Skip to main content

Advertisement

Springer Nature Link
Log in

Changes of Fecal Bifidobacterium Species in Adult Patients with Hepatitis B Virus-Induced Chronic Liver Disease

  • Host Microbe Interactions
  • Published:
Microbial Ecology Aims and scope Submit manuscript

Abstract

The beneficial effects of Bifidobacteria on health have been widely accepted. Patients with chronic liver disease have varying degrees of intestinal microflora imbalance with a decrease of total Bifidobacterial counts. Since different properties have been attributed to different Bifidobacterium species and there is no information available for the detailed changes in the genus Bifidobacterium in patients with chronic liver disease heretofore, it is meaningful to investigate the structure of this bacterium at the species level in these patients. The aim of this study was to characterize the composition of intestinal Bifidobacterium in patients with hepatitis B virus-induced chronic liver disease. Nested-PCR-based denaturing gradient gel electrophoresis (PCR-DGGE), clone library, and real-time quantitative PCR were performed on the fecal samples of 16 patients with chronic hepatitis B (CHB patients), 16 patients with hepatitis B virus-related cirrhosis (HBV cirrhotics), and 15 healthy subjects (Controls). Though there was no significant difference in the diversity among the three groups (P = 0.196), Bifidobacterium dentium seems to be specifically enhanced in patients as the PCR-DGGE profiles showed, which was further validated by clone library and real-time quantitative PCR. In contrast to the B. dentium, Bifidobacterium catenulatum/Bifidobacterium pseudocatenulatum were detected less frequently in the predominant profile and by quantitative PCR in HBV cirrhotics than in the controls, and the level of this species was also significantly different between these two groups (P = 0.023). Although having no quantitative difference among the three groups, Bifidobacterium longum was less commonly detected in HBV cirrhotics than in CHB patients and Controls by quantitative PCR (P = 0.011). Thus, the composition of intestinal Bifidobacterium was deeply altered in CHB and HBV cirrhotic patients with a shift from beneficial species to opportunistic pathogens. The results provide further insights into the dysbiosis of the intestinal microbiota in patients with hepatitis B virus-induced chronic liver disease and might potentially serve as guidance for the probiotics interventions of these diseases.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Lavanchy D (2004) Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 11:97–107

    Article  PubMed  CAS  Google Scholar 

  2. Garcia-Tsao G, Wiest R (2004) Gut microflora in the pathogenesis of the complications of cirrhosis. Best Pract Res Clin Gastroenterol 18:353–372

    Article  PubMed  Google Scholar 

  3. Norman K, Pirlich M (2008) Gastrointestinal tract in liver disease: which organ is sick? Curr Opin Clin Nutr Metab Care 11:613–619

    Article  PubMed  Google Scholar 

  4. Riordan SM, Williams R (2006) The intestinal flora and bacterial infection in cirrhosis. J Hepatol 45:744–757

    Article  PubMed  Google Scholar 

  5. Trebichavsky I, Rada V, Splichalova A, Splichal I (2009) Cross-talk of human gut with bifidobacteria. Nutr Rev 67:77–82

    Article  PubMed  Google Scholar 

  6. Mitsuoka T (1990) Bifidobacteria and their role in human health. J Ind Microbiol 6:263–267

    Article  Google Scholar 

  7. Fyderek K, Strus M, Kowalska-Duplaga K, Gosiewski T, Wedrychowicz A, Jedynak-Wasowicz U, Sladek M, Pieczarkowski S, Adamski P, Kochan P, Heczko PB (2009) Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease. World J Gastroenterol 15:5287–5294

    Article  PubMed  Google Scholar 

  8. Kerckhoffs AP, Samsom M, van der Rest ME, de Vogel J, Knol J, Ben-Amor K, Akkermans LM (2009) Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients. World J Gastroenterol 15:2887–2892

    Article  PubMed  Google Scholar 

  9. Li L, Wu Z, Ma W, Yu Y, Chen Y (2001) Changes in intestinal microflora in patients with chronic severe hepatitis. Chin Med J (Engl) 114:869–872

    CAS  Google Scholar 

  10. 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 

  11. Lu H, Wu Z, Xu W, Yang J, Chen Y, Li L (2011) Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection: intestinal microbiota of HBV cirrhotic patients. Microb Ecol 61(3):693–703

    Article  PubMed  Google Scholar 

  12. Lopez P, Gueimonde M, Margolles A, Suarez A (2010) Distinct Bifidobacterium strains drive different immune responses in vitro. Int J Food Microbiol 138:157–165

    Article  PubMed  CAS  Google Scholar 

  13. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Jian M, Zhou Y, Li Y, Zhang X, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Bork P, Ehrlich SD (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65

    Article  PubMed  CAS  Google Scholar 

  14. Ley RE, Hamady M, Lozupone C, Turnbaugh PJ, Ramey RR, Bircher JS, Schlegel ML, Tucker TA, Schrenzel MD, Knight R, Gordon JI (2008) Evolution of mammals and their gut microbes. Science 320:1647–1651

    Article  PubMed  CAS  Google Scholar 

  15. 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  PubMed  CAS  Google Scholar 

  16. Turroni F, Marchesi JR, Foroni E, Gueimonde M, Shanahan F, Margolles A, van Sinderen D, Ventura M (2009) Microbiomic analysis of the bifidobacterial population in the human distal gut. ISME J 3:745–751

    Article  PubMed  CAS  Google Scholar 

  17. Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y (2008) Imbalances in faecal and duodenal Bifidobacterium species composition in active and non-active coeliac disease. BMC Microbiol 8:232

    Article  PubMed  Google Scholar 

  18. Ramirez-Farias C, Slezak K, Fuller Z, Duncan A, Holtrop G, Louis P (2009) Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. Br J Nutr 101:541–550

    Article  PubMed  CAS  Google Scholar 

  19. Martin R, Jimenez E, Heilig H, Fernandez L, Marin ML, Zoetendal EG, Rodriguez JM (2009) Isolation of bifidobacteria from breast milk and assessment of the bifidobacterial population by PCR-denaturing gradient gel electrophoresis and quantitative real-time PCR. Appl Environ Microbiol 75:965–969

    Article  PubMed  CAS  Google Scholar 

  20. Kuhbacher T, Ott SJ, Helwig U, Mimura T, Rizzello F, Kleessen B, Gionchetti P, Blaut M, Campieri M, Folsch UR, Kamm MA, Schreiber S (2006) Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis. Gut 55:833–841

    Article  PubMed  CAS  Google Scholar 

  21. Matsuki T, Watanabe K, Fujimoto J, Kado Y, Takada T, Matsumoto K, Tanaka R (2004) Quantitative PCR with 16S rRNA-gene-targeted species-specific primers for analysis of human intestinal bifidobacteria. Appl Environ Microbiol 70:167–173

    Article  PubMed  CAS  Google Scholar 

  22. Zhuang H (2007) Guideline on prevention and treatment of chronic hepatitis B in China (2005). Chinese Med J-Peking 120:2159–2173

    CAS  Google Scholar 

  23. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649

    Article  PubMed  CAS  Google Scholar 

  24. Nielsen DS, Moller PL, Rosenfeldt V, Paerregaard A, Michaelsen KF, Jakobsen M (2003) Case study of the distribution of mucosa-associated Bifidobacterium species, Lactobacillus species, and other lactic acid bacteria in the human colon. Appl Environ Microbiol 69:7545–7548

    Article  PubMed  CAS  Google Scholar 

  25. Satokari RM, Vaughan EE, Akkermans AD, Saarela M, de Vos WM (2001) Bifidobacterial diversity in human feces detected by genus-specific PCR and denaturing gradient gel electrophoresis. Appl Environ Microbiol 67:504–513

    Article  PubMed  CAS  Google Scholar 

  26. Simpson JM, McCracken VJ, Gaskins HR, Mackie RI (2000) Denaturing gradient gel electrophoresis analysis of 16S ribosomal DNA amplicons to monitor changes in fecal bacterial populations of weaning pigs after introduction of Lactobacillus reuteri strain MM53. Appl Environ Microbiol 66:4705–4714

    Article  PubMed  CAS  Google Scholar 

  27. Ritchie LE, Steiner JM, Suchodolski JS (2008) Assessment of microbial diversity along the feline intestinal tract using 16S rRNA gene analysis. FEMS Microbiol Ecol 66:590–598

    Article  PubMed  CAS  Google Scholar 

  28. Schloss PD, Handelsman J (2005) Introducing DOTUR, a computer program for defining operational taxonomic units and estimating species richness. Appl Environ Microbiol 71:1501–1506

    Article  PubMed  CAS  Google Scholar 

  29. Pei CX, Liu Q, Dong CS, Li H, Jiang JB, Gao WJ (2010) Diversity and abundance of the bacterial 16S rRNA gene sequences in forestomach of alpacas (Lama pacos) and sheep (Ovis aries). Anaerobe 16:426–432

    Article  PubMed  CAS  Google Scholar 

  30. Sanz Y, Sanchez E, Marzotto M, Calabuig M, Torriani S, Dellaglio F (2007) Differences in faecal bacterial communities in coeliac and healthy children as detected by PCR and denaturing gradient gel electrophoresis. FEMS Immunol Med Microbiol 51:562–568

    Article  PubMed  CAS  Google Scholar 

  31. Sheth AA, Garcia-Tsao G (2008) Probiotics and liver disease. J Clin Gastroenterol 42(Suppl 2):S80–S84

    Article  PubMed  Google Scholar 

  32. Malaguarnera M, Greco F, Barone G, Gargante MP, Toscano MA (2007) Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig Dis Sci 52:3259–3265

    Article  PubMed  Google Scholar 

  33. Matsuki T, Watanabe K, Tanaka R, Fukuda M, Oyaizu H (1999) Distribution of bifidobacterial species in human intestinal microflora examined with 16S rRNA-gene-targeted species-specific primers. Appl Environ Microbiol 65:4506–4512

    PubMed  CAS  Google Scholar 

  34. Beighton D, Gilbert SC, Clark D, Mantzourani M, Al-Haboubi M, Ali F, Ransome E, Hodson N, Fenlon M, Zoitopoulos L, Gallagher J (2008) Isolation and identification of bifidobacteriaceae from human saliva. Appl Environ Microbiol 74:6457–6460

    Article  PubMed  CAS  Google Scholar 

  35. Hojo K, Nagaoka S, Murata S, Taketomo N, Ohshima T, Maeda N (2007) Reduction of vitamin K concentration by salivary Bifidobacterium strains and their possible nutritional competition with Porphyromonas gingivalis. J Appl Microbiol 103:1969–1974

    Article  PubMed  CAS  Google Scholar 

  36. Mantzourani M, Gilbert SC, Sulong HN, Sheehy EC, Tank S, Fenlon M, Beighton D (2009) The isolation of bifidobacteria from occlusal carious lesions in children and adults. Caries Res 43:308–313

    Article  PubMed  CAS  Google Scholar 

  37. Nakajo K, Takahashi N, Beighton D (2010) Resistance to acidic environments of caries-associated bacteria: Bifidobacterium dentium and Bifidobacterium longum. Caries Res 44:431–437

    Article  PubMed  CAS  Google Scholar 

  38. Gueimonde M, Debor L, Tolkko S, Jokisalo E, Salminen S (2007) Quantitative assessment of faecal bifidobacterial populations by real-time PCR using lanthanide probes. J Appl Microbiol 102:1116–1122

    PubMed  CAS  Google Scholar 

  39. Ventura M, Turroni F, Zomer A, Foroni E, Giubellini V, Bottacini F, Canchaya C, Claesson MJ, He F, Mantzourani M, Mulas L, Ferrarini A, Gao B, Delledonne M, Henrissat B, Coutinho P, Oggioni M, Gupta RS, Zhang Z, Beighton D, Fitzgerald GF, O’Toole PW, van Sinderen D (2009) The Bifidobacterium dentium Bd1 genome sequence reflects its genetic adaptation to the human oral cavity. PLoS Genet 5:e1000785

    Article  PubMed  Google Scholar 

  40. Fardini Y, Chung P, Dumm R, Joshi N, Han YW (2010) Transmission of diverse oral bacteria to murine placenta: evidence for the oral microbiome as a potential source of intrauterine infection. Infect Immun 78:1789–1796

    Article  PubMed  CAS  Google Scholar 

  41. Li YT, Wang L, Chen Y, Chen YB, Wang HY, Wu ZW, Li LJ (2010) Effects of gut microflora on hepatic damage after acute liver injury in rats. J Trauma 68:76–83

    Article  PubMed  Google Scholar 

  42. Xing HC, Li LJ, Xu KJ, Shen T, Chen YB, Sheng JF, Chen Y, Fu SZ, Chen CL, Wang JG, Yan D, Dai FW, Zheng SS (2006) Protective role of supplement with foreign Bifidobacterium and Lactobacillus in experimental hepatic ischemia-reperfusion injury. J Gastroenterol Hepatol 21:647–656

    Article  PubMed  Google Scholar 

  43. Romond MB, Haddou Z, Mielcareck C, Romond C (1997) Bifidobacteria and human health: regulatory effect of indigenous bifidobacteria on Escherichia coli intestinal colonization. Anaerobe 3:131–136

    Article  PubMed  CAS  Google Scholar 

  44. Matsumoto T, Ishikawa H, Tateda K, Yaeshima T, Ishibashi N, Yamaguchi K (2008) Oral administration of Bifidobacterium longum prevents gut-derived Pseudomonas aeruginosa sepsis in mice. J Appl Microbiol 104:672–680

    Article  PubMed  CAS  Google Scholar 

  45. Han SY, Huh CS, Ahn YT, Lim KS, Baek YJ, Kim DH (2005) Hepatoprotective effect of lactic acid bacteria, inhibitors of beta-glucuronidase production against intestinal microflora. Arch Pharm Res 28:325–329

    Article  PubMed  CAS  Google Scholar 

  46. Roger LC, Costabile A, Holland DT, Hoyles L, McCartney AL (2010) Examination of faecal Bifidobacterium populations in breast- and formula-fed infants during the first 18 months of life. Microbiology 156:3329–3341

    Article  PubMed  CAS  Google Scholar 

  47. Kulagina EV, Shkoporov AN, Kafarskaia LI, Khokhlova EV, Volodin NN, Donskikh EE, Korshunova OV, Efimov BA (2010) Molecular genetic study of species and strain variability in bifidobacteria population in intestinal microflora of breast-fed infants and their mothers. Bull Exp Biol Med 150:61–64

    Article  PubMed  CAS  Google Scholar 

  48. Delgado S, Suarez A, Mayo B (2006) Bifidobacterial diversity determined by culturing and by 16S rDNA sequence analysis in feces and mucosa from ten healthy Spanish adults. Dig Dis Sci 51:1878–1885

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Basic Research Program (973) of China (2007CB513003 and 2009CB522406) and Zhejiang Public Health Bureau Fund (2008QN010). We thank Dr. Wei Chen for critical reading and useful suggestions.

Author information

Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, People’s Republic of China

    Min Xu, Baohong Wang, Yanfei Chen, Fengling Yang, Haifeng Lu, Yunbo Chen, Jiali Xu & Lanjuan Li

  2. Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China

    Yiqi Fu

Authors
  1. Min Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baohong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yiqi Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanfei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fengling Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haifeng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yunbo Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jiali Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lanjuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lanjuan Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, M., Wang, B., Fu, Y. et al. Changes of Fecal Bifidobacterium Species in Adult Patients with Hepatitis B Virus-Induced Chronic Liver Disease. Microb Ecol 63, 304–313 (2012). https://doi.org/10.1007/s00248-011-9925-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00248-011-9925-5

Keywords

Search

Navigation