Altered gut microbial networks and metabolic homeostasis in grass carp exposed to Microcystis aeruginosa

Environmental proliferation of Microcystis aeruginosa poses a significant toxicological threat to farmed fish. This study investigated the intestinal toxicity of M. aeruginosa in grass carp using integrated histological, biochemical, molecular, microbiome, and metabolomic analyses. Histological observations revealed epithelial disorganization, villus shortening, crypt hyperplasia, and goblet cell depletion. High-throughput sequencing showed stable microbial α-diversity but pronounced community restructuring, characterized by enrichment of Actinobacteria and Epsilonbacteraeota and emergence of key taxa including Prevotellaceae_UCG.001, Escherichia-Shigella, Enterobacter, and Vibrio. Oxidative imbalance was evident, accompanied by increased lipid peroxidation and reduced digestive capacity. Intestinal inflammation, epithelial barrier disruption, and mitochondrial-dependent apoptosis were markedly induced. Metabolomic profiling demonstrated clear exposure-associated metabolic reprogramming with coordinated alterations in amino acid and lipid metabolism, including activation of lysine degradation and fatty acid biosynthesis and suppression of arginine-related pathways and mTOR signaling. Microbiota-metabolite correlation analysis revealed coordinated associations between bacterial taxa and metabolic signatures. In vitro assays further confirmed reduced cell viability and antioxidant capacity in primary intestinal cells. Collectively, M. aeruginosa disrupts intestinal homeostasis in grass carp through integrated oxidative, inflammatory, apoptotic, and microbiota-associated metabolic pathways.