Environmentally relevant 6PPD-quinone drives personality-specific behavioral abnormalities in juvenile grouper through interplay between neuroinflammation and gut microbial dysbiosis.

Abstract

The lethal impacts of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), a transformation product of tire wear antioxidant 6PPD, on salmonids pose great threats to "Ocean Health" within One Health frame. However, its sublethal effects on non-sensitive fish, especially the behaviors and the underlying mechanisms, remain poorly understood. Therefore, juvenile pearl gentian grouper (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatus), one of the ecologically and economically important marine species, was selected to compare the effects of 6PPD-Q and 6PPD at an environmentally relevant concentration (10 µg L) on the personality behaviors and brain-gut axis regulation mechanism. After 30 days of exposure, 6PPD-Q significantly reduced the time spent in the thigmotaxis zone and locomotor activity by 19.40% and 14.03%, respectively, while 6PPD showed little effect, indicating that 6PPD-Q increased risk-taking propensity and decreased activity, thereby disrupting personality behavioral homeostasis in the non-sensitive fish. Mechanistically, 6PPD-Q exposure mediated the neurotoxic effects through inducing persistent neuroinflammatory responses, increasing blood-brain barrier permeability, and decreasing neuronal activity. These neurotoxic effects were associated with the downregulated DNA damage repair gene (gadd45ba) and anti-inflammatory regulator (dusp1). In parallel, 6PPD-Q impaired intestinal physicochemical barrier integrity, reduced beneficial bacteria (e.g., Muribaculaceae) and enriched pathogenic bacteria (e.g., Nautella), thereby disturbing gut microbial homeostasis and brain-gut axis regulation. From "brain-gut" axis perspective, this study elucidated the mechanisms by which 6PPD-Q at environmentally relevant concentration disrupts personality behavioral balance in non-sensitive marine fish, providing new insight for ecological risk assessment and early warning of emerging tire-derived contaminants in marine ecosystems.