Neurotoxicity and Intestinal Microbiota Dysbiosis in the Chinese Mitten Crab (Eriocheir sinensis) Induced by Anatoxin-a: A Microbiota–Intestine–Brain Axis Perspective

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 (<i>Eriocheir sinensis</i>). 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 <i>Tyzzerella</i> and <i>Clostridium sensu stricto</i> 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.