Abstract
Commensal gut microbiota protects the immune defense of extra-intestinal organs. Gut microbiota depletion by antibiotics can impair host antiviral immune responses and alter hepatitis B virus (HBV) infection outcomes. However, how gut microbiota modulates antiviral immune response in the liver remains unclear. Here, mice were treated with broad-spectrum antibiotics to deplete gut microbiota. Gut integrity was evaluated, and translocation of live commensal gut bacteria and their components into the liver was investigated. An HBV infection model was established to evaluate impairment of antiviral immune response in the liver after gut microbiota depletion. We found that gut microbiota depletion was associated with impairment of colon epithelial integrity, and live commensal gut microbiota could translocate to the liver. Further, T cell antiviral function in the liver was impaired, partially relying on enhanced PD-1 expression, and HBV immune clearance was hampered. In conclusion, gut microbiota depletion by antibiotics can impair gut barrier function and suppress T cell antiviral immune response in the liver.
Highlights
The gut and liver closely interact with each other via the portal vein, biliary system, and systemic circulation, and both organs have significant physiological crosstalk, referred to as the gut-liver axis
broad-spectrum antibiotics (ABX) treatment inhibited the expression of the tight junction protein, zonula occludens-1 (ZO-1), and the molecules related to barrier function, including Axin2, Claudin-2, and Claudin-3 (Figure 2C)
We used broad-spectrum antibiotics to deplete the gut microbiota in mice and found that: 1) gut microbiota depletion induced by ABX is associated with damage of colon epithelial integrity; 2) live commensal gut microbiota can translocate to the liver; 3) gut microbiota depletion induced by ABX treatment can lead to impaired T cell function in the liver and hamper the immune clearance of Hepatitis B virus (HBV) infection; and 4) impaired T cell function in the liver partially relies on enhanced PD-1 expression
Summary
The gut and liver closely interact with each other via the portal vein, biliary system, and systemic circulation, and both organs have significant physiological crosstalk, referred to as the gut-liver axis. Products/toxins and metabolites from bacteria in the gut enter the liver and metabolize/detoxicate in the liver. Many bioactive mediators, including primary bile acids, are synthesized in the liver and are transported to the intestine, influencing gut function. Gut Microbiota Affects HBV Immunity indicates that the metabolites of the gut microbiota can affect immune response in the liver, and the gut-liver axis is considered pivotal in the progression of most liver diseases, including viral hepatitis, alcoholic and non-alcoholic fatty liver disease, autoimmune liver disease, liver cirrhosis, and hepatocellular carcinoma [1]. Liver diseases can affect commensal bacterial community and gut function. Hepatitis B virus (HBV) infection can alter gut microbiota composition and modulate the immune molecular expression in the intestine [2]
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