Abstract

Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.

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Accessions

Primary accessions

European Nucleotide Archive

Data deposits

The raw Illumina read data for all samples have been deposited in the European Bioinformatics Institute European Nucleotide Archive under accession number ERP005860.

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Acknowledgements

This work was supported by the National Program on Key Basic Research Project (2013CB531401), the National Natural Science Foundation of China (81301475 and 81330011), the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (81121002), the Technology Group Project for Infectious Disease Control of Zhejiang Province (2009R50041) and the Metagenopolis grant ANR-11-DPBS-0001. We thank Q. Cao, K. Su, J. Shao and A. Ghozlane for help with data computation, and H. Zhang, H. Lu, Q. Bao, J. Ge, J. Jiang, Z. Ren and M. Ye for assistance with sample collection. We are thankful to the MetaHIT consortium for generating the gut gene set and the Human Microbiome Project for generating the reference genomes from human gut microbes.

Author information

Author notes

    • Nan Qin
    • , Fengling Yang
    • , Ang Li
    • , Edi Prifti
    • , Yanfei Chen
    •  & Li Shao

    These authors contributed equally to this work.

Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China

    • Nan Qin
    • , Fengling Yang
    • , Ang Li
    • , Yanfei Chen
    • , Li Shao
    • , Jing Guo
    • , Jian Yao
    • , Lingjiao Wu
    • , Jiawei Zhou
    • , Shujun Ni
    • , Lin Liu
    • , Chunhui Yuan
    • , Wenchao Ding
    • , Yuanting Chen
    • , Xinjun Hu
    • , Beiwen Zheng
    • , Guirong Qian
    • , Wei Xu
    •  & Lanjuan Li
  2. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China

    • Nan Qin
    • , Li Shao
    • , Jian Yao
    • , Beiwen Zheng
    • , Shusen Zheng
    •  & Lanjuan Li
  3. Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France

    • Edi Prifti
    • , Emmanuelle Le Chatelier
    • , Nicolas Pons
    • , Jean Michel Batto
    • , Sean P. Kennedy
    • , Pierre Leonard
    •  & S. Dusko Ehrlich
  4. King’s College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy’s Hospital, London Bridge, London SE1 9RT, UK

    • S. Dusko Ehrlich
  5. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University, 310003 Hangzhou, China

    • Shusen Zheng

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Contributions

L.J.L., S.D.E., S.S.Z. and N.Q. designed the project. L.J.L., S.P.K. and N.Q. managed the project. F.L.Y., N.Q., Y.F.C., J.G., G.R.Q., X.J.H. and B.W.Z. collected samples and performed clinical study. J.G., Y.T.C. and W.X. performed DNA extraction experiments. Y.J., L.J.W., J.W.Z. and S.J.N. performed library construction and sequencing. L.J.L. and S.D.E. designed the analysis. N.Q., A.L., E.P., E.L.C., L.L., N.P., P.L., J.M.B., C.H.Y. and W.C.D. analysed the data. A.L. and N.Q. did the functional annotation analyses. L.S., E.P., E.L.C. and A.L. analysed the statistics. N.Q., F.L.Y., L.S. and E.P. wrote the paper. L.J.L. and S.D.E. revised the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to S. Dusko Ehrlich or Shusen Zheng or Lanjuan Li.

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DOI

https://doi.org/10.1038/nature13568

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