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Intestinal Microbiome-Macrophage Crosstalk Contributes to Cholestatic Liver Disease by Promoting Intestinal
Anna Isaacs-Ten1, Marta Echeandia1, Mar Moreno-Gonzalez1
1Gut Microbes and Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom.
Hepatology (Baltimore, Md.)
|March 14, 2020
Summary
The gut microbiome drives liver injury in cholestatic liver disease by activating immune cells. Eliminating the microbiome prevents liver damage, highlighting its critical role in disease progression.
Area of Science:
- Hepatology
- Immunology
- Microbiome Research
Background:
- Cholestatic liver disease is linked to microbiome alterations.
- The microbiome's role in cholestasis pathogenesis is unclear.
Purpose of the Study:
- Investigate the microbiome's role in cholestatic liver injury.
- Elucidate mechanisms of microbiome-mediated liver damage.
Main Methods:
- Induced cholestasis in germ-free and conventionalized mice.
- Depleted macrophages and inhibited inflammasome activation.
- Performed in vitro studies on hepatocyte death.
Main Results:
- Liver injury from cholestasis requires the microbiome.
- Endotoxin sensitizes hepatocytes to bile acid-induced death.
- Activated macrophages increase intestinal permeability and endotoxin flux.
Conclusions:
- The intestinal microbiome promotes cholestasis-induced liver cell death and inflammation.
- Inflammasome activation in macrophages is a key mechanism.
