The Impact of Chronic Antibiotics Exposure on the Gut Microbiome Dysbiosis and Mucosal Barrier-Related Pathogen Susceptibility in Zebrafish Model

Abstract The symbiotic community of microorganisms in the gut plays an important role in the health of the host. While many previous studies have been performed on the interaction between the gut microbiome and the host in mammals, studies in fish are still lacking. In this study, we investigated changes in the intestinal microbiome and pathogen susceptibility of zebrafish (Danio rerio) following chronic antibiotics exposure. The chronic antibiotics exposure assay was performed on zebrafish for 30 days using oxytetracycline (Otc), sulfamethoxazole/trimethoprim (Smx/Tmp), and erythromycin (Ery), which are antibiotics widely used in aquaculture industry. The microbiome analysis indicated that Fusobacteria, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in the gut microbiome of zebrafish used in this study. However, in Smx/Tmp-treated zebrafish, the composition of Fusobacteria and Proteobacteria were changed significantly, and in Ery-treated zebrafish, the composition of Proteobacteria and Firmicutes were altered significantly. Although alpha diversity analysis showed that there was no significant difference in the richness, beta diversity analysis revealed a community imbalance in the gut microbiome of all chronically antibiotics exposed zebrafish. Intriguingly, in zebrafish with dysbiosis on the gut microbiome, the pathogen susceptibility to Edwardsiella piscicida, a representative Gram-negative fish pathogen, was reduced. Due to the further effect of gut microbiome dysbiosis, the number of goblet cells in the intestinal tissue was increased, and the intestinal mucosal barrier-related genes expression was also upregulated. In addition, as the innate immunity was enhanced by the increased mucosal barrier, the immune, stress-related gene expression in the intestinal tissue was downregulated. In this study, we provide new insight into the effect of gut microbiome dysbiosis on pathogen susceptibility.