Cited by 1,038Gut microbiota and healthLiver Disease and TransplantationMicrobial Community Ecology and Physiology

Characterization of fecal microbial communities in patients with liver cirrhosis

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Chen, Yanfei, Yang, Fengling, Lu, Haifeng, Wang, Baohong, Chen, Yunbo, Lei, Dajiang, Wang, Yuezhu, Zhu, Baoli +1 more·2011·Hepatology

Abstract

UNLABELLED: Liver cirrhosis is the pathologic end stage of chronic liver disease. Increasing evidence suggests that gut flora is implicated in the pathogenesis of liver cirrhosis complications. The aim of this study was to characterize the fecal microbial community in patients with liver cirrhosis in comparison with healthy individuals. We recruited 36 patients with liver cirrhosis and 24 healthy controls. The fecal microbial communities was analyzed by way of 454 pyrosequencing of the 16S ribosomal RNA V3 region followed by real-time quantitative polymerase chain reaction. Community-wide changes of fecal microbiota in liver cirrhosis were observed compared with healthy controls. The proportion of phylum Bacteroidetes was significantly reduced (P=0.008), whereas Proteobacteria and Fusobacteria were highly enriched in the cirrhosis group (P=0.001 and 0.002, respectively). Enterobacteriaceae (P=0.001), Veillonellaceae (P=0.046), and Streptococcaceae (P=0.001) were prevalent in patients with cirrhosis at the family level. A positive correlation was observed between Child-Turcotte-Pugh (CTP) score and Streptococcaceae (R=0.386, P=0.02). Lachnospiraceae decreased significantly in patients with cirrhosis (P=0.004) and correlated negatively with CTP score (R=-0.49, P=0.002). Using partial least square discriminate analysis, we identified 149 operational taxonomic units (OTUs) as key phylotypes that responded to cirrhosis, most of which were Lachnospiraceae (65 OTUs), Streptococcaceae (23 OTUs), and Veillonellaceae (21 OTUs). CONCLUSION: Fecal microbial communities are distinct in patients with cirrhosis compared with healthy individuals. The prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae and Streptococcaceae, with the reduction of beneficial populations such as Lachnospiraceae in patients with cirrhosis may affect prognosis.

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  • Patients with cirrhosis have reduced abundance of beneficial gut bacteria such as Lachnospiraceae.

    “At the same time, there is decreased abundance of beneficial bacteria in the gut, such as Lachnospiraceae33.”
  • Cirrhosis stage correlates positively with Enterobacteriaceae and negatively with Lachnospiraceae.

    “These changes seem to develop progressively, as cirrhosis stage is positively correlated with Enterobacteriaceae and negatively correlated with Lachnospiraceae33,34.”
  • Patients with cirrhosis have increased Enterobacteriaceae and oral-type taxa such as Veillonellaceae and Streptococcaceae, consistent with microorganisms moving from the mouth to the gut.

    “Studies in the past few years have demonstrated profound alterations of the intestinal microbiota in patients with cirrhosis, showing increased Enterobacteriacea as well as strains that are typically found in the oral microbiota, such as Veillonellaceae and Streptococcaceae, consistent with an invasion of microorganisms from the mouth to the gut in liver cirrhosis32,33.”
  • Chen et al. found a similar Chao index in cirrhotic patients and a non-significant Shannon index when compared to healthy controls.

    “Chen et al.51 found a similar Chao index in cirrhotic patients and a non-significant Shannon index when compared to healthy controls.”
  • The composition of the microbiome was altered in all these patients regardless of the lack of statistically significant changes in diversity.

    “the composition of the microbiome was altered in all these patients regardless of the lack of statistically significant changes in diversity”

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Research works printed but not linked: 42

  1. Garcia-Tsao G, Wiest R. Gut microflora in the pathogenesis of the complications of cirrhosis. Best Pract Res Clin Gastroenterol 2004;18: 353-372.
  2. Riordan SM, Williams R. Gut flora and hepatic encephalopathy in patients with cirrhosis. N Engl J Med 2010;362:1140-1142.
  3. Berg RD, Garlington AW. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun 1979;23:403-411.
  4. Wiest R, Das S, Cadelina G, Garcia-Tsao G, Milstien S, Groszmann RJ. Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility. J Clin Invest 1999;104:1223-1233.
  5. Tazi KA, Moreau R, Herve P, Dauvergne A, Cazals-Hatem D, Bert F, et al. Norfloxacin reduces aortic NO synthases and proinflammatory cytokine up-regulation in cirrhotic rats: role of Akt signaling. Gastroen- terology 2005;129:303-314.
  6. Zeuzem S. Gut-liver axis. Int J Colorectal Dis 2000;15:59-82.
  7. Norman K, Pirlich M. Gastrointestinal tract in liver disease: which organ is sick? Curr Opin Clin Nutr Metab Care 2008;11:613-619.
  8. Grange JD, Roulot D, Pelletier G, Pariente EA, Denis J, Ink O, et al. Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial. J Hepatol 1998; 29:430-436.
  9. Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Syn- biotic modulation of gut flora: effect on minimal hepatic encephalop- athy in patients with cirrhosis. HEPATOLOGY 2004;39:1441-1449.
  10. Novella M, Sola R, Soriano G, Andreu M, Gana J, Ortiz J, et al. Con- tinuous versus inpatient prophylaxis of the first episode of spontaneous bacterial peritonitis with norfloxacin. HEPATOLOGY 1997;25:532-536.
  11. Rasaratnam B, Kaye D, Jennings G, Dudley F, Chin-Dusting J. The effect of selective intestinal decontamination on the hyperdynamic cir- culatory state in cirrhosis. A randomized trial. Ann Intern Med 2003; 139:186-193.
  12. Floch MH, Katz J, Conn HO. Qualitative and quantitative relation- ships of the fecal flora in cirrhotic patients with portal systemic ence- phalopathy and following portacaval anastomosis. Gastroenterology 1970;59:70-75.
  13. Mai V, Morris JG Jr. Colonic bacterial flora: changing understandings in the molecular age. J Nutr 2004;134:459-464.
  14. Zoetendal EG, Collier CT, Koike S, Mackie RI, Gaskins HR. Molecu- lar ecological analysis of the gastrointestinal microbiota: a review. J Nutr 2004;134:465-472.
  15. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science 2005;308:1635-1638.
  16. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006;124: 837-848.
  17. Cucchiara S, Iebba V, Conte MP, Schippa S. The microbiota in inflam- matory bowel disease in different age groups. Dig Dis 2009;27: 252-258.
  18. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 2009;106:2365-2370.
  19. Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 2010;5: e9085.
  20. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 2005;437:376-380.
  21. Liu Z, Lozupone C, Hamady M, Bushman FD, Knight R. Short pyro- sequencing reads suffice for accurate microbial community analysis. Nucleic Acids Res 2007;35:e120.
  22. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646-649.
  23. Muyzer G, de Waal EC, Uitterlinden AG. Profiling of complex micro- bial populations by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA. Appl Environ Microbiol 1993;59:695-700.
  24. Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 2004;70: 6459-6465.
  25. Walter J, Hertel C, Tannock GW, Lis CM, Munro K, Hammes WP. Detection of Lactobacillus, Pediococcus, Leuconostoc, and Weissella species in human feces by using group-specific PCR primers and dena- turing gradient gel electrophoresis. Appl Environ Microbiol 2001;67: 2578-2585.
  26. McKenna P, Hoffmann C, Minkah N, Aye PP, Lackner A, Liu Z, et al. The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS Pathog 2008;4:e20.
  27. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 2008;6:e280.
  28. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature 2009;457:480-484.
  29. Karlsson C, Ahrne S, Molin G, Berggren A, Palmquist I, Fredrikson GN, et al. Probiotic therapy to men with incipient arteriosclerosis ini- tiates increased bacterial diversity in colon: a randomized controlled trial. Atherosclerosis 2009;208:228-233.
  30. Guarner C, Runyon BA, Young S, Heck M, Sheikh MY. Intestinal bac- terial overgrowth and bacterial translocation in cirrhotic rats with asci- tes. J Hepatol 1997;26:1372-1378.
  31. Riordan SM, Williams R. The intestinal flora and bacterial infection in cirrhosis. J Hepatol 2006;45:744-757.
  32. Bauer TM, Steinbruckner B, Brinkmann FE, Ditzen AK, Schwacha H, Aponte JJ, et al. Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. Am J Gastroenterol 2001;96:2962-2967.
  33. Justesen T, Nielsen OH, Jacobsen IE, Lave J, Rasmussen SN. The nor- mal cultivable microflora in upper jejunal fluid in healthy adults. Scand J Gastroenterol 1984;19:279-282.
  34. Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006;40:235-243.
  35. Vince AJ, McNeil NI, Wager JD, Wrong OM. The effect of lactulose, pectin, arabinogalactan and cellulose on the production of organic acids and metabolism of ammonia by intestinal bacteria in a faecal incuba- tion system. Br J Nutr 1990;63:17-26.
  36. Llovet JM, Bartoli R, March F, Planas R, Vinado B, Cabre E, et al. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. J Hepatol 1998;28: 307-313.
  37. Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P. In- testinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp Res 2009;33:1836-1846.
  38. Yan AW, Fouts DE, Brandl J, Starkel P, Torralba M, Schott E, et al. Enteric dysbiosis associated with a mouse model of alcoholic liver dis- ease. HEPATOLOGY 2011;53:96-105.
  39. Utne HE, Winkler K. Hepatic and extrahepatic elimination of ethanol in cirrhosis. With estimates of intrahepatic shunts and Km for ethanol elimination. Scand J Gastroenterol 1980;15:297-304.
  40. Tillonen J, Homann N, Rautio M, Jousimies-Somer H, Salaspuro M. Ciprofloxacin decreases the rate of ethanol elimination in humans. Gut 1999;44:347-352.
  41. Salaspuro V, Nyfors S, Heine R, Siitonen A, Salaspuro M, Jousimies- Somer H. Ethanol oxidation and acetaldehyde production in vitro by human intestinal strains of Escherichia coli under aerobic, microaero- bic, and anaerobic conditions. Scand J Gastroenterol 1999;34:967-973.
  42. Zhang C, Zhang M, Wang S, Han R, Cao Y, Hua W, et al. Interac- tions between gut microbiota, host genetics and diet relevant to devel- opment of metabolic syndromes in mice. ISME J 2010;4:232-241.

Cited by

Sorted by citations

Authors
Chen, Y., Yang, F., Lu, H., Wang, B., Chen, Y., Lei, D., Wang, Y., Zhu, B., & Li, L.
Affiliations
  • First Affiliated Hospital Zhejiang University (CN)
  • Chinese National Human Genome Center at Shanghai (CN)
  • Chinese Academy of Sciences (CN)
Corresponding author
  • Zhu, Baoli
  • Li, Lanjuan
Venue
Hepatology
Published
2011-08
Volume
54
Issue
2
Pages
562-572
ISSN
0270-9139 (ISSN-L)
OpenAlex
W2051567523
Cited by
1,038
References
4
Citations by year
2026: 38 · 2025: 66 · 2024: 77 · 2023: 119 · 2022: 103 · 2021: 101 · 2020: 108 · 2019: 85 · 2018: 96 · 2017: 68 · 2016: 40 · 2015: 55 · 2014: 33 · 2013: 27 · 2012: 17
FWCI
10.58
Type
journal article
Language
en
Open access
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
  • Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
Keywords
liver cirrhosis, gut microbiota, Bacteroidetes, Lachnospiraceae, Streptococcaceae, Veillonellaceae, Enterobacteriaceae, Fusobacteria, Proteobacteria, Child-Pugh score, gut dysbiosis, cirrhosis complications
MeSH terms
Bacteria, Feces, Female, Humans, Liver Cirrhosis, Male, Middle Aged

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