Alterations of the human gut microbiome in liver cirrhosis
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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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.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [32]
Metagenomic studies have revealed substantial alterations in gut microbiota composition across a range of chronic liver diseases and in patients with cirrhosis.
“Metagenomic studies have revealed substantial alterations in the composition of the gut microbiota in a range of CLD as well as in patients with cirrhosis12,32.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [32]
Key changes in the intestinal microbiota in cirrhosis include enrichment of Veillonella or Streptococcus and decreased bacteria from the order Clostridiales.
“Key changes in the composition of the intestinal microbiota in cirrhosis include enrichment of Veillonella or Streptococcus as well as decreased bacteria from the order Clostridiales32.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [32]
The majority of patient-enriched species in cirrhosis are of buccal origin, suggesting invasion of the gut from the mouth.
“Of note, the majority of the patient-enriched species were of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis32.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [32]
The gut microbiomes of patients with advanced liver disease and cirrhosis are characterized by increased potentially pathogenic bacteria and reduced beneficial bacteria.
“The gut microbiomes of patients with advanced liver disease and cirrhosis are characterized by an increase in potentially pathogenic bacteria, along with reduced numbers of bacteria with beneficial properties32,84,85.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [32]
Changes in the composition of the oral microbiome and colonisation of the lower intestinal tract by oral-specific bacteria are related to cirrhosis.
“Changes in the composition of the oral microbiome and the colonisation of the lower intestinal tract by oral-specific bacteria has been related to cirrhosis49.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [49]
Prevotella is increased in cirrhotics.
“Increased presence of Prevotella has been found in cirrhotics49”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [49]
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“not CRC), we compiled a list of known disease-associated markers from each of the original studies (Feng et al., 2015; Franzosa et al., 2019; Karlsson et al., 2013; Qin et al., 2012; Qin et al., 2014).”
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Gut dysbiosis associated with hepatitis C virus infection
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Gut Metagenomics-Derived Genes as Potential Biomarkers of Parkinson’s Disease
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Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
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Microbiota, a key player in alcoholic liver disease
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The Commensal Microbe V eillonella as a Marker for Response to an FGF19 Analog in NASH
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Oral and Gut Dysbiosis Leads to Functional Alterations in Parkinson’s Disease
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Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact
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Advances in Gut Microbiota of Viral Hepatitis Cirrhosis
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Deciphering mechanisms and implications of bacterial translocation in human health and disease
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“8) (Figure S6).(51,52) Our results suggest that preexisting cirrhosis-related dysbiosis may blur the”
ResultThe Human Gut Microbiome in Liver Diseases
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- Authors
- Qin, N., Yang, F., Li, A., Prifti, E., Chen, Y., Shao, L., Guo, J., Le Chatelier, E., Yao, J., Wu, L., Zhou, J., Ni, S., Liu, L., Pons, N., Batto, J. M., Kennedy, S. P., Leonard, P., Yuan, C., Ding, W., Chen, Y., Hu, X., Zheng, B., Qian, G., Xu, W., Ehrlich, S. D., Zheng, S., & Li, L.
- Affiliations
- First Affiliated Hospital Zhejiang University (CN)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Guy's Hospital (GB)
- Corresponding author
- Ehrlich, S. Dusko
- Zheng, Shusen
- Li, Lanjuan
- ORCID
- Venue
- Nature
- Published
- 2014-07-23
- Volume
- 513
- Issue
- 7516
- Pages
- 59-64
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1964027278
- Cited by
- 2,177
- References
- 56
- Citations by year
- 2026: 136 · 2025: 174 · 2024: 215 · 2023: 214 · 2022: 226 · 2021: 283 · 2020: 235 · 2019: 201 · 2018: 161 · 2017: 136 · 2016: 98 · 2015: 83 · 2014: 10
- FWCI
- 44.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-DPBS-0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- liver cirrhosis, gut microbiota, microbiome biomarkers, oral bacteria, Veillonella, Streptococcus, diagnostic biomarkers, novel genes, type 2 diabetes, inflammatory bowel disease
- MeSH terms
- Chronic Disease, Diabetes Mellitus, Type 2, Feces, Genetic Markers, Health, Humans, Liver Cirrhosis, Mouth, Phylogeny, Reproducibility of Results, Inflammatory Bowel Diseases, Case-Control Studies, Gastrointestinal Tract, Metagenomics, Microbiota
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