Key components and functions of the intestinal barrier
| Component | Description | Function | Clinical implications |
|---|---|---|---|
| Epithelial layer [1, 9, 14, 71, 72] | A single layer of tightly joined intestinal epithelial cells connected by tight junctions (TJs) | - Acts as a physical barrier preventing translocation of pathogens and toxins.- Regulates nutrient and water absorption.- Maintains paracellular permeability. | - Increased permeability contributes to inflammation, IBD, and systemic conditions.- Critical in maintaining barrier integrity during sepsis and ARDS. |
| Mucus layer [73, 74] | Composed of mucins, AMPs, and IgA | - Traps pathogens and toxins.- Neutralizes microbes.- Facilitates intestinal content movement. | - Impaired mucus production increases infection and inflammation risks. |
| Enteric nervous system [75–77] | A network of neurons and glial cells regulating motility, secretion, and local immune responses | - Coordinates digestion and nutrient absorption.- Supports blood flow and barrier integrity.- Modulates inflammation and immune responses. | - ENS dysfunction impairs gut motility and barrier integrity, worsening systemic inflammation and organ dysfunction during critical illness. |
| Enteric glial cells [2, 3] | Enteric glial cells, previously considered passive support cells, are critical regulators of intestinal motility, vascular tone, and gut homeostasis | - Coordinate neuron communication involving nitric oxide (NO) and glutamate.- Support mucosal barrier integrity, regulate neuroeffector junctions. | - Dysfunction disrupts motility, vascular regulation, and barrier integrity.- Exacerbates intestinal and systemic inflammation. |
| Blood circulation [78] | Delivers nutrients and oxygen, removes waste | - Maintains epithelial integrity.- Facilitates nutrient transport into systemic circulation. | - Hypoperfusion weakens barrier function, increasing permeability and systemic inflammation. |
| Lymphatic vessels [78] | Transports fats and immune cells | - Facilitates nutrient absorption.- Filters lymph and supports immune responses. | - Dysfunction impairs nutrient absorption and immune surveillance, raising infection risk. |
| Immune cells [4] | Immune cells in the gut mucosa | - Protect against pathogens.- Maintain immune tolerance and regulate inflammation. | - Dysregulation causes excessive inflammation, contributing to IBD. |
| AMPs | Small proteins in the mucus layer [73] | - Neutralize pathogens and toxins.- Link innate and adaptive immunity via chemokine and Toll-like receptor modulation [74]. | - Impaired AMP activity compromises barrier defenses and increases infection risks. |
| Resident gut microbiota [7] | The community of microorganisms in the intestinal tract | - Competes with pathogens, aids in digestion, produces CFAs and nutrients.- Regulates lipid metabolism and immune responses. | - Dysbiosis increases inflammation, pathogen overgrowth, and susceptibility to infections, especially during critical illness. |
| Disruption of the intestinal bassier in critical illness [8, 10] | Hyperinflammatory states disrupt barrier components [9] | - Disrupts TJs, reduces mucus production, and impairs epithelial function.- Facilitates bacterial translocation and systemic inflammation [11–13]. | - Worsens MODS and nosocomial infections.- ICU interventions like antimicrobials exacerbate dysbiosis, prolonging recovery. |
ARDS: acute respiratory distress syndrome; ENS: enteric nervous system; IgA: immunoglobulin A; MODS: multiple organ dysfunction syndrome; ZO: zonula occludens; AMPs: antimicrobial peptides; IBD: inflammatory bowel disease; ICU: intensive care unit
