Effect of microcystin-LR on intestinal microbiota, metabolism, and health of zebrafish (Danio rerio)

Microcystin-LR (MC-LR) is typically produced along with the occurrence of cyanobacterial blooms, potentially exerting deleterious effects on intestinal microbiota and health in aquatic animals. To date, the underlying mechanism by which MC-LR affects intestinal health remains elusive. In this study, adult male zebrafish were exposed to MC-LR to assess its impact on the microbiome and metabolome. Histopathological and biochemical results indicated that MC-LR damaged intestinal villi and epithelial cells, induced intestinal barrier injury and inflammatory response. Metabolomics results revealed that MC-LR induced amino acid, carbohydrate, lipid, energy metabolisms dysbiosis, and specifically promoted glycine, serine and threonine metabolism. Metagenomics results demonstrated that MC-LR altered the composition of intestinal microbiota, and microbial function prediction suggested that MC-LR promoted the functions associated with amino acid, lipid, carbohydrate and energy metabolisms. Multiomics and Metorigin analyses jointly confirmed that glycine, serine and threonine metabolism was predominantly regulated by dominant Proteobacteria, Firmicutes, Fusobacteriota and Bacteroidota under MC-LR stress. This study offers a comprehensive perspective on the toxicity of microbiota and microbiota-derived metabolism in fish intestines induced by MC-LR and deepens our comprehension of the disruptive influence of MC-LR on intestinal homeostasis in organisms.