The industrial biocide benzisothiazolinone impairs pathogen resistance in larval zebrafish by inducing microbiota dysbiosis

Benzisothiazolinone (BIT), a most widely-used isothiazolinone biocide, has been detected in water environments, posing risks to aquatic ecosystems. However, toxicological studies of BIT in aquatic organisms are still limited. This study exposed zebrafish embryos to 0, 1, 10, 100, and 1000 μg/L BIT for 14 days, and investigated the effect of BIT on the innate immune function of larval fish. 16S rRNA Sequencing revealed that BIT exposure reduced microbial diversity and richness, while increased pathogenic genera like Plesiomonas and Acinetobacter in larval fish. Then, the intestinal structure and gut barrier function were impaired, and the elevated lipopolysaccharides levels activated the Toll-like Receptor signaling pathway and triggered a pro-inflammatory innate immune response in zebrafish. The ability of zebrafish to resist pathogen Infection was further impaired, as indicated by a failed recruitment of macrophages in the intestinal area after Escherichia coli Infection. Whereas, dietary administration of probiotic Lactobacillus rhamnosus ameliorated the immunotoxicity of BIT, and restored the zebrafish larvae' immunity against pathogens. These findings elucidated the adverse effect of BIT on the innate immune function of larval zebrafish from the perspective of intestinal health and microbial disruption, and also provided insights into probiotic-based strategies for mitigating isothiazolinone biocides toxicity in aquatic organisms.

Antibacterial defense; Benzisothiazolinone; Microbiota; Probiotic; Zebrafish.