Every year, millions of people die from abdominal sepsis, making it a real global health emergency regardless age, ethnicity, location and access to therapeutic care. Sepsis is an uncontrolled systemic inflammation of the organism in response to pathogens invasion. Although the survival rate is significantly increased in the last years because of the improvements of hospitalization conditions and the appropriate antibiotic therapy, the full recovery is dramatically impaired by late manifestations of neurological dysfunctions and cognitive impairments, causing a permanent disability in patients. Understanding the molecular mechanism at the basis of this neurocognitive decline might guarantee a higher quality of life in association with the survival rate of the pathology. Neurocognitive impairment induced by sepsis are not completely understood, and in the last years the possible involvement of the enteric nervous system (ENS) and gut microbiota alterations following sepsis have been highlighted as primitive etiology of tardive neurological dysfunctions in septic patients. It is believed that following the migration of pathogenic bacteria from the gut lumen to the ENS, a marked immune/inflammatory response is activated by enteric glial cells (EGC) that, behaving as antigen presenting cells in the gut, significantly amplify the enteric cytokine response to the brain by a vagal connection. Altered microbiota, works thus as an immune priming of EGC, that reverberates from gut to the spinal cord hence affecting selective brain areas such as cortex and hippocampus. The present research aims at investigate thus the connection among microbiota challenge, EGC priming and tardive neurological dysfunction in the brain in a model of mice sepsis induced by cecal ligation and puncture (CLP). By molecular, micro-biomics and behavioral approaches we will aim at identify novel targets to address for future medical approaches reducing cognitive impairment due to sepsis.
