutrophils in the pathogenesis of acute inflammatory liver injury. Toxicol. Pathol. 35, 757-766.   DOI
10 Rao, R. K., Seth, A., and Sheth, P. (2004) Recent advances in alcoholic liver disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am. J. Physiol. Gastrointest. Liver Physiol. 286, 881-884.   DOI
11 Rao, R. (2015) Endotoxemia and gut barrier dysfunction in alcoholic liver disease. Hepatology 50, 638-644.
12 Segawa, S., Wakita, Y., Hirata, H., and Watari, J. (2008) Oral administration of heat-killed Lactobacillus brevis SBC8803 ameliorates alcoholic liver disease in ethanol-containing dietfed C57BL/6N mice. Int. J. Food Microbiol. 128, 371-377.   DOI
13 Bang, H. A., Kwon, Y. H., Lee, M. J., and Lee, W. C. (2015) Trends in the epidemiological aspects and mortality of alcoholic liver disease in Korea in the decade between 2000 and 2009. J. Clin. Med. Res. 7, 91-96.   DOI
14 Frazier, T. H., Stocker, A. M., Kershner, N. A., Marsano, L. S., and McClain, C. J. (2011) Treatment of alcoholic liver disease. Therap. Adv. Gastroenterol. 4, 63-81.   DOI
15 Forsyth, C. B., Farhadi, A., Jakate, S. M., Tang, Y., Shaikh, M., and Keshavarzian, A. (2009) 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.   DOI
16 Tang, Y., Forsyth, C. B., Farhadi, A., Rangan, J., Jakate, S., Shaikh, M., Banan, A., Fields, J. Z., and Keshavarzian, A. (2009b) Nitric oxide mediated intestinal injury is required for alcohol-induced gut leakiness and liver damage. Alcohol Clin. Exp. Res. 33, 1220-1230.   DOI
17 Szabo, G. (2015) Gut-liver axis in alcoholic liver disease. Gastroenterology 148, 30-36.   DOI
18 Tang, Y., Banan, A., Forsyth, C. B., Fields, J. Z., Lau, C. K., Zhang, L. J., and Keshavarzian, A. (2008) Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease. Alcohol Clin. Exp. Res. 32, 355-364.   DOI
19 Tang, Y., Forsyth, C. B., Banan, A., Fields, J. Z., and Keshavarzian, A. (2009a) Oats supplementation prevents alcohol-induced gut leakiness in rats by preventing alcohol-induced oxidative tissue damage. J. Pharmacol. Exp. Ther. 329, 952-958.   DOI
20 Wang, F., Zhang, Y. J., Zhou,Y., Li, Y., Zhou, T., Zheng, J., Zhang, J. J., Li, S., Xu, D. P., and Li, H. B. (2016) Effects of beverages on alcohol metabolisms: Potential health benefits and harmful impacts. Int. J. Mol. Sci.17, 354.   DOI
21 Leclercq, S., de Timary, P., Delzenne, N. M., and Starkel., P. (2017) The link between inflammation, bugs, the intestine and the brain in alcohol dependence. Transl. Psychiatry 7, e1048.   DOI
22 World Health Organization. (2014) Global status report on alcohol and health. WHO Press, Switzerland, pp. 1-25.
23 Zhou, Z., Wang, L., Song, Z., Lambert, J. C., McClain, C. J., and Kang, J. (2003) A critical involvement of oxidative stress in acute alcohol-induced hepatic TNF-${\alpha}$ production. Am. J. Pathol. 163, 1137-1146.   DOI
24 Hartsock, A. and Nelson, W.J. (2008) Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim. Biophys. Acta 1778, 660-669.   DOI
25 Hill, C., Guatner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., Morelli, L., Canani, R. B., Flint, H. J., Salminen, S., Calder, P. C., and Sanders, M. E. (2014) Expert consensus document: The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11, 506-514.   DOI
26 Keshavarzian, A., Holmes, E. W., Patel, M., Iber, F., Fields, J. Z., and Pethkar, S. (1999) Leaky gut in alcoholic cirrhosis: A possible mechanism for alcohol-induced liver damage. Am. J. Gastroenterol. 94, 200-207.   DOI
27 Lee, J., Yun, H. S., Cho, K. W., Oh, S., Kim, S. H., Chun, T., Kim, B., and Whang, K. Y. (2011) Evaluation of probiotic characteristics of newly isolated Lactobacillus spp.: Immune modulation and longevity. Int. J. Food Microbiol. 148, 80-86.   DOI
28 Li, X., Akhtar, S., and Choudhry, M. A. (2012) Alteration in intestine tight junction protein phosphorylation and apoptosis is associated with increase in IL-18 levels following alcohol intoxication and burn injury. Biochim. Biophys. Acta 1822, 196-203.   DOI