The gut microbiome plays an important role in the immune system of invertebrates and vertebrates. Pre- and pro-biotic dietary could improve gut microbiome and benefit to host. It has been reported that pre- or pro-biotic could enhance shrimp immune system by increasing activities of phenoloxidase (PO), prophenoloxidase (ProPO) and superoxide dismutase. During viral infection, alteration of the host immune system could influence the gut microbiome and possibly give a chance to other pathogens. In this study, intestine immune genes of STAT-silenced shrimp were investigated. During WSSV infection, expression levels of PmVago1, PmDoral and PmSpätzle in STAT silenced shrimp were increased as compared with WSSV infected shrimp. The transcription levels of antimicrobial peptides including crustinPm1, crustinPm7 and PmPEN3 were higher in WSSV challenged PmSTAT silenced shrimp, compared with that of normal shrimp infected with WSSV. Meanwhile, PmSTAT suppressed PmProPO1, PmProPO2 and PmPPAE1 expressions during WSSV infection. Moreover, microbiome of P. monodon during WSSV infection has been studied. The result revealed that the relative abundance of phyla Bacteroidetes, Actinobacteria and Planctomycetes reduced in WSSV challenged shrimp. At the species level, the abundance of P. damselae, a pathogen human and marine animals, was significantly increased in WSSV challenged shrimp.