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The abuse of antibiotics is creating a public health crisis and leads to the emergence of drug-resistant bacteria. Short-chain fatty acids (SCFAs) are the ferment products of gut microbiota with carbohydrate and play a pivotal role in host health. To date, there is very limited research on the potential anti-infection effect of SCFAs. In this study, the effects of butyrate on the pathogenicity of Aeromonas hydrophila (A. hydrophila) were investigated. Butyrate at sub-MIC concentrations could reduce the population growth rate of A. hydrophila but did not significantly affect its population at the stationary phase. Butyrate could decrease the production of virulence factors of A. hydrophila in a concentration-dependent manner. Sub-MIC butyrate could inhibit the activity of protease and haemolysin by 62.41% and 56.02% at 1.00 mg ml −1 , respectively, and decrease the biofilm formation of A. hydrophila at 34.71%. In vivo study showed that the sub-MIC butyrate could increase the survival of Caenorhabditis elegans (C. elegans) against A. hydrophila. Furthermore, after challenging with A. hydrophila, the survival rate of zebrafish in butyrate-supplemented group was significantly higher than that of control (p < .05). These results suggested that butyrate could be used as a promising feed additive to protect the host against A. hydrophila infection.

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