Abstract
Anatoxin-a (ANTX-a), a potent neurotoxin produced by various cyanobacterial species, poses a serious threat to aquatic organisms. This study investigated the neurotoxicity of ANTX-a on juvenile Chinese mitten crab (Eriocheir sinensis). Different from previous studies on vertebrate models or fish liver toxicity, we focused on the microbiota–intestine–brain axis. Results demonstrated that ANTX-a exposure induced significant neurotoxicity, marked by the upregulation of apoptosis-related genes and disruption of neurotransmitter homeostasis. Transcriptomic analysis of thoracic ganglia revealed significant dysregulation of metabolic pathways, characterized by upregulated histidine metabolism (elevated histidine decarboxylase-like) and downregulated lipid metabolism (suppressed sphingomyelin phosphodiesterase-like). Additionally, increased intestinal histamine levels and elevated serum diamine oxidase activity indicated intestinal barrier damage. Intestinal microbiota analysis revealed that the abundance of nerve-related bacteria Tyzzerella and Clostridium sensu stricto 1 changed significantly. In summary, these findings indicate that ANTX-a induced neurotoxicity by affecting neurotransmitter systems and gut health, implicating the microbiota–intestine–brain axis. The results underscore the role of microbiota–intestine–brain communication in cyanotoxin toxicity within aquatic invertebrates and provide new insights into the ecotoxicological risks of cyanobacterial blooms in aquatic invertebrates.