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Interactions Between the Intestinal Microbiome and Liver Diseases
Open accessAbstract
The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to nonalcoholic fatty liver disease, steatohepatitis, alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease.
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“the impact of changes to the composition and function of the microbiome in NASH include altered bile acid metabolism and loss of integrity of the gut-vascular barrier, precipitating leakage of LPS and bacteria into the liver via the portal circulation (14–16).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [14]
Experimental — accuracy not yet measuredIn the citing paper
“Changes in gut microbiota (dysbiosis) may play a key role in the pathogenesis of NAFLD/NASH and cholestasis52–54 and may also impact on BA composition and signalling.51 55”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [54]
In the citing paper
“However, a failing gut barrier and alterations of the gut microbiota in chronic liver disease (CLD) contribute to chronic inflammation and the progression of liver diseases12, and thereby increase risk for the development of hepatocellular carcinoma (HCC) as the final stage of the disease process 13–15.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [12]
In the citing paper
“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 [12]
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“Recent animal studies have placed the gut microbiota as a potentially important player in the pathogenesis of NAFLD.((14,15)) However, data linking gut dysbiosis with the severity of NAFLD remain poorly documented in humans.”
BackgroundThe gut-liver axis and the intersection with the microbiome
Tripathi, A., Debelius, J., Brenner, D. A., Karin, M., Loomba, R., Schnabl, B., & Knight, R. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0011-z · Cited by 1,480
Self-citationLiver inflammation and fibrosis
Koyama, Y., & Brenner, D. A. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88881 · Cited by 1,295
Self-citationHepatic inflammation and fibrosis: Functional links and key pathways
Seki, E., & Schwabe, R. F. (2015) · Hepatology · doi:10.1002/hep.27332 · Cited by 972
Metadata
- Authors
- Schnabl, B., & Brenner, D. A.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Schnabl, Bernd
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 146
- Issue
- 6
- Pages
- 1513-1524
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3996054
- OpenAlex
- W1975691929
- Cited by
- 971
- References
- 86
- Citations by year
- 2026: 37 · 2025: 56 · 2024: 88 · 2023: 101 · 2022: 88 · 2021: 92 · 2020: 102 · 2019: 88 · 2018: 89 · 2017: 58 · 2016: 64 · 2015: 77 · 2014: 31
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (U01 AA021856, R01 AA020703, 2 P42 ES010337, K08 DK081830)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- gut microbiota, gut-liver axis, non-alcoholic fatty liver disease, steatohepatitis, alcoholic liver disease, liver cirrhosis, dysbiosis, intestinal homeostasis, intestinal barrier dysfunction, intestinal inflammation, microbial translocation, microbial metabolites, Western diet, alcohol
- MeSH terms
- Animals, Bacteria, Bile Acids and Salts, Fatty Liver, Humans, Intestines, Liver Cirrhosis, Liver Diseases, Liver Diseases, Alcoholic, Risk Factors, Host-Pathogen Interactions, Microbiota, Dysbiosis, Non-alcoholic Fatty Liver Disease
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