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The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression
Dishen Chen1, Thanh H Le1,2, Haleh Shahidipour1,3
1Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, NSW, Australia.
Abstract:
Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis.
Insights
Gut microbes entering circulation drive liver disease. Chronic liver disease increases gut permeability, allowing microbial translocation that worsens liver inflammation and fibrosis.
Area of Science:
- Gastroenterology and Hepatology
- Immunology
- Microbiology
Background:
- Intestinal dysbiosis is a key factor in gastrointestinal and liver diseases.
- The mechanism of microbial translocation from the gut to systemic circulation remains unclear.
- Chronic liver disease (CLD) exacerbates intestinal permeability, leading to increased microbial entry into the liver.
Purpose of the Study:
- To review the current understanding of microbial translocation in CLD.
- To examine the hepatic immune response to gut-derived antigens.
- To explore therapeutic strategies targeting intestinal permeability and immune responses in CLD.
Main Methods:
- Literature review of studies on microbial translocation in chronic liver disease.
- Analysis of the role of Kupffer and stellate cells in hepatic inflammation.
- Evaluation of current and emerging therapies for liver fibrosis.
Main Results:
- Increased intestinal permeability in CLD facilitates microbial translocation.
- Gut microbiota antigens activate hepatic immune cells, driving inflammation and fibrosis.
- Therapies targeting gut barrier function and immune responses show promise.
Conclusions:
- Microbial translocation is a critical pathway in CLD progression.
- Understanding hepatic immune responses to gut antigens is key for treatment.
- Targeting the gut-liver axis offers potential for managing liver fibrosis and cirrhosis.
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