Skip to main content
SpringerLink
Log in

Metagenomic Applications and the Potential for Understanding Chronic Liver Disease

  • Chapter
  • First Online:
Metagenomics of the Human Body

  • 1786 Accesses

Abstract

Liver fibrosis is characterized by an excessive deposition of extracellular matrix proteins that occurs in chronic liver disease of any origin. Cirrhosis occurs with the development of regenerating nodules of hepatocytes. Patients with decompensated liver cirrhosis have a poor prognosis, and liver transplantation is often necessary. There are no effective antifibrotic treatments for patients with chronic liver diseases. Intestinal dysbiosis and bacterial translocation are common in patients with liver disease, and there is strong evidence that the translocation of bacteria and their products across the epithelial barrier contributes to the progression of liver fibrosis. Supporting evidence comes from animal studies demonstrating that intestinal decontamination is associated with decreased liver fibrogenesis. Despite this strong association, the exact molecular mechanism of how intestinal bacterial overgrowth and translocation contribute to liver disease progression remains unknown. In this chapter we describe microbial changes in response to liver injury and chronic liver disease and the consequences of intestinal dysbiosis on host biology. We will initially focus on fatty liver disease associated with obesity and liver injury induced by alcohol. We then highlight how therapeutic interventions may modify the gastrointestinal microflora and prevent or reduce disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG (1995) Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology 108:218–224

    Article  CAS  PubMed  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  CAS  PubMed  Google Scholar 

  • Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101:15718–15723

    Article  PubMed Central  PubMed  Google Scholar 

  • Backhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104:979–984

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115:209–218

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bauer TM, Fernandez J, Navasa M, Vila J, Rodes J (2002) Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis. J Hepatol 36:501–506

    Article  PubMed  Google Scholar 

  • Bauer TM, Schwacha H, Steinbruckner B, Brinkmann FE, Ditzen AK, Aponte JJ, Pelz K, Berger D, Kist M, Blum HE (2002) Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia. Am J Gastroenterol 97:2364–2370

    Article  PubMed  Google Scholar 

  • Bauer TM, Steinbruckner B, Brinkmann FE, Ditzen AK, Schwacha H, Aponte JJ, Pelz K, Kist M, Blum HE (2001) Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. Am J Gastroenterol 96:2962–2967

    Article  CAS  PubMed  Google Scholar 

  • Bode C, Bode JC (2005) Activation of the innate immune system and alcoholic liver disease: effects of ethanol per se or enhanced intestinal translocation of bacterial toxins induced by ethanol? Alcohol Clin Exp Res 29:166S–171S

    Article  CAS  PubMed  Google Scholar 

  • Bode C, Kugler V, Bode JC (1987) Endotoxemia in patients with alcoholic and nonalcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol 4:8–14

    Article  CAS  PubMed  Google Scholar 

  • Bode JC, Bode C, Heidelbach R, Durr HK, Martini GA (1984) Jejunal microflora in patients with chronic alcohol abuse. Hepatogastroenterology 31:30–34

    CAS  PubMed  Google Scholar 

  • Brandl K, Plitas G, Mihu CN, Ubeda C, Jia T, Fleisher M, Schnabl B, DeMatteo RP, Pamer EG (2008) Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455:804–807

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Camp JG, Kanther M, Semova I, Rawls JF (2009) Patterns and scales in gastrointestinal microbial ecology. Gastroenterology 136:1989–2002

    Article  PubMed  Google Scholar 

  • Casafont Morencos F, de las Heras Castano G, Martin Ramos L, Lopez Arias MJ, Ledesma F, Pons Romero F (1996) Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Dig Dis Sci 41:552–556

    Article  CAS  PubMed  Google Scholar 

  • Chang CS, Chen GH, Lien HC, Yeh HZ (1998) Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology 28:1187–1190

    Article  CAS  PubMed  Google Scholar 

  • Chiva M, Guarner C, Peralta C, Llovet T, Gomez G, Soriano G, Balanzo J (2003) Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats. Eur J Gastroenterol Hepatol 15:145–150

    Article  PubMed  Google Scholar 

  • Chiva M, Soriano G, Rochat I, Peralta C, Rochat F, Llovet T, Mirelis B, Schiffrin EJ, Guarner C, Balanzo J (2002) Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis. J Hepatol 37:456–462

    Article  CAS  PubMed  Google Scholar 

  • Cirera I, Bauer TM, Navasa M, Vila J, Grande L, Taura P, Fuster J, Garcia-Valdecasas JC, Lacy A, Suarez MJ, Rimola A, Rodes J (2001) Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 34:32–37

    Article  CAS  PubMed  Google Scholar 

  • Ding JW, Andersson R, Soltesz V, Willen R, Bengmark S (1994) Obstructive jaundice impairs reticuloendothelial function and promotes bacterial translocation in the rat. J Surg Res 57:238–245

    Article  CAS  PubMed  Google Scholar 

  • Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside J, Tatoud R, Blanc V, Lindon JC, Mitchell SC, Holmes E, McCarthy MI, Scott J, Gauguier D, Nicholson JK (2006) Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci USA 103:12511–12516

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308:1635–1638

    Article  PubMed Central  PubMed  Google Scholar 

  • Enomoto N, Ikejima K, Yamashina S, Hirose M, Shimizu H, Kitamura T, Takei Y, Sato, Thurman RG (2001) Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin. Alcohol Clin Exp Res 25:51S–54S

    Article  CAS  PubMed  Google Scholar 

  • Enomoto N, Yamashina S, Kono H, Schemmer P, Rivera CA, Enomoto A, Nishiura T, Nishimura T, Brenner DA, Thurman RG (1999) Development of a new, simple rat model of early alcohol-induced liver injury based on sensitization of Kupffer cells. Hepatology 29:1680–1689

    Article  CAS  PubMed  Google Scholar 

  • Ferrier L, Berard F, Debrauwer L, Chabo C, Langella P, Bueno L, Fioramonti J (2006) Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents. Am J Pathol 168:1148–1154

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fleming S, Toratani S, Shea-Donohue T, Kashiwabara Y, Vogel SN, Metcalf ES (2001) Pro- and anti-inflammatory gene expression in the murine small intestine and liver after chronic exposure to alcohol. Alcohol Clin Exp Res 25:579–589

    Article  CAS  PubMed  Google Scholar 

  • Frances R, Chiva M, Sanchez E, Gonzalez-Navajas JM, Llovet T, Zapater P, Soriano G, Munoz C, Balanzo J, Perez-Mateo M, Song XY, Guarner C, Such J (2007) Bacterial translocation is downregulated by anti-TNF-alpha monoclonal antibody administration in rats with cirrhosis and ascites. J Hepatol 46:797–803

    Article  CAS  PubMed  Google Scholar 

  • Frances R, Zapater P, Gonzalez-Navajas JM, Munoz C, Cano R, Moreu R, Pascual S, Bellot P, Perez-Mateo M, Such J (2008) Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis. Hepatology 47:978–985

    Article  CAS  PubMed  Google Scholar 

  • Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular–phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104:13780–13785

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Gabele E, Muhlbauer M, Dorn C, Weiss TS, Froh M, Schnabl B, Wiest R, Scholmerich J, Obermeier F, Hellerbrand C (2008) Role of TLR9 in hepatic stellate cells and experimental liver fibrosis. Biochem Biophys Res Commun 376:271–276

    Article  PubMed  Google Scholar 

  • Garcia-Tsao G, Lee FY, Barden GE, Cartun R, West AB (1995) Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites. Gastroenterology 108:1835–1841

    Article  CAS  PubMed  Google Scholar 

  • Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131:33–45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Genesca J, Marti R, Rojo F, Campos F, Peribanez V, Gonzalez A, Castells L, Ruiz-Marcellan C, Margarit C, Esteban R, Guardia J, Segura R (2003) Increased tumour necrosis factor alpha production in mesenteric lymph nodes of cirrhotic patients with ascites. Gut 52:1054–1059

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gines P, Cardenas A, Arroyo V, Rodes J (2004) Management of cirrhosis and ascites. N Engl J Med 350:1646–1654

    Article  CAS  PubMed  Google Scholar 

  • Guarner C, Gonzalez-Navajas JM, Sanchez E, Soriando G, Frances R, Chiva M, Zapater P, Benlloch S, Munoz C, Pascual S, Balanzo J, Perez-Mateo M, Such J (2006) The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation. Hepatology 44:633–639

    Article  CAS  PubMed  Google Scholar 

  • Guarner C, Runyon BA, Young S, Heck M, Sheikh MY (1997) Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites. J Hepatol 26:1372–1378

    Article  CAS  PubMed  Google Scholar 

  • Gunnarsdottir SA, Sadik R, Shev S, Simren M, Sjovall H, Stotzer PO, Abrahamsson H, Olsson R, Bjornsson ES (2003) Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension. Am J Gastroenterol 98:1362–1370

    Article  PubMed  Google Scholar 

  • Guo J, Loke J, Zheng F, Hong F, Yea S, Fukata M, Tarocchi M, Abar OT, Huang H, Sninsky JJ, Friedman SL (2009) Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses. Hepatology 49:960–968

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, Rowland CM, Catanese JJ, Leong DU, Sninsky JJ, Layden TJ, Wright TL, White T, Cheung RC (2007) A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology 46:297–306

    Article  CAS  PubMed  Google Scholar 

  • Inagaki T, Moschetta A, Lee YK, Peng L, Zhao G, Downes M, Yu RT, Shelton JM, Richardson JA, Repa JJ, Mangelsdorf DJ, Kliewer SA (2006) Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci USA 103:3920–3925

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Inamura T, Miura S, Tsuzuki Y, Hara Y, Hokari R, Ogawa T, Teramoto K, Watanabe C, Kobayashi H, Nagata H, Ishii H (2003) Alteration of intestinal intraepithelial lymphocytes and increased bacterial translocation in a murine model of cirrhosis. Immunol Lett 90:3–11

    Article  CAS  PubMed  Google Scholar 

  • Isayama F, Hines IN, Kremer M, Milton RJ, Byrd CL, Perry AW, McKim SE, Parsons C, Rippe RA, Wheeler MD (2006) LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice. Am J Physiol Gastrointest Liver Physiol 290:G1318-1328

    Google Scholar 

  • Jun DW, Kim KT, Lee OY, Chae JD, Son BK, Kim SH, Jo YJ, Park YS (2009) Association between small intestinal bacterial overgrowth and peripheral bacterial DNA in cirrhotic patients. Dig Dis Sci

    Google Scholar 

  • Keshavarzian A, Farhadi A, Forsyth CB, Rangan J, Jakate S, Shaikh M, Banan A, Fields JZ (2009) Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in rats. J Hepatol 50:538–547

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kirpich IA, Solovieva NV, Leikhter SN, Shidakova NA, Lebedeva OV, Sidorov PI, Bazhukova TA, Soloviev AG, Barve SS, McClain CJ, Cave M (2008) Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol 42:675–682

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lata J, Novotny I, Pribramska V, Jurankova J, Fric P, Kroupa R, Stiburek O (2007) The effect of probiotics on gut flora, level of endotoxin and Child–Pugh score in cirrhotic patients: results of a double-blind randomized study. Eur J Gastroenterol Hepatol 19:1111–1113

    Article  PubMed  Google Scholar 

  • Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, Song XY, Diehl AM (2003) Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 37:343–350

    Article  CAS  PubMed  Google Scholar 

  • Lichtman SN, Sartor RB, Keku J, Schwab JH (1990) Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology 98:414–423

    CAS  PubMed  Google Scholar 

  • Lin RS, Lee FY, Lee SD, Tsai YT, Lin HC, Lu RH, Hsu WC, Huang CC, Wang SS, Lo KJ (1995) Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. J Hepatol 22:165–172

    Article  CAS  PubMed  Google Scholar 

  • Lirussi F, Mastropasqua E, Orando S, Orlando R (2007) Probiotics for non-alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database Syst Rev (1): CD005165

    Google Scholar 

  • Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM (2004) Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 39:1441–1449

    Article  PubMed  Google Scholar 

  • Loguercio C, Federico A, Tuccillo C, Terracciano F, D’Auria MV, De Simone C, Del Vecchio Blanco C (2005) Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol 39:540–543

    Article  PubMed  Google Scholar 

  • Ma X, Hua J, Li Z (2008) Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol 49:821–830

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Madrid AM, Cumsille F, Defilippi C (1997) Altered small bowel motility in patients with liver cirrhosis depends on severity of liver disease. Dig Dis Sci 42:738–742

    Article  CAS  PubMed  Google Scholar 

  • Madrid AM, Hurtado C, Venegas M, Cumsille F, Defilippi C (2001) Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am J Gastroenterol 96:1251–1255

    Article  CAS  PubMed  Google Scholar 

  • Mason CM, Dobard E, Kolls J, Nelson S (1998) Effect of alcohol on bacterial translocation in rats. Alcohol Clin Exp Res 22:1640–1645

    Article  CAS  PubMed  Google Scholar 

  • Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449:819–826

    Article  CAS  PubMed  Google Scholar 

  • Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Masciana R, Forgione A, Gabrieli ML, Perotti G, Vecchio FM, Rapaccini G, Gasbarrini G, Day CP, Grieco A (2009) Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 49:1877–1887

    Article  CAS  PubMed  Google Scholar 

  • Morencos FC, de las Heras Castano G, Martin Ramos L, Lopez Arias MJ, Ledesma F, Pons Romero F (1995) Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Dig Dis Sci 40:1252–1256

    Article  CAS  PubMed  Google Scholar 

  • Munoz L, Albillos A, Nieto M, Reyes E, Lledo L, Monserrat J, Sanz E, de la Hera A, Alvarez-Mon M (2005) Mesenteric Th1 polarization and monocyte TNF-alpha production: first steps to systemic inflammation in rats with cirrhosis. Hepatology 42:411–419

    Article  CAS  PubMed  Google Scholar 

  • Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P (2009) Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp Res 33:1836–1846

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nanji AA, Khettry U, Sadrzadeh SM, Yamanaka T (1993) Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2. Am J Pathol 142:367–373

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nanji AA, Khettry U, Sadrzadeh SM (1994) Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease). Proc Soc Exp Biol Med 205:243–247

    Article  CAS  PubMed  Google Scholar 

  • Napolitano LM, Koruda MJ, Zimmerman K, McCowan K, Chang J, Meyer AA (1995) Chronic ethanol intake and burn injury: evidence for synergistic alteration in gut and immune integrity. J Trauma 38:198–207

    Article  CAS  PubMed  Google Scholar 

  • Natarajan SK, Ramamoorthy P, Thomas S, Basivireddy J, Kang G, Ramachandran A, Pulimood AB, Balasubramanian KA (2006) Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: changes in glycosylation and luminal bacteria. Hepatology 43:837–846

    Article  CAS  PubMed  Google Scholar 

  • Pande C, Kumar A, Sarin SK (2009) Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease. Aliment Pharmacol Ther 29:1273–1281

    Article  CAS  PubMed  Google Scholar 

  • Parks RW, Clements WD, Pope C, Halliday MI, Rowlands BJ, Diamond T (1996) Bacterial translocation and gut microflora in obstructive jaundice. J Anat 189(Pt 3):561–565

    PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Pascual S, Such J, Esteban A, Zapater P, Casellas JA, Aparicio JR, Girona E, Gutierrez A, Carnices F, Palazon JM, Sola-Vera J, Perez-Mateo M (2003) Intestinal permeability is increased in patients with advanced cirrhosis. Hepatogastroenterology 50:1482–1486

    PubMed  Google Scholar 

  • Preidis GA, Versalovic J (2009) Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. Gastroenterology 136:2015–2031

    Article  CAS  PubMed  Google Scholar 

  • Rasaratnam B, Kaye D, Jennings G, Dudley F, Chin-Dusting J (2003) The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial. Ann Intern Med 139:186–193

    Article  PubMed  Google Scholar 

  • Runyon BA, Borzio M, Young S, Squier SU, Guarner C, Runyon MA (1995) Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis. Hepatology 21:1719–1724

    CAS  PubMed  Google Scholar 

  • Runyon BA, Squier S, Borzio M (1994) Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis. J Hepatol 21:792–796

    Article  CAS  PubMed  Google Scholar 

  • Rutenburg AM, Sonnenblick E, Koven I, Aprahamian HA, Reiner L, Fine J (1957) The role of intestinal bacteria in the development of dietary cirrhosis in rats. J Exp Med 106:1–14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sanchez E, Casafont F, Guerra A, de Benito I, Pons-Romero F (2005) Role of intestinal bacterial overgrowth and intestinal motility in bacterial translocation in experimental cirrhosis. Rev Esp Enferm Dig 97:805–814

    CAS  PubMed  Google Scholar 

  • Schenk S, Saberi M, Olefsky JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118:2992–3002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF (2007) TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 13:1324–1332

    Article  CAS  PubMed  Google Scholar 

  • Sheth AA, Garcia-Tsao G (2008) Probiotics and liver disease. J Clin Gastroenterol 42(Suppl 2):S80–84

    Article  PubMed  Google Scholar 

  • Shindo K, Machida M, Miyakawa K, Fukumura M (1993) A syndrome of cirrhosis, achlorhydria, small intestinal bacterial overgrowth, and fat malabsorption. Am J Gastroenterol 88:2084–2091

    CAS  PubMed  Google Scholar 

  • Singh N, Gayowski T, Yu VL, Wagener MM (1995) Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial. Ann Intern Med 122:595–598

    Article  CAS  PubMed  Google Scholar 

  • Stadlbauer V, Mookerjee RP, Hodges S, Wright GA, Davies NA, Jalan R (2008) Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis. J Hepatol 48:945–951

    Article  CAS  PubMed  Google Scholar 

  • Such J, Frances R, Munoz C, Zapater P, Casellas JA, Cifuentes A, Rodriguez-Valera F, Pascual S, Sola-Vera J, Carnicer F, Uceda F, Palazon JM, Perez-Mateo M (2002) Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. Hepatology 36:135–141

    Article  CAS  PubMed  Google Scholar 

  • Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288:E462–468

    Article  CAS  PubMed  Google Scholar 

  • Tabata T, Tani T, Endo Y, Hanasawa K (2002) Bacterial translocation and peptidoglycan translocation by acute ethanol administration. J Gastroenterol 37:726–731

    Article  CAS  PubMed  Google Scholar 

  • Tamai H, Kato S, Horie Y, Ohki E, Yokoyama H, Ishii H (2000) Effect of acute ethanol administration on the intestinal absorption of endotoxin in rats. Alcohol Clin Exp Res 24:390–394

    Article  CAS  PubMed  Google Scholar 

  • Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031

    Article  PubMed  Google Scholar 

  • Uesugi T, Froh M, Arteel GE, Bradford BU, Thurman RG (2001) Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology 34:101–108

    Article  CAS  PubMed  Google Scholar 

  • Velayudham A, Dolganiuc A, Ellis M, Petrasek J, Kodys K, Mandrekar P, Szabo G (2009) VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology 49:989–997

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wiest R, Chen F, Cadelina G, Groszmann RJ, Garcia-Tsao G (2003) Effect of Lactobacillus-fermented diets on bacterial translocation and intestinal flora in experimental prehepatic portal hypertension. Dig Dis Sci 48:1136–1141

    Article  CAS  PubMed  Google Scholar 

  • Wiest R, Garcia-Tsao G (2005) Bacterial translocation (BT) in cirrhosis. Hepatology 41:422–433

    Article  CAS  PubMed  Google Scholar 

  • Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG (2001) The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut 48:206–211

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wong F, Bernardi M, Balk R, Christman B, Moreau R, Garcia-Tsao G, Patch D, Soriano G, Hoefs J, Navasa M (2005) Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut 54:718–725

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yin M, Bradford BU, Wheeler MD, Uesugi T, Froh M, Goyert SM, Thurman RG (2001) Reduced early alcohol-induced liver injury in CD14-deficient mice. J Immunol 166:4737–4742

    Article  CAS  PubMed  Google Scholar 

  • Yin M, Wheeler MD, Kono H, Bradford BU, Gallucci RM, Luster MI, Thurman RG (1999) Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice. Gastroenterology 117:942–952

    Article  CAS  PubMed  Google Scholar 

  • Zareie M, Johnson-Henry K, Jury J, Yang PC, Ngan BY, McKay DM, Soderholm JD, Perdue MH, Sherman PM (2006) Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut 55:1553-1560

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao HY, Wang HJ, Lu Z, Xu SZ (2004) Intestinal microflora in patients with liver cirrhosis. Chin J Dig Dis 5:64–67

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

I thank Dr. David A. Brenner, University of California, San Diego, for critically reading this manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, University of California San Diego, MC0702, 9500 Gilman Drive, La Jolla, CA, 92093, USA

    Bernd Schnabl

Authors
  1. Bernd Schnabl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernd Schnabl .

Editor information

Editors and Affiliations

  1. J. Craig Venter Institute (JCVI), 9704 Medical Center Drive, Rockville, 20850, Maryland, USA

    Karen E. Nelson

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Schnabl, B. (2011). Metagenomic Applications and the Potential for Understanding Chronic Liver Disease. In: Nelson, K. (eds) Metagenomics of the Human Body. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7089-3_13

Download citation

Publish with us

Policies and ethics

Search

Navigation