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1 한국유가공기술과학회지 Korean J. Dairy Sci. Technol. Vol. 32. No. 1, pp. 1~6(2014) Prevention of Alcoholic Liver Disease by Using Probiotics In Ok Lee and Sae Hun Kim* Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul , Korea Abstract Probiotics have been extensively studied for their beneficial effects on human health. In particular, Lactobacillus and Bifidobacterium strains have gained considerable attention as major groups of probiotic bacteria that improve gastrointestinal health. However, emerging evidence suggests that probiotics offer benefits beyond those observed in the gut recent studies suggest that probiotics and/or their components exert favorable effects on alcoholic liver disease (ALD) pathogenesis such as decreasing intestinal permeability, inhibiting pathogenic bacteria growth, increasing the activity of alcohol metabolism enzymes, modulating the adaptive immune system, and suppressing fatty acid synthesis genes. In this review, we discuss the results of in vivo and in vitro studies that have examined the use of probiotics to prevent ALD, primarily focusing on those that explore the cellular and molecular mechanisms underlying the activities of promising probiotic strains. The evidence presented in this review could help in screening for probiotic strains that have protective effects in ALD patients and in further elucidating the mechanisms of their actions. Keywords: alcohol, acetaldehyde, alcoholic liver disease, probiotics, lactic acid bacteria (alcohol).,,. WHO 250, (15~19 ) 32, 9% (Lee et al., 2012). * Corresponding author: Sae Hun Kim, Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul , Korea. Tel: ; Fax: , saehkim@korea.ac.kr (alcoholic liver disease, ALD), (Kang, 2007). (alcoholic fatty liver), (alcoholic hepatitis), (alcoholic cirrhosis) (Park, 1995) , (Lee et al., 2012).. 1

2 2 한국유가공기술과학회지제 32 권제 1 호 (2014), (Lee et al., 2009; Mitchell et al., 1986)., (Lee et al., 2009; Tsukamoto and Towner, 1984; Lieber, 1991)..,.., %, 94.4% (Lee, 2012).. (probiotics). (lactic acid bacteria) (bifidobacterium),.,., (, 2005).. 1., 1) 20%, 80%.,. (alcohol dehydrogenase, ALD) (microsome) P-450 (cytochrome P-450 oxidase) (acetaldehyde). (aldehyde dehydrogenase, ALDH) (acetate) (Kang, 2007;, 2007:, 2003).,.. (, 2005). 2),, (Lee et al., 2009; Mitchell et al., 1986). (microtubule), (Lee et al., 2009; Lieber, 1991) Cr-EDTA, (1.99±0.53%) (5.62±2.80%) (Kim et al., 2004). 3),., TNF-α, IL-1, IL-6., (, 2005).. 10 ( ) 50% dextrose, ( ) 50%. 2, 4, 8, 10,,. lactulose mannitol, Lactulose/mannitol (L/M)., 2

3 프로바이오틱스섭취를통한알코올성간질환의완화 3 L/M. 2., 4.,. 10 (councilman body)., (Keshavarzian et al., 2009). 4),..,, (Cho et al., 2001; Keshavarzian et al., 1994)., (Lee et al., 2009; Tsukamoto and Towner, 1984; Lieber, 1991). 5) (free radical) (Cho et al., 2001; Glueck et al., 1980; Figueroa et al., 1962; Aykac et al., 1985; Kang, 2007)., (Kang, 2007)., (Cho et al., 2001; Lee et al., 2009; Rouach et al., 1983). 2. 1), (, 2003; Lee et al., 2012).,, (Kim et al,. 2008; Fuller, 1989; Lee et al., 2012). (Kim et al., 2008; Smith, 1985)., (Lee et al., 2012). 2) tight junction protein ZO-1 tight junction protein,., Lactobacillus rhamnosus GG(LGG), tight junction protein,. Caco-2 5%, 10 9 CFU/mL LGG LGG TEER(transepithelial electrical resistance) LGG TEER. TEER LGG. In vivo LGG, LGG (Wang et al., 2011). 3).,., (Purohit et al., 2008). Lactobacillus acidophilus NP51 Escherichia coli O157:H7 (Peterson et al., 2007; Younts-Dahl et al., 2005), L. acidophilus LAP5 L. fermentum LF33 Escherichia coli O157:H7 Salmonella typhimurium 150

4 4 한국유가공기술과학회지제 32 권제 1 호 (2014) (Tsai et al., 2005). 4) ADH, ALDH,. ( ) Lactobacillus Bifidobacteruim,.,,,, 22% (3.0 g/kg B.W.),,, ADH., ALDH,., (Ahn et al., 2005). 3.,., ALT 41.2±4.1, 64.7±3.8, 44.7±5.3 IU/L. 2 AST ALT. AST ALT (Ahn et al., 2005). Han (Han et al., 2005) CCl 4 Lactobacillus brevis HY7401, Lactobacillus acidophilus CSG, Bifidobacterium longum HY8001, CCl 4 ALT AST. Lactobacillus brevis, RT-PCR SREBP-1, SREBP-2 TNF-α mrna,,., (Segawa et al., 2008). 2) 66. Bifidobacterium bifidum Lactobacillus plantarum 8PA3, ALT (49.84±6.94 U/L vs ±4.67 U/L), AST(101.06±4.33 U/L vs ±7.71 U/L), GGT(171.48±26.05 vs ±18.74 U/L) (Kirpich et al., 2008). 1) TNF-α. 5% 8, 2 LGG TNF-α, (Wang et al., 2013). 2, AST ALT, AST ALT.,, AST 88.7±6.5, 114.6±7.1, 94.0±55 IU/L,,.,,., ADH, ALDH,

5 프로바이오틱스섭취를통한알코올성간질환의완화 5,.,,,.., Ahn, Y. T., Bae, J. S., Kim, Y. H., Lim, K. S. and Hun, C. S Effects of fermented milk intake on hepatic antioxidative systems in alcohol treated rats. Korean J. Food Sci. Technol. 37: Ali, K., Ashkan, F., Christopher, B. F., Jayanthi, R., Shriram, J., Maliha, S., Ali, B. and Jeremy, Z. F Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in rats. Journal of Hepatology 50: Aykac, G., Usual, M., Yalcin, S., Kocak, T. N., Sivas, A, and Oz, H The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione. glutathione peroxidase and glutathione transferase in rats. Toxico. 36: Cho, S. H., Kim, J. C. and Kim, S. W Effect of plant extracts on the activity of alcohol dehydrogenase and the antioxidation in alcohol-treated rat hepatocyte. J. Korean Soc. Food Sci. Nutr. 30: Figueroa, P. B. and Klitz, A. P Alterations of alcohol dehydrogenase and other enzyme following oral alcohol intoxication. Am. J. Clin. Nutr. 11: Fuller, R Probiotics in man and animals. J. Appl. Bacterial. 66: Gleuck, C. J., Hogg, E., Allcn, C. and Gartside, P. S Effects of alcohol ingestion on lipid and lipoprotein in normal man. Am. J. Clin. Nutr. 33: Han, S. Y., Huh, C. S., Ahn, Y. T., Lim, K. S., Baek, Y. J. and Kim, D. H Hepatoprotective effect of lactic acid bacteria, inhibitors of β-glucuronidase production against intestinal microflora. Arch. Pham. Res. 28: Kang, T. J Innate immune response on alcoholic liver disease. J. of Korean Alcohol Science 8: Keshavarzian, A., Fields, J. Z., Vaeth, J. and Holmes, E. W The differing effects of acute and chronic alcohol on gastric and intestinal permeability. Am. J. Gastro. 89: Kim, J. W., Jeon, W. K., Yun, W. J., Park, D. I., Cho, Y. K., Sung, I. K., Park, C. Y., Sohn, C. I., Kim, B. I., Kim, E. J. and Shin, M. S Intestinal permeability in patients with viral and alcoholic liver. The Korean Journal of Gastroenterology 43: Kim, S. H., Kim, D. W., Park, S. Y., Kim, J. H., Kang, G. H., Kang, H. K., Yu, D. J., Na, J. C. and Lee, S. J Effect of dietary Lactobacillus on growth performance, intestinal microflora, development of ileal villi, and intestinal mucosa in broiler chickens. J. Anim. Sci & Technol. 50: Kirpich, I. A., Solovieva, N. V., Leikhter, S. N., Shidakova, N. A., Lebedeva, O. V., Sidorov, P. I., Bazhukova, T. A., Solviev, A. G., Barve, S. S., McClain, C. J. and Cave, M Proboitics resotre bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol. 42: Lee, E. H. and Chyun, J. H Effects of Chongkukjang intake on lipid metabolism and liver function in alcoholic fatty liver rats. J. Korean Soc. Food Sci. Nutr. 38: Lee, M. R The relationship between alcohol use and drinking problems among colloge students. Journal of the Korea Academia-Industrial Cooperation Society. 13: Lee, S. E., Lee, J. H., Kim, G. S., Hong, Y. P., Noh, H. J., Park, C. G. and Kim, S. Y Effect of root extract of Lythrum salicaria L. on liver function of rat acutely administrated with alcohol. Korean J. Medicinal Crop Sci. 20: Lee, S. J., Lee, M. J., Jung, J. E., Kim, H. J. and Shambhunath, B In vitro profiling of bacterial influence and herbal applications of Lonicerae Flos on the permeability of intestinal epithelia cells. Korean Soc.

6 6 한국유가공기술과학회지제 32 권제 1 호 (2014) Food Sci. Nutr. 41: Lieber, C. S Hepatic metabolic and toxic effect of ethanol. Alcoholism Clin. Exp. Res. 15: Mitchell, M. C. and Herlong, H. F Alcohol and nutrition: Caloric value, bioenergetics, and relationship to liver damage. Ann. Rev. Nutr. 6: Park, B. C Alcohol and liver disease. Korean J. Life Science 5: Perterson, R. E., Klopfenstein, T. J., Erickson, G. E., Folmer, J., Hinkley, S., Moxley, R. A. and Smith, D. R Effect of Lactobacillus acidophilus strain NP51 on Escherichia coli O157:H7 fecal shedding and finishing performance in beef feedlot cattle. J. Food Prot. 70: 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 Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences : summary of a symposium. Alcohol. 42: Rouach, H., Clement, M., Ofanelli, M. T., Janvier, B., Nordmann, J. and Nordmann, R Hepatic lipid peroxidation and mitochondria susceptibility to peroxedation and mitochondria susceptibility to peroxidative attacks during ethanol inhalation and withdrawal. Biochem. Biophys. Acta. 753: Segawa, S., Wakita, Y., Hirata, H. and Watari, J Oral administration of heat-killed Lactobacillus brevis SBC8803 ameliorates alcoholic liver disease in ethanolcontaining diet-fed C57BL/6N mice. International Journal of Food Microbiology 128: Smith, M. W Expression of digestive and absorptive function in differentiating enterocytes. Annu. Rev. Physiol. 47: Tsai, C. C., Hsih, H. Y., Chiu, H. H., Lai, Y. Y., Liu, J. H., Yu, B. and Tsen, H. Y Antagonistic acitivity against Salmonella infection in vitro and in vivo for two Lactobacillus strains from swine and poultry. Int. J. Food Microbiol. 102: Tsukamoto, H. and Towner, S. J Ethanol induced liver fibrosis in rats fed high fat diets. Hepatology. 6: Wang, Y., Liu, Y., Kirpich, I., Ma, Z., Wang, C., Zhang, M., Suttles, J., McClain, C. and Feng, W Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflmmation in chronic alcohol-induced liver injury. Journal of Nutritional Biochemistry. 24: Wang, Y., Kirpich, I., Liu, Y., Ma, Z., Barve, S., McClain, C. J. and Feng, W Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury. The American Journal of Pathology 179: Younts-Dahl, S. M., Osborn, G. D., Galyean, M. L., Rivera, J. D., Loneragan, G. H. and Brashears, M. M Reduction of Escherichia coli O157 in finishing beef cattle by various doses of Lactobacillus acidophilus in direct-fed microbials. J. Food Prot. 68: ,,,,,, pp pp (Received: 29 November 2013 / Accepted: 2 March 2014)

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경락경혈학회지 Vol.27, No.1, pp.87 106, 2010 Journal of Meridian & Acupoint Dept. of 1 Meridian & Acupoint, 3 Acupuncture & Moxibustion, College of Oriental Medicine, Daejeon University 2 Division of Clinical