Gut dysbiosis-induced cerebral clock suppression mediates deltamethrin immunotoxicity via the brain-thyroid-immune Axis

The paradigm for understanding how environmental pollutants affect aquatic organisms is shifting from direct tissue damage to remote regulation via complex inter-system communication. However, the exact mechanisms by which widespread waterborne pesticides remotely reprogram peripheral myeloid cell-mediated antibacterial immunity remain a critical knowledge gap. In this study, Nile tilapia ( Oreochromis niloticus ) were employed to systematically investigate the cross-system immunotoxic mechanisms of deltamethrin. We discovered that prolonged deltamethrin exposure severely compromised host antibacterial immunity, characterized by suppressed myeloid cell proliferation, phagocytosis, and reactive oxygen species (ROS) production. Mechanistically, multi-omics analyses revealed a complete toxicological cascade driven through the “gut microbiota-brain rhythm-thyroid axis”. Specifically, deltamethrin exposure induced intestinal microbiota dysbiosis, characterized by the depletion of beneficial Cetobacterium and enrichment of opportunistic Leucobacter . This dysbiotic state triggered excessive activation of cerebral arachidonic acid metabolism and inflammation, which subsequently suppressed the expression of the core circadian clock gene Clock in the brain. This cerebral circadian disruption suppressed TSH secretion and impaired peripheral myeloid-cell proliferation and antibacterial activity. Fecal microbiota transplantation and pharmacological Clock inhibition reproduced TSH suppression and myeloid dysfunction, supporting causality along the microbiota– Clock –neuroendocrine–immune axis. Dietary sodium butyrate interrupted this cascade, restoring intestinal homeostasis, normalizing cerebral Clock signaling and TSH secretion, and recovering host antibacterial competence. These findings provide a systemic framework for understanding how pollutants remotely reshape host immunity and offer a theoretical basis for nutritional intervention strategies in the future.