“Sugar-free” trap: Artificial sweetener acesulfame induced anxiety-like behavior in Sebastes schlegelii via disturbing bidirectional microbiota–neurotransmitter interactions

The artificial sweetener like acesulfame (ACE) pollution in marine environments significantly hinders the “One Health” frame achievement. However, the neurobehavioral toxicity and underlying mechanisms of ACE to marine fish remain unclear. Herein, the anxiety-like behavior and brain-gut axis regulatory mechanisms in juvenile Sebastes schlegelii were investigated by a waterborne ACE exposure experiment at the concentrations of 0.01, 1, and 10 mg L−1. ACE at environmentally-relevant concentrations (0.01 mg L−1) elicited typical anxiety-like behaviors in the fish, manifested as enhancing thigmotaxis, hyperactivity, and aggression. These behavioral abnormalities impaired the schooling cohesion and coordination, thereby potentially disrupting population-level ecological stability. ACE showed a tissue-specific bioaccumulation pattern in the order of intestine > liver > gill > brain > muscle. Specifically, the accumulation of ACE in the brain was considered a critical driver of its neurobehavioral toxicity, as it promoted dopamine synthesis and induced oxidative stress, thereby disrupting the excitatory–inhibitory balance within the central nervous system, ultimately triggering anxiety-like behaviors. In the intestine, ACE disrupted the mucus barrier and reshaped the microbial community by enriching pathogenic bacteria (e.g., Aeromonas spp., Pseudomonas spp.) and suppressing beneficial bacteria. Moreover, the ACE-enriched Brevundimonas and Cyanobacteria promoted dopamine synthesis, while elevated host glutathione suppressed Proteobacteria proliferation through feedback modulation of brain-gut axis. These findings demonstrated that ACE-induced anxiety-like behaviors were mediated through the bidirectional microbiota–neurotransmitter interactions along the brain-gut axis. Our study provides new insights into the brain-gut axis impact of artificial sweetener on neurobehavioral toxicity to marine fish, and underscores that accurately assessing the environmental risks of artificial sweeteners in marine ecosystems is a prerequisite for safeguarding ocean health and ensuring sustainable fisheries under the “One Health” framework.