Probiotics and their metabolite spermidine enhance IFN-γ+CD4+ T cell immunity to inhibit hepatitis B virus
Tixiao Wang, Yu‐Chen Fan, Siyu Tan, Zehua Wang, Mengzhen Li, Xiaowei Guo, Xiangguo Yu, Qinghai Lin, Xiaojia Song, Leiqi Xu, Lixiang Li, Shiyang Li, Lifen Gao, Xiaohong Liang, Chunyang Li, 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. • Probiotics promote HBV clearance by producing spermidine • Probiotics and spermidine enhance IFN-γ + CD4 + T cell function through autophagy • Probiotics induce the decline of serum HBsAg in patients with low HBsAg levels Commensal microbes are promising in the functional cure of HBV infection. Wang et al. demonstrate that probiotics and their metabolite spermidine effectively promote the decline of HBsAg and inhibit HBV replication via autophagy-enhanced IFN-γ + CD4 + T cell immunity, highlighting the therapeutic potential of probiotics and spermidine for the functional cure of HBV patients.