• Almeida, J.I., Tenreiro, M.F., Martinez-Santamaria, L., Guerrero-Aspizua, S., Gisbert, J.P., Alves, P.M., Serra, M., Baptista, P.M., 2022. Hallmarks of the human intestinal microbiome on liver maturation and function. J. Hepatol. 76, 694–725.

  • Anthony, W.E., Wang, B., Sukhum, K.V., D'Souza, A.W., Hink, T., Cass, C., Seiler, S., Reske, K.A., Coon, C., Dubberke, E.R., Burnham, C.D., Dantas, G., Kwon, J.H., 2022.Acute and persistent effects of commonly used antibiotics on the gut microbiome and resistome in healthy adults. Cell Rep. 39, 110649.

  • Bertoletti, A., Ferrari, C., 2016. Adaptive immunity in HBV infection. J. Hepatol. 64, S71–S83.

  • Bolyen, E., Rideout, J.R., Dillon, M.R., Bokulich, N.A., Abnet, C.C., AL-Ghalith, G.A., Alexander, H., Alm, E.J., Arumugam, M., Asnicar, F., Bai, Y., Bisanz, J.E., Bittinger, K., Brejnrod, A., Brislawn, C.J., Brown, C.T., Callahan, B.J., CaraballoRodriguez, A.M., Chase, J., Cope, E.K., Da Silva, R., Diener, C., Dorrestein, P.C., Douglas, G.M., Durall, D.M., Duvallet, C., Edwardson, C.F., Ernst, M., Estaki, M., Fouquier, J., Gauglitz, J.M., Gibbons, S.M., Gibson, D.L., Gonzalez, A., Gorlick, K., Guo, J., Hillmann, B., Holmes, S., Holste, H., Huttenhower, C., Huttley, G.A., Janssen, S., Jarmusch, A.K., Jiang, L., Kaehler, B.D., Kang, K.B., Keefe, C.R., Keim, P., Kelley, S.T., Knights, D., Koester, I., Kosciolek, T., Kreps, J., Langille, M.G.I., Lee, J., Ley, R., Liu, Y.X., Loftfield, E., Lozupone, C., Maher, M., Marotz, C., Martin, B.D., Mcdonald, D., Mciver, L.J., Melnik, A.V., Metcalf, J.L., Morgan, S.C., Morton, J.T., Naimey, A.T., Navas-Molina, J.A., Nothias, L.F., Orchanian, S.B., Pearson, T., Peoples, S.L., Petras, D., Preuss, M.L., Pruesse, E., Rasmussen, L.B., Rivers, A., Robeson, M.S., 2Nd, Rosenthal, P., Segata, N., Shaffer, M., Shiffer, A., Sinha, R., Song, S.J., Spear, J.R., Swafford, A.D., Thompson, L.R., Torres, P.J., Trinh, P., Tripathi, A., Turnbaugh, P.J., Ul-Hasan, S., Van der Hooft, J.J.J., Vargas, F., VazquezBaeza, Y., Vogtmann, E., Von Hippel, M., Walters, W., et al., 2019. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat.Biotechnol. 37, 852–857.

  • Chou, H.H., Chien, W.H., Wu, L.L., Cheng, C.H., Chung, C.H., Horng, J.H., Ni, Y.H., Tseng, H.T., Wu, D., Lu, X., Wang, H.Y., Chen, P.J., Chen, D.S., 2015. Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota. Proc. Natl. Acad. Sci. U. S. A. 112, 2175–2180.

  • Croswell, A., Amir, E., Teggatz, P., Barman, M., Salzman, N.H., 2009. Prolonged impact of antibiotics on intestinal microbial ecology and susceptibility to enteric Salmonella infection. Infect. Immun. 77, 2741–2753.

  • Dion, S., Bourgine, M., Godon, O., Levillayer, F., Michel, M.L., 2013. Adeno-associated virus-mediated gene transfer leads to persistent hepatitis B virus replication in mice expressing HLA-A2 and HLA-DR1 molecules. J. Virol. 87, 5554–5563.

  • Drummond, R.A., Desai, J.V., Ricotta, E.E., Swamydas, M., Deming, C., Conlan, S., Quinones, M., Matei-Rascu, V., Sherif, L., Lecky, D., Lee, C.R., Green, N.M., Collins, N., Zelazny, A.M., Prevots, D.R., Bending, D., Withers, D., Belkaid, Y., Segre, J.A., Lionakis, M.S., 2022. Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria. Cell Host Microbe 30, 1020–1033.e6.

  • Du, Y., Broering, R., Li, X., Zhang, X., Liu, J., Yang, D., Lu, M., 2021. In vivo mouse models for hepatitis B virus infection and their application. Front. Immunol. 12, 766534.

  • Durack, J., Lynch, S.V., 2019. The gut microbiome: relationships with disease and opportunities for therapy. J. Exp. Med. 216, 20–40.

  • Erttmann, S.F., Swacha, P., Aung, K.M., Brindefalk, B., Jiang, H., Hartlova, A., Uhlin, B.E., Wai, S.N., Gekara, N.O., 2022. The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis. Immunity 55, 847–861.e10.

  • Fink, A.L., Engle, K., Ursin, R.L., Tang, W.Y., Klein, S.L., 2018. Biological sex affects vaccine efficacy and protection against influenza in mice. Proc. Natl. Acad. Sci. U. S.A. 115, 12477–12482.

  • Fox, J.G., Feng, Y., Theve, E.J., Raczynski, A.R., Fiala, J.L., Doernte, A.L., Williams, M., Mcfaline, J.L., Essigmann, J.M., Schauer, D.B., Tannenbaum, S.R., Dedon, P.C., Weinman, S.A., Lemon, S.M., Fry, R.C., Rogers, A.B., 2010. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut 59, 88–97.

  • Ganem, D., 2004. Hepatitis B virus infection - Natural history and clinical consequences(vol 350, pg 1118, 2004). N. Engl. J. Med. 351, 1268, 1268.

  • Guo, W., Zhou, X., Li, X., Zhu, Q., Peng, J., Zhu, B., Zheng, X., Lu, Y., Yang, D., Wang, B., Wang, J., 2021. Depletion of gut microbiota impairs gut barrier function and antiviral immune defense in the liver. Front. Immunol. 12, 636803.

  • Huang, H., Ren, Z., Gao, X., Hu, X., Zhou, Y., Jiang, J., Lu, H., Yin, S., Ji, J., Zhou, L., Zheng, S., 2020. Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma. Genome Med. 12, 102.

  • Huang, L.R., Wu, H.L., Chen, P.J., Chen, D.S., 2006. An immunocompetent mouse model for the tolerance of human chronic hepatitis B virus infection. Proc. Natl. Acad. Sci.U. S. A. 103, 17862–17867.

  • Joo, E.J., Cheong, H.S., Kwon, M.J., Sohn, W., Kim, H.N., Cho, Y.K., 2021. Relationship between gut microbiome diversity and hepatitis B viral load in patients with chronic hepatitis B. Gut Pathog. 13, 65.

  • Kosinska, A.D., Pishraft-Sabet, L., Wu, W., Fang, Z., Lenart, M., Chen, J., Dietze, K.K., Wang, C., Kemper, T., Lin, Y., Yeh, S.H., Liu, J., Dittmer, U., Yuan, Z., Roggendorf, M., Lu, M., 2017. Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models. Hepatology 66, 69–83.

  • Lee, H.M., Banini, B.A., 2019. Updates on chronic HBV: current challenges and future goals. Curr. Treat. Options Gastroenterol. 17, 271–291.

  • Lucifora, J., Salvetti, A., Marniquet, X., Mailly, L., Testoni, B., Fusil, F., Inchauspe, A., Michelet, M., Michel, M.L., Levrero, M., Cortez, P., Baumert, T.F., Cosset, F.L., Challier, C., Zoulim, F., Durantel, D., 2017. Detection of the hepatitis B virus (HBV) covalently-closed-circular DNA (cccDNA) in mice transduced with a recombinant AAV-HBV vector. Antivir. Res. 145, 14–19.

  • Lynn, M.A., Eden, G., Ryan, F.J., Bensalem, J., Wang, X., Blake, S.J., Choo, J.M., Chern, Y.T., Sribnaia, A., James, J., Benson, S.C., Sandeman, L., Xie, J., Hassiotis, S., Sun, E.W., Martin, A.M., Keller, M.D., Keating, D.J., Sargeant, T.J., Proud, C.G., Wesselingh, S.L., Rogers, G.B., Lynn, D.J., 2021. The composition of the gut microbiota following early-life antibiotic exposure affects host health and longevity in later life. Cell Rep. 36, 109564.

  • Meier, A., Chang, J.J., Chan, E.S., Pollard, R.B., Sidhu, H.K., Kulkarni, S., Wen, T.F., Lindsay, R.J., Orellana, L., Mildvan, D., Bazner, S., Streeck, H., Alter, G., Lifson, J.D., Carrington, M., Bosch, R.J., Robbins, G.K., Altfeld, M., 2009. Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat.Med. 15, 955–959.

  • Morgun, A., Dzutsev, A., Dong, X., Greer, R.L., Sexton, D.J., Ravel, J., Schuster, M., Hsiao, W., Matzinger, P., Shulzhenko, N., 2015. Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks. Gut 64, 1732–1743.

  • Ren, Y.D., Ye, Z.S., Yang, L.Z., Jin, L.X., Wei, W.J., Deng, Y.Y., Chen, X.X., Xiao, C.X., Yu, X.F., Xu, H.Z., Xu, L.Z., Tang, Y.N., Zhou, F., Wang, X.L., Chen, M.Y., Chen, L.G., Hong, M.Z., Ren, J.L., Pan, J.S., 2017. Fecal microbiota transplantation induces hepatitis B virus e-antigen (HBeAg) clearance in patients with positive HBeAg after long-term antiviral therapy. Hepatology 65, 1765–1768.

  • Teng, Y., Xu, Z., Zhao, K., Zhong, Y., Wang, J., Zhao, L., Zheng, Z., Hou, W., Zhu, C., Chen, X., Protzer, U., Li, Y., Xia, Y., 2021. Novel function of SART1 in HNF4alpha transcriptional regulation contributes to its antiviral role during HBV infection.J. Hepatol. 75, 1072–1082.

  • Tian, Y., Kuo, C.F., Chen, W.L., Ou, J.H., 2012. Enhancement of hepatitis B virus replication by androgen and its receptor in mice. J. Virol. 86, 1904–1910.

  • Tripathi, A., Debelius, J., Brenner, D.A., Karin, M., Loomba, R., Schnabl, B., Knight, R., 2018. The gut-liver axis and the intersection with the microbiome. Nat. Rev.Gastroenterol. Hepatol. 15, 397–411.

  • Wang, J., Zhou, X., Li, X., Guo, W., Zhu, Q., Zhu, B., Lu, Y., Zheng, X., Yang, D., Wang, B., 2022. Fecal microbiota transplantation alters the outcome of hepatitis B virus infection in mice. Front. Cell. Infect. Microbiol. 12, 844132.

  • Wang, S.H., Yeh, S.H., Lin, W.H., Yeh, K.H., Yuan, Q., Xia, N.S., Chen, D.S., Chen, P.J., 2012. Estrogen receptor alpha represses transcription of HBV genes via interaction with hepatocyte nuclear factor 4alpha. Gastroenterology 142, 989–998.e4.

  • Wang, X., Zhu, J., Zhang, Y., Li, Y., Ma, T., Li, Q., Xu, J., Xu, L., 2018. The doses of plasmid backbone plays a major role in determining the HBV clearance in hydrodynamic injection mouse model. Virol. J. 15, 89.

  • Wargo, J.A., 2020. Modulating gut microbes. Science 369, 1302–1303.

  • Wu, T., Li, F., Chen, Y., Wei, H., Tian, Z., Sun, C., Sun, R., 2019. CD4(+) T cells play a critical role in microbiota-maintained anti-HBV immunity in a mouse model. Front.Immunol. 10, 927.

  • Xia, Y., Cheng, X., Blossey, C.K., Wisskirchen, K., Esser, K., Protzer, U., 2017. Secreted interferon-inducible factors restrict hepatitis B and C virus entry in vitro. J Immunol Res 2017, 4828936.

  • Xia, Y., Liang, T.J., 2019. Development of direct-acting antiviral and host-targeting agents for treatment of hepatitis B virus infection. Gastroenterology 156, 311–324.

  • Xu, Z., Zhao, L., Zhong, Y., Zhu, C., Zhao, K., Teng, Y., Cheng, X., Chen, Q., Xia, Y., 2022.A novel mouse model harboring hepatitis B virus covalently closed circular DNA. Cell Mol Gastroenterol Hepatol 13, 1001–1017.

  • Yan, H., Zhong, G.C., Xu, G.W., He, W.H., Jing, Z.Y., Gao, Z.C., Huang, Y., Qi, Y.H., Peng, B., Wang, H.M., Fu, L.R., Song, M., Chen, P., Gao, W.Q., Ren, B.J., Sun, Y.Y., Cai, T., Feng, X.F., Sui, J.H., Li, W.H., 2012. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 1, e00049.

  • Yang, D., Liu, L., Zhu, D., Peng, H., Su, L., Fu, Y.X., Zhang, L., 2014. A mouse model for HBV immunotolerance and immunotherapy. Cell. Mol. Immunol. 11, 71–78.

  • Yang, X.A., Lv, F., Wang, R., Chang, Y., Zhao, Y., Cui, X., Li, H., Yang, S., Li, S., Zhao, X., Mo, Z., Yang, F., 2020. Potential role of intestinal microflora in disease progression among patients with different stages of Hepatitis B. Gut Pathog. 12, 50.

  • Zarrinpar, A., Chaix, A., Xu, Z.Z., Chang, M.W., Marotz, C.A., Saghatelian, A., Knight, R., Panda, S., 2018. Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism. Nat. Commun. 9, 2872.