J Neurogastroenterol Motil.  2022 Oct;28(4):517-530. 10.5056/jnm22100.

Inflammation and Impaired Gut Physiology in Post-operative Ileus: Mechanisms and the Treatment Options

• Hussain Z
• Park H

• KMID: 2534311
• DOI: http://doi.org/10.5056/jnm22100

Abstract

Post-operative ileus (POI) is the transient cessation of coordinated gastrointestinal motility after abdominal surgical intervention. It decreases quality of life, prolongs length of hospital stay, and increases socioeconomic costs. The mechanism of POI is complex and multifactorial, and has been broadly categorized into neurogenic and inflammatory phase. Neurogenic phase mediated release of corticotropin-releasing factor (CRF) plays a central role in neuroinflammation, and affects both central autonomic response as well hypothalamic-pituitary-adrenal (HPA) axis. HPA-stress axis associated cortisol release adversely affects gut microbiota and permeability. Peripheral CRF ( p CRF) is a key player in stress induced gastric emptying and colonic transit. It functions as a local effector and interacts with the CRF receptors on the mast cell to release chemical mediators of inflammation. Mast cells proteases disrupt epithelial barrier via protease activated receptor-2 (PAR-2). PAR-2 facilitates cytoskeleton contraction to reorient tight junction proteins such as occludin, claudins, junctional adhesion molecule, and zonula occludens-1 to open epithelial barrier junctions. Barrier opening affects the selectivity, and hence permeation of luminal antigens and solutes in the gastrointestinal tract. Translocation of luminal antigens perturbs mucosal immune system to further exacerbate inflammation. Stress induced dysbiosis and decrease in production of short chain fatty acids add to the inflammatory response and barrier disintegration. This review discusses potential mechanisms and factors involved in the pathophysiology of POI with special reference to inflammation and interlinked events such as epithelial barrier dysfunction and dysbiosis. Based on this review, we recommend CRF, mast cells, macrophages, and microbiota could be targeted concurrently for efficient POI management.

Keyword

Ileus; Inflammation mediators; Macrophages; Mast cells; Permeability