Interplay between inflammation, immune system and neuronal pathways: effect on gastrointestinal motility

Area of Science:

• Gastroenterology
• Immunology
• Critical Care Medicine

Background:

• Sepsis is a leading cause of death in critically ill patients, primarily due to multiple organ failure.
• The gastrointestinal tract is central to sepsis pathogenesis via intestinal barrier dysfunction, bacterial translocation, and ileus.
• This review examines the gastrointestinal tract's role in sepsis, focusing on mediators, cell types, and signaling pathways.

Discussion:

• The gut wall involves complex interactions between immune cells (mast cells, macrophages), glial cells, neurons, and smooth muscle cells.
• Intracellular signaling pathways, Toll-like receptors, and neuroactive substances mediate these interactions.
• Bidirectional signaling between the gut, spinal cord, and central nervous system influences inflammation and its systemic consequences.

Key Insights:

• Intestinal barrier dysfunction, bacterial translocation, and ileus are critical in sepsis-induced organ failure.
• A complex cellular and molecular network within the gut wall orchestrates the inflammatory response.
• Gut-brain axis communication significantly impacts sepsis progression and outcomes.

Outlook:

• Novel therapies should target both gut inflammation and gastrointestinal dysfunction (motility, sensitivity, pain).
• Strategies include modulating afferent neuronal signaling and activating the vagal anti-inflammatory pathway.
• Pharmacological agents like ghrelin agonists and endocannabinoid system modulators show therapeutic potential.