Clarifying mechanisms underlying the selective adhesion of probiotics and competitive exclusion of pathogens in the intestine is a central theme for shrimp health. Under experimental manipulation of probiotic strain (i.e.,Lactiplantibacillus plantarumHC-2) adhesion to the shrimp mucus, this study tested the core hypothesis that homologous genes shared between probiotic and pathogen would affect the adhesion of probiotics and exclusion of pathogens by regulating the membrane proteins of probiotics. Results indicated that the reduction of FtsH protease activity, which significantly correlated with the increase of membrane proteins, could increase the adhesion ability ofL. plantarumHC-2 to the mucus. These membrane proteins mainly involved in transport (glycine betaine/carnitine/choline ABC transporterchoS, ABC transporter, ATP synthase subunit aatpB, amino acid permease) and regulation of cellular processes (histidine kinase). The genes encoding the membrane proteins were significantly (p< 0.05) up-regulated except those encoding ABC transporters and histidine kinases inL. plantarumHC-2 when co-cultured withVibrio parahaemolyticusE1, indicating that these genes could helpL. plantarumHC-2 to competitively exclude pathogens. Moreover, an arsenal of genes predicted to be involved in carbohydrate metabolism and bacteria-host interactions were identified inL. plantarumHC-2, indicating a clear strain adaption to host’s gastrointestinal tract. This study advances our mechanistic understanding of the selective adhesion of probiotics and competitive exclusion of pathogens in the intestine, and has important implications for screening and applying new probiotics for maintaining gut stability and host health.