SHORT- AND LONG-TERM DISORDERS OF THE GUT-BRAIN AXIS INDUCED BY ORGANOPHOSPHATE EXPOSURE

Organophosphorus (OP) compounds are widely used as pesticides in developing countries, raising significant public health concerns. In addition, over the past decade, there has been a resurgence in the use of OP nerve agents (NOP), leading in casualties among civilian and military populations. OP inhibit cholinesterase, inducing hypercholinergia and disrupting brain homeostasis, resulting in varying degrees of neurotoxicity. The gastrointestinal system expresses numerous nicotinic receptors and is innervated by cholinergic neurons. In our previous research, we demonstrated that the intestinal tract undergoes alterations as a consequence of NOP poisoning. Furthermore, an accumulation of Soman, a highly lethal NOP, was reported in the intestinal lumen during the 24h following exposure. However, the secondary and/or peripheral consequences, such as physiological barriers, remain poorly studied. The objective of the present study was to elucidate the particular effects of NOP exposure on the intestinal barrier and its influence on the regulation of the gut-brain axis. In this study, a male Swiss mouse model was employed to investigate the short- and long-term consequences of sublethal doses of Soman (0.3/0.5 LD50). The study encompassed a comprehensive evaluation of the intestinal barrier (permeability, structural and functional integrity, gut microbiota composition). Furthermore, an examination of alterations in the immune and endocrine systems, in conjunction with behavioral changes, was undertaken to elucidate the comprehensive impact of soman exposure on biological systems. Our findings underscore the necessity to understand these mechanisms for the development of new therapeutic strategies, including for exposed but asymptomatic individuals who do not receive emergency treatment.