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Microbiome and Diseases: Hepatic Disorders

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The Gut Microbiome in Health and Disease

Abstract

Intensive research efforts aim to understand the multifaceted molecular mechanisms underlying disease onset and progression of nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease (ALD). Taken together, NAFLD and ALD are the most common liver diseases worldwide, and universally accepted therapies other than lifestyle interventions either focusing on weight reduction and physical exercise or alcohol abstinence are lacking. During the last decade, alterations of intestinal microbiota composition and intestinal barrier function leading to an increased translocation of bacterial endotoxin and of metabolites originating from an altered intestinal microbiome are emerging as key pathogenic factors in both diseases. In this book chapter, present knowledge and understanding of the interplay of intestinal microbiota, intestinal barrier function, and the development of nonalcoholic and alcoholic liver diseases, respectively, are summarized.

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References

  • Adachi, Y., Bradford, B. U., Gao, W., Bojes, H. K., & Thurman, R. G. (1994). Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology, 20, 453–460.

    Article  PubMed  CAS  Google Scholar 

  • Adachi, Y., Moore, L. E., Bradford, B. U., Gao, W., & Thurman, R. G. (1995). Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology, 108, 218–224.

    Article  PubMed  CAS  Google Scholar 

  • Backhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., et al. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America, 101, 15718–15723.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bajaj, J. S., Heuman, D. M., Sanyal, A. J., Hylemon, P. B., Sterling, R. K., Stravitz, R. T., et al. (2013). Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy. PLoS One, 8, e60042.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bajaj, J. S., Heuman, D. M., Hylemon, P. B., Sanyal, A. J., White, M. B., Monteith, P., et al. (2014). Altered profile of human gut microbiome is associated with cirrhosis and its complications. Journal of Hepatology, 60, 940–947.

    Article  PubMed  CAS  Google Scholar 

  • Bala, S., Marcos, M., Gattu, A., Catalano, D., & Szabo, G. (2014). Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals. PLoS One, 9, e96864.

    Article  PubMed  PubMed Central  Google Scholar 

  • Balmer, M. L., Slack, E., de Gottardi, A., Lawson, M. A., Hapfelmeier, S., Miele, L., et al. (2014). The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Science Translational Medicine, 6, 237ra266.

    Article  CAS  Google Scholar 

  • Barrea, L., Di Somma, C., Muscogiuri, G., Tarantino, G., Tenore, G. C., Orio, F., et al. (2017). Nutrition, inflammation and liver-spleen axis. Critical Reviews in Food Science and Nutrition, 57(16), 3472–3488.

    Article  CAS  Google Scholar 

  • Beilharz, J. E., Kaakoush, N. O., Maniam, J., & Morris, M. J. (2016). The effect of short-term exposure to energy-matched diets enriched in fat or sugar on memory, gut microbiota and markers of brain inflammation and plasticity. Brain, Behavior, and Immunity, 57, 304–313.

    Article  PubMed  Google Scholar 

  • Bergheim, I., Weber, S., Vos, M., Kramer, S., Volynets, V., Kaserouni, S., et al. (2008). Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. Journal of Hepatology, 48, 983–992.

    Article  PubMed  CAS  Google Scholar 

  • Bode, J. C., Bode, C., Heidelbach, R., Durr, H. K., & Martini, G. A. (1984). Jejunal microflora in patients with chronic alcohol abuse. Hepato-Gastroenterology, 31, 30–34.

    PubMed  CAS  Google Scholar 

  • Bode, C., Kugler, V., & Bode, J. C. (1987). Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. Journal of Hepatology, 4, 8–14.

    Article  PubMed  CAS  Google Scholar 

  • Bode, C., Kolepke, R., Schafer, K., & Bode, J. C. (1993). Breath hydrogen excretion in patients with alcoholic liver disease – evidence of small intestinal bacterial overgrowth. Zeitschrift für Gastroenterologie, 31, 3–7.

    PubMed  CAS  Google Scholar 

  • Boursier, J., Mueller, O., Barret, M., Machado, M., Fizanne, L., Araujo-Perez, F., et al. (2016). The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology, 63, 764–775.

    Article  PubMed  CAS  Google Scholar 

  • Brun, P., Castagliuolo, I., Di Leo, V., Buda, A., Pinzani, M., Palu, G., et al. (2007). Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. American Journal of Physiology. Gastrointestinal and Liver Physiology, 292, G518–G525.

    Article  PubMed  CAS  Google Scholar 

  • Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., et al. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes, 57, 1470–1481.

    Article  PubMed  CAS  Google Scholar 

  • Casafont Morencos, F., de las Heras Castano, G., Martin Ramos, L., Lopez Arias, M. J., Ledesma, F., & Pons Romero, F. (1996). Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Digestive Diseases and Sciences, 41, 552–556.

    Article  PubMed  CAS  Google Scholar 

  • Chen, Y., Qin, N., Guo, J., Qian, G., Fang, D., Shi, D., et al. (2014). Functional gene arrays-based analysis of fecal microbiomes in patients with liver cirrhosis. BMC Genomics, 15, 753.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen, L. Z., Xin, Y. N., Geng, N., Jiang, M., Zhang, D. D., & Xuan, S. Y. (2015). PNPLA3 I148M variant in nonalcoholic fatty liver disease: demographic and ethnic characteristics and the role of the variant in nonalcoholic fatty liver fibrosis. World Journal of Gastroenterology, 21, 794–802.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., et al. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505, 559–563.

    Article  PubMed  CAS  Google Scholar 

  • Del Chierico, F., Nobili, V., Vernocchi, P., Russo, A., Stefanis, C., Gnani, D., et al. (2017). Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology, 65, 451–464.

    Article  PubMed  CAS  Google Scholar 

  • Dukowicz, A. C., Lacy, B. E., & Levine, G. M. (2007). Small intestinal bacterial overgrowth: A comprehensive review. Gastroenterology and Hepatology (New York), 3, 112–122.

    Google Scholar 

  • Dulai, P. S., Singh, S., Patel, J., Soni, M., Prokop, L. J., Younossi, Z., et al. (2017). Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology, 65, 1557–1565.

    Article  PubMed  CAS  Google Scholar 

  • Elamin, E. E., Masclee, A. A., Dekker, J., & Jonkers, D. M. (2013). Ethanol metabolism and its effects on the intestinal epithelial barrier. Nutrition Reviews, 71, 483–499.

    Article  PubMed  Google Scholar 

  • Engstler, A. J., Aumiller, T., Degen, C., Durr, M., Weiss, E., Maier, I. B., et al. (2016). Insulin resistance alters hepatic ethanol metabolism: Studies in mice and children with non-alcoholic fatty liver disease. Gut, 65, 1564–1571.

    Article  PubMed  CAS  Google Scholar 

  • Engstler, A. J., Sellmann, C., Jin, C. J., Brandt, A., Herz, K., Priebs, J., et al. (2017). Treatment with alpha-galactosylceramide protects mice from early onset of nonalcoholic steatohepatitis: Role of intestinal barrier function. Molecular Nutrition and Food Research, 61(5). https://doi.org/10.1002/mnfr.201600985

  • Enomoto, N., Ikejima, K., Yamashina, S., Hirose, M., Shimizu, H., Kitamura, T., et al. (2001). Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin. Alcoholism: Clinical and Experimental Research, 25, 51S–54S.

    Article  CAS  Google Scholar 

  • Fu, X. S., & Jiang, F. (2006). Cisapride decreasing orocecal transit time in patients with nonalcoholic steatohepatitis. Hepatobiliary and Pancreatic Diseases International: HBPD INT, 5, 534–537.

    PubMed  CAS  Google Scholar 

  • Fukui, H., Brauner, B., Bode, J. C., & Bode, C. (1991). Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. Journal of Hepatology, 12, 162–169.

    Article  PubMed  CAS  Google Scholar 

  • Gaeta, G. B., Perna, P., Adinolfi, L. E., Utili, R., & Ruggiero, G. (1982). Endotoxemia in a series of 104 patients with chronic liver diseases: Prevalence and significance. Digestion, 23, 239–244.

    Article  PubMed  CAS  Google Scholar 

  • Gangarapu, V., Ince, A. T., Baysal, B., Kayar, Y., Kilic, U., Gok, O., et al. (2015). Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. European Journal of Gastroenterology and Hepatology, 27, 840–845.

    Article  PubMed  CAS  Google Scholar 

  • Grander, C., Adolph, T. E., Wieser, V., Lowe, P., Wrzosek, L., Gyongyosi, B., et al. (2018). Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut, 67(5), 891–901. https://doi.org/10.1136/gutjnl-2016-313432

    Article  PubMed  Google Scholar 

  • György, P. (1954). Antibiotics and liver injury. Annals of the New York Academy of Sciences, 57, 925–931.

    Article  PubMed  Google Scholar 

  • Hagstrom, H. (2017). Alcohol consumption in concomitant liver disease: How much is too much? Current Hepatology Reports, 16, 152–157.

    Article  PubMed  PubMed Central  Google Scholar 

  • Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., et al. (2012). Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature, 482, 179–185.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hirakawa, M., Iida, M., Kohrogi, N., & Fujishima, M. (1988). Hydrogen breath test assessment of orocecal transit time: comparison with barium meal study. The American Journal of Gastroenterology, 83, 1361–1363.

    PubMed  CAS  Google Scholar 

  • Jena, P. K., Prajapati, B., Mishra, P. K., & Seshadri, S. (2016). Influence of gut microbiota on inflammation and pathogenesis of sugar rich diet induced diabetes. Immunome Research, 12(1), 109.

    Google Scholar 

  • Jiang, W., Wu, N., Wang, X., Chi, Y., Zhang, Y., Qiu, X., et al. (2015). Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Scientific Reports, 5, 8096.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jin, C. J., Engstler, A. J., Sellmann, C., Ziegenhardt, D., Landmann, M., Kanuri, G., et al. (2016). Sodium butyrate protects mice from the development of the early signs of nonalcoholic fatty liver disease: Role of melatonin and lipid peroxidation. The British Journal of Nutrition, 23, 1–12.

    Google Scholar 

  • Jin, C. J., Engstler, A. J., Ziegenhardt, D., Bischoff, S. C., Trautwein, C., & Bergheim, I. (2017). Loss of lipopolysaccharide-binding protein attenuates the development of diet-induced non-alcoholic fatty liver disease in mice. Journal of Gastroenterology and Hepatology, 32, 708–715.

    Article  PubMed  CAS  Google Scholar 

  • Jun, D. W., Kim, K. T., Lee, O. Y., Chae, J. D., Son, B. K., Kim, S. H., et al. (2010). Association between small intestinal bacterial overgrowth and peripheral bacterial DNA in cirrhotic patients. Digestive Diseases and Sciences, 55, 1465–1471.

    Article  PubMed  CAS  Google Scholar 

  • Kanuri, G., Spruss, A., Wagnerberger, S., Bischoff, S. C., & Bergheim, I. (2011). Role of tumor necrosis factor α (TNFα) in the onset of fructose-induced nonalcoholic fatty liver disease in mice. The Journal of Nutritional Biochemistry, 22, 527–534.

    Article  PubMed  CAS  Google Scholar 

  • Kanuri, G., Ladurner, R., Skibovskaya, J., Spruss, A., Konigsrainer, A., Bischoff, S. C., et al. (2015). Expression of toll-like receptors 1-5 but not TLR 6-10 is elevated in livers of patients with non-alcoholic fatty liver disease. Liver International, 35, 562–568.

    Article  PubMed  CAS  Google Scholar 

  • Kim, C. H., & Younossi, Z. M. (2008). Nonalcoholic fatty liver disease: A manifestation of the metabolic syndrome. Cleveland Clinic Journal of Medicine, 75, 721–728.

    Article  PubMed  Google Scholar 

  • Kirpich, I. A., Feng, W., Wang, Y., Liu, Y., Beier, J. I., Arteel, G. E., et al. (2013). Ethanol and dietary unsaturated fat (corn oil/linoleic acid enriched) cause intestinal inflammation and impaired intestinal barrier defense in mice chronically fed alcohol. Alcohol (Fayetteville, New York), 47, 257–264.

    Article  CAS  Google Scholar 

  • Koop, D. R., Klopfenstein, B., Iimuro, Y., & Thurman, R. G. (1997). Gadolinium chloride blocks alcohol-dependent liver toxicity in rats treated chronically with intragastric alcohol despite the induction of CYP2E1. Molecular Pharmacology, 51, 944–950.

    Article  PubMed  CAS  Google Scholar 

  • Lakshmi, C. P., Ghoshal, U. C., Kumar, S., Goel, A., Misra, A., Mohindra, S., et al. (2010). Frequency and factors associated with small intestinal bacterial overgrowth in patients with cirrhosis of the liver and extra hepatic portal venous obstruction. Digestive Diseases and Sciences, 55, 1142–1148.

    Article  PubMed  CAS  Google Scholar 

  • Lam, Y. Y., Ha, C. W., Hoffmann, J., Oscarsson, J., Dinudom, A., Mather, T. J., et al. (2015). Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice. Obesity, 23, 1429–1439.

    Article  PubMed  CAS  Google Scholar 

  • Leclercq, S., De Saeger, C., Delzenne, N., de Timary, P., & Stärkel, P. (2014a). Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence. Biological Psychiatry, 76, 725–733.

    Article  PubMed  CAS  Google Scholar 

  • Leclercq, S., Matamoros, S., Cani, P. D., Neyrinck, A. M., Jamar, F., Stärkel, P., et al. (2014b). Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proceedings of the National Academy of Sciences of the United States of America, 111, E4485–E4493.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ley, R. E., Backhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., & Gordon, J. I. (2005). Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America, 102, 11070–11075.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lin, R.-S., Lee, F.-Y., Lee, S.-D., Tsai, Y.-T., Lin, H. C., Rei-Hwa, L., et al. (1995). Endotoxemia in patients with chronic liver diseases: Relationship to severity of liver diseases, presence of esophaegeal varices, and hyperdynamic circulation. Journal of Hepatology, 22, 165–172.

    Article  PubMed  CAS  Google Scholar 

  • Loomba, R., Seguritan, V., Li, W., Long, T., Klitgord, N., Bhatt, A., et al. (2017). Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metabology, 25, 1054–1062 e1055.

    Article  CAS  Google Scholar 

  • Luckey, T., Reyniers, J., György, P., & Forbes, M. (1954). Germfree animals and liver necrosis. Annals of the New York Academy of Sciences, 57, 932–935.

    Article  PubMed  CAS  Google Scholar 

  • Ludwig, J., Viggiano, T. R., McGill, D. B., & Oh, B. J. (1980). Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clinic Proceedings, 55, 434–438.

    PubMed  CAS  Google Scholar 

  • Mann, R. E., Smart, R. G., & Govoni, R. (2003). The epidemiology of alcoholic liver disease. Alcohol Research and Health, 27, 209–219.

    PubMed  PubMed Central  Google Scholar 

  • Miele, L., Valenza, V., La Torre, G., Montalto, M., Cammarota, G., Ricci, R., et al. (2009). Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology, 49, 1877–1887.

    Article  PubMed  CAS  Google Scholar 

  • Miyaaki, H., & Nakao, K. (2017). Significance of genetic polymorphisms in patients with nonalcoholic fatty liver disease. Clinical Journal of Gastroenterology, 10, 201–207.

    Article  PubMed  Google Scholar 

  • Morencos, F. C., de las Heras Castano, G., Martin Ramos, L., Lopez Arias, M. J., Ledesma, F., & Pons Romero, F. (1995). Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Digestive Diseases and Sciences, 40, 1252–1256.

    Article  PubMed  CAS  Google Scholar 

  • Muegge, B. D., Kuczynski, J., Knights, D., Clemente, J. C., González, A., Fontana, L., et al. (2011). Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science (New York), 332, 970–974.

    Article  CAS  Google Scholar 

  • Mutlu, E. A., Gillevet, P. M., Rangwala, H., Sikaroodi, M., Naqvi, A., Engen, P. A., et al. (2012). Colonic microbiome is altered in alcoholism. American Journal of Physiology – Gastrointestinal and Liver Physiology, 302, G966–G978.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nazim, M., Stamp, G., & Hodgson, H. J. (1989). Non-alcoholic steatohepatitis associated with small intestinal diverticulosis and bacterial overgrowth. Hepato-Gastroenterology, 36, 349–351.

    PubMed  CAS  Google Scholar 

  • Neuschwander-Tetri, B. A., & Caldwell, S. H. (2003). Nonalcoholic steatohepatitis: Summary of an AASLD single topic conference. Hepatology, 37, 1202–1219.

    Article  PubMed  Google Scholar 

  • Pande, C., Kumar, A., & Sarin, S. K. (2009). Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease. Alimentary Pharmacology and Therapeutics, 29, 1273–1281.

    Article  PubMed  CAS  Google Scholar 

  • Parlesak, A., Schafer, C., Schutz, T., Bode, J. C., & Bode, C. (2000). Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. Journal of Hepatology, 32, 742–747.

    Article  PubMed  CAS  Google Scholar 

  • Pataky, Z., Genton, L., Spahr, L., Lazarevic, V., Terraz, S., Gaia, N., et al. (2016). Impact of hypocaloric hyperproteic diet on gut microbiota in overweight or obese patients with nonalcoholic fatty liver disease: A pilot study. Digestive Diseases and Sciences, 61, 2721–2731.

    Article  PubMed  CAS  Google Scholar 

  • Patterson, E., O’Doherty, R. M., Murphy, E. F., Wall, R., O’Sullivan, O., Nilaweera, K., et al. (2014). Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice. British Journal of Nutrition, 111, 1905–1917.

    Article  CAS  Google Scholar 

  • Rehm, J., Taylor, B., Mohapatra, S., Irving, H., Baliunas, D., Patra, J., et al. (2010). Alcohol as a risk factor for liver cirrhosis: A systematic review and meta-analysis. Drug and Alcohol Review, 29, 437–445.

    Article  PubMed  Google Scholar 

  • Rivera, C. A., Bradford, B. U., Seabra, V., & Thurman, R. G. (1998). Role of endotoxin in the hypermetabolic state after acute ethanol exposure. The American Journal of Physiology, 275, G1252–G1258.

    PubMed  CAS  Google Scholar 

  • Romero-Gomez, M., Zelber-Sagi, S., & Trenell, M. (2017). Treatment of NAFLD with diet, physical activity and exercise. Journal of Hepatology, 67(4), 829–846.

    Article  PubMed  Google Scholar 

  • Ruiz, A. G., Casafont, F., Crespo, J., Cayón, A., Mayorga, M., Estebanez, A., et al. (2007). Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: Evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obesity Surgery, 17, 1374.

    Article  PubMed  Google Scholar 

  • Rutenburg, A. M., Sonnenblick, E., Koven, I., Aprahamian, H. A., Reiner, L., & Fine, J. (1957). The role of intestinal bacteria in the development of dietary cirrhosis in rats. The Journal of Experimental Medicine, 106, 1–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Satapathy, S. K., & Sanyal, A. J. (2015). Epidemiology and natural history of nonalcoholic fatty liver disease. Seminars in Liver Disease, 35, 221–235.

    Article  PubMed  Google Scholar 

  • Savolainen, V., Liesto, K., Männikkö, A., Penttilä, A., & Karhunen, P. (1993). Alcohol consumption and alcoholic liver disease: evidence of a threshold level of effects of ethanol. Alcoholism: Clinical and Experimental Research, 17, 1112–1117.

    Article  CAS  Google Scholar 

  • Schuppan, D., & Schattenberg, J. M. (2013). Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. Journal of Gastroenterology and Hepatology, 28(Suppl 1), 68–76.

    Article  PubMed  CAS  Google Scholar 

  • Sellmann, C., Priebs, J., Landmann, M., Degen, C., Engstler, A. J., Jin, C. J., et al. (2015). Diets rich in fructose, fat or fructose and fat alter intestinal barrier function and lead to the development of nonalcoholic fatty liver disease over time. The Journal of Nutritional Biochemistry, 26, 1183–1192.

    Article  PubMed  CAS  Google Scholar 

  • Shapiro, H., Suez, J., & Elinav, E. (2017). Personalized microbiome-based approaches to metabolic syndrome management and prevention. Journal of Diabetes, 9, 226–236.

    Article  PubMed  Google Scholar 

  • Sonnenburg, J. L., & Backhed, F. (2016). Diet-microbiota interactions as moderators of human metabolism. Nature, 535, 56–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Soza, A., Riquelme, A., Gonzalez, R., Alvarez, M., Perez-Ayuso, R. M., Glasinovic, J. C., et al. (2005). Increased orocecal transit time in patients with nonalcoholic fatty liver disease. Digestive Diseases and Sciences, 50, 1136–1140.

    Article  PubMed  Google Scholar 

  • Spencer, M. D., Hamp, T. J., Reid, R. W., Fischer, L. M., Zeisel, S. H., & Fodor, A. A. (2011). Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology, 140, 976–986.

    Article  PubMed  CAS  Google Scholar 

  • Spruss, A., Kanuri, G., Wagnerberger, S., Haub, S., Bischoff, S. C., & Bergheim, I. (2009). Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology, 50, 1094–1104.

    Article  PubMed  CAS  Google Scholar 

  • Spruss, A., Kanuri, G., Uebel, K., Bischoff, S. C., & Bergheim, I. (2011). Role of the inducible nitric oxide synthase in the onset of fructose-induced steatosis in mice. Antioxidants and Redox Signaling, 14, 2121–2135.

    Article  PubMed  CAS  Google Scholar 

  • Spruss, A., Kanuri, G., Stahl, C., Bischoff, S. C., & Bergheim, I. (2012). Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function. Laboratory Investigation, 92, 1020–1032.

    Article  PubMed  CAS  Google Scholar 

  • Starkel, P., & Schnabl, B. (2016). Bidirectional communication between liver and gut during alcoholic liver disease. Seminars in Liver Disease, 36, 331–339.

    Article  PubMed  CAS  Google Scholar 

  • Starley, B. Q., Calcagno, C. J., & Harrison, S. A. (2010). Nonalcoholic fatty liver disease and hepatocellular carcinoma: A weighty connection. Hepatology, 51, 1820–1832.

    Article  PubMed  Google Scholar 

  • Sutter, A. G., Palanisamy, A. P., Lench, J. H., Jessmore, A. P., & Chavin, K. D. (2015). Development of steatohepatitis in Ob/Ob mice is dependent on Toll-like receptor 4. Annals of Hepatology, 14, 735–743.

    PubMed  CAS  Google Scholar 

  • Szabo, G. (2015). Gut-liver axis in alcoholic liver disease. Gastroenterology, 148, 30–36.

    Article  PubMed  CAS  Google Scholar 

  • Thuy, S., Ladurner, R., Volynets, V., Wagner, S., Strahl, S., Konigsrainer, A., et al. (2008). Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. The Journal of Nutrition, 138, 1452–1455.

    Article  PubMed  CAS  Google Scholar 

  • Townsend, S. A., & Newsome, P. N. (2016). Non-alcoholic fatty liver disease in 2016. British Medical Bulletin, 119, 143–156.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Uesugi, T., Froh, M., Arteel, G. E., Bradford, B. U., & Thurman, R. G. (2001). Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology, 34, 101–108.

    Article  PubMed  CAS  Google Scholar 

  • Volynets, V., Kuper, M. A., Strahl, S., Maier, I. B., Spruss, A., Wagnerberger, S., et al. (2012). Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease (NAFLD). Digestive Diseases and Sciences, 57, 1932–1941.

    Article  PubMed  CAS  Google Scholar 

  • Vrieze, A., Van Nood, E., Holleman, F., Salojarvi, J., Kootte, R. S., Bartelsman, J. F., et al. (2012). Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, 143, 913–916 e917.

    Article  PubMed  CAS  Google Scholar 

  • Wagnerberger, S., Spruss, A., Kanuri, G., Volynets, V., Stahl, C., Bischoff, S. C., et al. (2012). Toll-like receptors 1-9 are elevated in livers with fructose-induced hepatic steatosis. The British Journal of Nutrition, 107, 1727–1738.

    Article  PubMed  CAS  Google Scholar 

  • Wagnerberger, S., Fiederlein, L., Kanuri, G., Stahl, C., Millonig, G., Mueller, S., et al. (2013). Sex-specific differences in the development of acute alcohol-induced liver steatosis in mice. Alcohol and Alcoholism (Oxford, Oxfordshire), 48, 648–656.

    Article  CAS  Google Scholar 

  • Wiest, R., Albillos, A., Trauner, M., Bajaj, J. S., & Jalan, R. (2017). Targeting the gut-liver axis in liver disease. Journal of Hepatology, 67(5), 1084–1103.

    Article  PubMed  CAS  Google Scholar 

  • Wigg, A., Roberts-Thomson, I., Dymock, R., McCarthy, P., Grose, R., & Cummins, A. (2001). The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor α in the pathogenesis of non-alcoholic steatohepatitis. Gut, 48, 206–211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • World Health Organization. (2014). Age-standardized death rates of liver cirrhosis. World Health Organization.

    Google Scholar 

  • World Health Organization, and Unit, W.H.O.M.o.S.A. (2014). Global status report on alcohol and health, 2014. World Health Organization.

    Google Scholar 

  • Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y. Y., Keilbaugh, S. A., et al. (2011). Linking long-term dietary patterns with gut microbial enterotypes. Science, 334, 105–108.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu, H., Esteve, E., Tremaroli, V., Khan, M. T., Caesar, R., Manneras-Holm, L., et al. (2017). Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nature Medicine, 23, 850–858.

    Article  PubMed  CAS  Google Scholar 

  • Yang, C. Y., Chang, C. S., & Chen, G. H. (1998). Small-intestinal bacterial overgrowth in patients with liver cirrhosis, diagnosed with glucose H2 or CH4 breath tests. Scandinavian Journal of Gastroenterology, 33, 867–871.

    Article  PubMed  CAS  Google Scholar 

  • Yeh, M. M., & Brunt, E. M. (2014). Pathological features of fatty liver disease. Gastroenterology, 147, 754–764.

    Article  PubMed  CAS  Google Scholar 

  • Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016). Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1), 73–84. https://doi.org/10.1002/hep.28431

    Article  PubMed  Google Scholar 

  • Yuki, T., & Thurman, R. G. (1980). The swift increase in alcohol metabolism. Time course for the increase in hepatic oxygen uptake and the involvement of glycolysis. Biochemical Journal, 186, 119–126.

    Article  PubMed Central  CAS  Google Scholar 

  • Zhu, Y., Lin, X., Zhao, F., Shi, X., Li, H., Li, Y., et al. (2015). Meat, dairy and plant proteins alter bacterial composition of rat gut bacteria. Scientific Reports, 5, 15220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu, Y., Shi, X., Lin, X., Ye, K., Xu, X., Li, C., et al. (2017). Beef, chicken, and soy proteins in diets induce different gut microbiota and metabolites in rats. Frontiers in Microbiology, 8, 1395.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zmora, N., Zeevi, D., Korem, T., Segal, E., & Elinav, E. (2016). Taking it personally: Personalized utilization of the human microbiome in health and disease. Cell Host and Microbe, 19, 12–20.

    Article  PubMed  CAS  Google Scholar 

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Bergheim, I., Schuppan, D. (2018). Microbiome and Diseases: Hepatic Disorders. In: Haller, D. (eds) The Gut Microbiome in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-90545-7_17

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