Alterations of the human gut microbiome in liver cirrhosis

• Published in: Nature (London) Vol. 513; no. 7516; pp. 59 - 64
• Main Authors: Qin, Nan, Yang, Fengling, Li, Ang, Prifti, Edi, Chen, Yanfei, Shao, Li, Guo, Jing, Le Chatelier, Emmanuelle, Yao, Jian, Wu, Lingjiao, Zhou, Jiawei, Ni, Shujun, Liu, Lin, Pons, Nicolas, Batto, Jean Michel, Kennedy, Sean P., Leonard, Pierre, Yuan, Chunhui, Ding, Wenchao, Chen, Yuanting, Hu, Xinjun, Zheng, Beiwen, Qian, Guirong, Xu, Wei, Ehrlich, S. Dusko, Zheng, Shusen, Li, Lanjuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-09-2014; Nature Publishing Group
• Subjects: 45; 45/23; 45/43; 631/114/2785; 631/326; 692/53; Case-Control Studies; Chronic Disease; Diabetes Mellitus, Type 2 - microbiology; Digestive system; Feces - microbiology; Gastrointestinal Tract - microbiology; Genes; Genetic Markers - genetics; Health; Humanities and Social Sciences; Humans; Inflammatory Bowel Diseases - microbiology; Invasive species; Life Sciences; Liver; Liver cirrhosis; Liver Cirrhosis - diagnosis; Liver Cirrhosis - microbiology; Medical research; Medicine, Experimental; Metagenomics; Microbiota (Symbiotic organisms); Microbiota - genetics; Microbiota - physiology; Microorganisms; Mouth - microbiology; multidisciplinary; Phylogenetics; Phylogeny; Physiological aspects; Reproducibility of Results; Science; Studies; China
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13568

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.
Invasion of the gut by oral bacteria in liver cirrhosis.
Liver cirrhosis link to the gut microbiome
Previous work has revealed an association between liver complications such as cirrhosis and the gut microbiome. Lanjuan Li and colleagues undertook a microbiome-wide association study of stool samples from 98 liver cirrhosis patients and 83 healthy controls. Quantitative metagenomics analysis revealed 75,245 genes that were significantly different in abundance between the two groups, many of which could be grouped into 66 clusters that represent cognate bacterial species. Of these, 28 species were enriched in liver cirrhosis patients and most were of buccal origin (mostly
Veillonella
and streptococci). The identified markers were unique liver cirrhosis-specific genes and the authors identify a set of just 15 of these genes that could form the basis of a highly accurate discrimination index that could be used as a diagnostic tool.