Homeostasis of the intestinal microbiota is crucial to the health of the host, and pathogen invasion often results in dynamic changes in the composition, structure, and functions of gut microbes. Vibrio parahaemolyticus is an important opportunistic pathogen of Pacific white shrimp (Penaeus vannamei) often leading to high mortality. The V. parahaemolyticus strain that causes acute hepatopancreatic necrosis disease (AHPND) expresses the virulence genes, pirA and pirB. However, some non-AHPND strains of V. parahaemolyticus that do not carry pir genes can still cause disease in shrimp resulting in huge economic losses. The TJA114 strain of V. parahaemolyticus, which was isolated from diseased shrimp, showed strong pathogenicity toward P. vannamei and was found to lack the pir gene. This study investigated the alteration in bacterial community composition and function of intestinal microbiota in P. vannamei following infection with V. parahaemolyticus TJA114. We used 16S rRNA high-throughput sequencing and liquid chromatography with tandem mass spectrometry technologies to identify the altered bacterial taxa involved in disease in experimentally infected shrimp. These included the potentially pathogenic Oceanospirillum, Lewinella, and Saprospira and the potentially beneficial Agarivorans, Ferrimonas, and Shewanella. The alteration in composition of these bacterial taxa was closely associated with some differentially expressed metabolites identified by shrimp fecal metabolome analysis. These metabolites were mainly involved in level 3 KEGG pathways including lysine, arginine, primary and secondary bile acid biosynthesis, and purine, pyrimidine, glycerophospholipid, glycan, proline, and histidine metabolism. The findings of this study provide novel insights into the pathogenesis of vibriosis in P. vannamei caused by infection with the non-AHPND V. parahaemolyticus.