Disruption of intestinal mucosal immunity and microbial homeostasis in Schizothorax davidi under chronic DBP exposure: From functional compensation to transcriptional decompensation.

Di-n‑butyl phthalate (DBP) is a ubiquitous environmental pollutant in the Yangtze River, yet the integrated toxicological mechanisms by which it impairs the microbiota-gut-brain axis to induce behavioral alterations in fish remain poorly understood. As a rare fish endemic to the upper reaches of the Yangtze River and a pivotal ecological indicator, Schizothorax davidi is currently facing severe environmental exposure risks. In this study, Schizothorax davidi was exposed to environmentally relevant concentrations of DBP (3, 30, and 300 μg/L) for 30days. A multidisciplinary approach, integrating YOLOv8-based behavioral tracking with multi-omics, was employed to evaluate its chronic toxicity. Our results revealed a biphasic behavioral response: acute hyperactivity at low doses (T1), acting as a stress-induced escape response, transitioned into significant locomotor suppression at higher doses (T2-T3), indicating non-adaptive neurotoxic impairment. Joint transcriptomic and 16S rRNA analysis demonstrated that the intestine shifted from a state of functional immune compensation to transcriptional decompensation as DBP concentrations increased. Furthermore, DBP exposure dramatically restructured the gut microbiota, identifying Planctomycetota as a keystone functional hub; its decline significantly correlated with the downregulation of host immune-regulatory and mucosal protective genes. In contrast to the intestinal response, transcriptomic interference in the brain intensified with concentration, triggering a TNF-mediated "molecular storm" and activating apoptotic pathways that signify a transition from reversible neuroinflammation to irreversible neural damage. Collectively, these findings demonstrate that DBP exposure compromises both the physical and microbial barriers of the gut, enabling the translocation of systemic inflammatory signals that drive central neurological failure. This research provides crucial mechanistic insights and scientific evidence for the ecological risk assessment of native fish species in the upper Yangtze River.