Alterations of the human gut microbiome in liver cirrhosis

被引:1890
作者
Qin, Nan [1 ,2 ]
Yang, Fengling [1 ]
Li, Ang [1 ]
Prifti, Edi [3 ]
Chen, Yanfei [1 ]
Shao, Li [1 ,2 ]
Guo, Jing [1 ]
Le Chatelier, Emmanuelle [3 ]
Yao, Jian [1 ,2 ]
Wu, Lingjiao [1 ]
Zhou, Jiawei [1 ]
Ni, Shujun [1 ]
Liu, Lin [1 ]
Pons, Nicolas [3 ]
Batto, Jean Michel [3 ]
Kennedy, Sean P. [3 ]
Leonard, Pierre [3 ]
Yuan, Chunhui [1 ]
Ding, Wenchao [1 ]
Chen, Yuanting [1 ]
Hu, Xinjun [1 ]
Zheng, Beiwen [1 ,2 ]
Qian, Guirong [1 ]
Xu, Wei [1 ]
Ehrlich, S. Dusko [3 ,4 ]
Zheng, Shusen [2 ,5 ]
Li, Lanjuan [1 ,2 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 1, Coll Med, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China
[2] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China
[3] INRA, Metagenopolis, F-78350 Jouy En Josas, France
[4] Kings Coll London, Dent Inst Cent Off, Guys Hosp, Ctr Host Microbiome Interact, London SE1 9RT, England
[5] Zhejiang Univ, Affiliated Hosp 1, Minist Publ Hlth, Key Lab Combined Multiorgan Transplantat, Hangzhou 310003, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
BACTERIAL TRANSLOCATION; INTESTINAL MICROBIOTA; OBESITY; CATALOG; GENOMES; IMPACT; LONG;
D O I
10.1038/nature13568
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:59 / +
页数:19
相关论文
共 55 条
[1]
Genome sequences of rare, uncultured bacteria obtained by differential coverage binning of multiple metagenomes [J].
Albertsen, Mads ;
Hugenholtz, Philip ;
Skarshewski, Adam ;
Nielsen, Kare L. ;
Tyson, Gene W. ;
Nielsen, Per H. .
NATURE BIOTECHNOLOGY, 2013, 31 (06) :533-+
[2]
Rifaximin Treatment in Hepatic Encephalopathy [J].
Bass, Nathan M. ;
Mullen, Kevin D. ;
Sanyal, Arun ;
Poordad, Fred ;
Neff, Guy ;
Leevy, Carroll B. ;
Sigal, Samuel ;
Sheikh, Muhammad Y. ;
Beavers, Kimberly ;
Frederick, Todd ;
Teperman, Lewis ;
Hillebrand, Donald ;
Huang, Shirley ;
Merchant, Kunal ;
Shaw, Audrey ;
Bortey, Enoch ;
Forbes, William P. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (12) :1071-1081
[3]
Bauer TM, 2002, AM J GASTROENTEROL, V97, P2364
[4]
Gut microbiome and intestinal barrier failure - The "Achilles heel" in hepatology? [J].
Benten, Daniel ;
Wiest, Reiner .
JOURNAL OF HEPATOLOGY, 2012, 56 (06) :1221-1223
[5]
Gut microbiota and probiotics in chronic liver diseases [J].
Cesaro, Claudia ;
Tiso, Angelo ;
Del Prete, Anna ;
Cariello, Rita ;
Tuccillo, Concetta ;
Cotticelli, Gaetano ;
Blanco, Camillo del Vecchio ;
Loguercio, Carmelina .
DIGESTIVE AND LIVER DISEASE, 2011, 43 (06) :431-438
[6]
The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information [J].
Chen, Tsute ;
Yu, Wen-Han ;
Izard, Jacques ;
Baranova, Oxana V. ;
Lakshmanan, Abirami ;
Dewhirst, Floyd E. .
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION, 2010, :baq013
[7]
Characterization of Fecal Microbial Communities in Patients with Liver Cirrhosis [J].
Chen, Yanfei ;
Yang, Fengling ;
Lu, Haifeng ;
Wang, Baohong ;
Chen, Yunbo ;
Lei, Dajiang ;
Wang, Yuezhu ;
Zhu, Baoli ;
Li, Lanjuan .
HEPATOLOGY, 2011, 54 (02) :562-572
[8]
APPLICATIONS OF NEXT-GENERATION SEQUENCING The human microbiome: at the interface of health and disease [J].
Cho, Ilseung ;
Blaser, Martin J. .
NATURE REVIEWS GENETICS, 2012, 13 (04) :260-270
[9]
Dietary intervention impact on gut microbial gene richness [J].
Cotillard, Aurelie ;
Kennedy, Sean P. ;
Kong, Ling Chun ;
Prifti, Edi ;
Pons, Nicolas ;
Le Chatelier, Emmanuelle ;
Almeida, Mathieu ;
Quinquis, Benoit ;
Levenez, Florence ;
Galleron, Nathalie ;
Gougis, Sophie ;
Rizkalla, Salwa ;
Batto, Jean-Michel ;
Renault, Pierre ;
Dore, Joel ;
Zucker, Jean-Daniel ;
Clement, Karine ;
Ehrlich, Stanislav Dusko .
NATURE, 2013, 500 (7464) :585-+
[10]
Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa [J].
De Filippo, Carlotta ;
Cavalieri, Duccio ;
Di Paola, Monica ;
Ramazzotti, Matteo ;
Poullet, Jean Baptiste ;
Massart, Sebastien ;
Collini, Silvia ;
Pieraccini, Giuseppe ;
Lionetti, Paolo .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (33) :14691-14696