Exposure to organophosphorus (OP) compounds can induce transient cognitive, neurological, and somatic symptoms that may persist over time. OP poisoning mostly occurs from pesticides used in developing countries; however, several OP nerve agent (NA) events have been reported in the last decade. OP toxicity is based on cholinesterase inhibition, which leads to varying degrees of neurotoxicity. According to clinical reports, asymptomatic victims of OP exposure may experience long-term neurological sequelae. Given the continuous communication between the nervous and enteric systems, evaluating the neurotoxic effects of OP exposure on the gut-brain axis is important. A male Swiss mouse model was employed to investigate the short- and long-term consequences of acute exposure to a sublethal dose of VX at 0.5 LD50. The investigation focused on alterations in the inflammatory system and the endocrine system, with particular attention to the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, the study encompassed an evaluation of the intestinal barrier structural and functional integrity and gut microbiota composition. A longitudinal behavioral study was also conducted to assess cognitive and emotional functions. Our results indicate that sublethal exposure to a VX disrupts the HPA axis and the intestinal homeostasis as evidenced by local inflammation, structural changes and gut microbiota shifts. Our data also indicate long-term neurological deficits as well as long-term neuroendocrine and metabolic effects suggesting a systemic homeostatic disorder. These findings highlight the necessity for comprehensive care for individuals exposed to NA and underscore the importance of identifying biomarkers for low-dose to sublethal exposure to facilitate early diagnosis and the development of effective treatments.
Gut-Brain Axis