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Cell Reports Medicine

Cell Reports Medicine

IF: 11.7
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Probiotics and their metabolite spermidine enhance IFN-γ+CD4+ T?cell immunity to inhibit hepatitis B virus

Published:19 November 2024 DOI: 10.1016/j.xcrm.2024.101822 PMID: 39536754
Tixiao Wang, Yuchen Fan, Chunhong Ma

Abstract

The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γ+CD4+ T?cell immune response. Depletion of CD4+ T?cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition. Specifically, probiotics-derived spermidine accumulates in the gut and transports to the liver, where it exhibits a similar anti-HBV effect. Mechanistically, spermidine enhances IFN-γ+CD4+ T?cell immunity by autophagy. Strikingly, administration of probiotics in HBV patients reveals a preliminary trend to accelerate the decline of serum HBsAg. In conclusion, probiotics and their derived spermidine promote HBV clearance via autophagy-enhanced IFN-γ+CD4+ T?cell immunity, highlighting the therapeutic potential of probiotics and spermidine for the functional cure of HBV patients.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Metronidazole 443-48-1 C6H9N3O3 944 suppliers $14.00-$1188.00
Neomycin sulfate 1405-10-3 C23H48N6O17S 906 suppliers $5.00-$1865.79
Ampicillin 69-53-4 C16H19N3O4S 602 suppliers $13.00-$499.00
Entecavir 142217-69-4 C12H15N5O3 555 suppliers $15.00-$4277.00
Vancomycin 1404-90-6 C66H75Cl2N9O24 322 suppliers Inquiry
FLUORESCEIN ISOTHIOCYANATE-DEXTRAN 60842-46-8 C11H12N2S.HCl 182 suppliers $46.00-$2180.00

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