Dysfunction of the Gut-Brain-Axis in delayed encephalopathy after carbon monoxide poisoning

Abstract

Carbon monoxide (CO) poisoning usually causes brain lesions and delayed encephalopathy, also known as delayed neurological sequelae (DNS). The mechanism of direct brain damage caused by CO poisoning is extremely complicated which is mainly focused on the hypoxia, disorder of energy metabolism, failure of the cellular mitochondrial respiration, oxidative stress, inflammation, auto-immunological attack, excitatory amino acid toxicity, etc. However, the etiology for neurological deficits that arise from days to weeks after poisoning remains unclear. In recent years, more and more studies have shown that the intestinal flora and their gene expression products communicate directly with the brain and transmit information to each other through the complex enteric nervous system, also called Gut-Brain-Axis (GBA), and the mismatch between the metabolism and the gut microbiota is thought to be important for many neurological disorders, such as multiple sclerosis, mood and anxiety disorders, Alzheimer disease, etc. Therefore, we propose a hypothesis that CO poisoning leads to dysbiosis of the gut microbiota, affects neuroendocrine system, neuroimmnue system, autonomic system and enternic nervous system, causes disruption of symbiotic microbial populations in the gut and increases intestinal permeability, leading to “leaky out” of intestinal microorganisms and metabolites from the gut into the bloodstream, disrupts the homeostatic state of brain tissues and induces neuroinflammation, thus contributing to “persistent and worsening” brain damage and leading to the development of DNS. We believe that the combination therapies to remodel gut microbiota and regulate host metabolism may be important for the prevention and treatment of DNS after CO poisoning.