Gut-Liver Axis and Sensing Microbes
Open accessAbstract
‘Detoxification’ of gut-derived toxins and microbial products from gut-derived microbes is a major role of the liver. While the full repertoire of gut-derived microbial products that reach the liver in health and disease is yet to be explored, the levels of bacterial lipopolysaccharide (LPS), a component of Gram-negative bacteria, is increased in the portal and/or systemic circulation in several types of chronic liver diseases. Increased gut permeability and LPS play a role in alcoholic liver disease where alcohol impairs the gut epithelial integrity through alterations in tight junction proteins. In addition, non-alcoholic fatty liver disease is also associated with increased serum LPS levels and activation of the pro-inflammatory cascade plays a central role in disease progression. Microbial danger signals are recognized by pattern recognition receptors such as the Toll-like receptor 4 (TLR4). Increasing evidence suggests that TLR4-mediated signaling via the MyD88-dependent or MyD88-independent pathways may play different roles in liver diseases associated with increased LPS exposure of the liver as a result of gut permeability. For example, we showed that in alcoholic liver disease, the MyD88-independent, IRF3-dependent TLR4 cascade plays a role in steatosis and inflammation. Our recent data demonstrate that chronic alcohol exposure in the liver leads to sensitization of Kupffer cells to LPS via a mechanism involving upregulation of microRNA-155 in Kupffer cells. Thus, understanding the cell-specific recognition and intracellular signaling events in sensing gut-derived microbes will help to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases.
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Among the potential contributors of the microbiota to complications of liver cirrhosis is the presence of SIBO, and a dysfunctional mucosal barrier which can contribute to bacterial (or endotoxin) translocation to the portal circulation.
“Among the potential contributors of the microbiota to complications of liver cirrhosis is the presence of SIBO [73] , and a dysfunctional mucosal barrier which can contribute to bacterial (or endotoxin) translocation to the portal circulation [74] .”
From Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis (2014) · cites this paper as [74]
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- Authors
- Szabo, G., Bala, S., Petrasek, J., & Gattu, A.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Venue
- Digestive Diseases
- Publisher
- S. Karger AG
- Published
- 2010
- Volume
- 28
- Issue
- 6
- Pages
- 737-744
- ISSN
- 0257-2753 (ISSN-L)
- 1421-9875
- PMC
- PMC3211517
- OpenAlex
- W2067615993
- Cited by
- 179
- References
- 46
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 12 · 2023: 3 · 2022: 5 · 2021: 14 · 2020: 12 · 2019: 8 · 2018: 20 · 2017: 15 · 2016: 19 · 2015: 15 · 2014: 14 · 2013: 15 · 2012: 12
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Digestive Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA017729, AA017729, #AA011576, R01AA011576)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- gut-liver axis, lipopolysaccharide, bacterial endotoxemia, intestinal permeability, alcoholic liver disease, non-alcoholic fatty liver disease, TLR4, MyD88-independent signaling, IRF3, Kupffer cells, miR-155, steatosis, liver inflammation, pattern recognition receptors, tight junctions
- MeSH terms
- Animals, Disease, Homeostasis, Humans, Liver, Permeability, Gastrointestinal Tract, Metagenome
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