Functions of GCs in maintaining gut homeostasis
| Function category | Description | Key mechanisms/examples |
|---|---|---|
| Anti-inflammatory and antioxidant effects | Suppression of inflammatory responses and attenuation of oxidative stress to alleviate gut inflammation, protect against tissue injury, and preserve cellular viability. | - Inhibition of pro-inflammatory cytokines (e.g., IL-1β, IL-6) and induction of anti-inflammatory mediators IL-10 and Annexin A1 [64]- Upregulation of antioxidant enzymes superoxide dismutase and catalase [23, 79] |
| Preservation of epithelial barrier integrity | GRs are widely distributed throughout the GI tract [80]. GC-GR signaling strengthen gut epithelial function by enhancing epithelial tight junction structure and function to prevent pathogen invasion and maintain nutrient absorption. | - Upregulation of tight junction proteins (e.g., occludin, claudins, ZO-1) [71]- Annexin A1 as a crucial mediator for maintaining epithelial integrity [22]- Modulation of chemokine expression and control of leukocyte recruitment, resulting in decrease in gut permeability [17]- Promotion of epithelial cell regeneration |
| Modulation of microbiota composition | Support microbial diversity and homeostasis to maintain gut integrity and modulate immune responses. | - Promotion of beneficial bacterial growth [81]- Inhibition of pathogenic microbial species- Restoration of microbial balance post-dysbiosis |
| Immune system regulation | Balances immune activity to defend against pathogens while preventing excessive inflammation. | - Regulation of chemokines and leukocyte recruitment 18- Modulation of antigen presentation- Maintenance of immune tolerance |
| Interaction with the gut-brain-axis | Facilitates bidirectional interactions between the gut and the brain, impacting stress responses and neuroimmune functions [42]. | - Endothelial GRα helps regulate vascular homeostasis and supports blood-brain barrier (BBB) integrity [82]- Control of neuroinflammation, enhancing neuronal recovery, and bolstering stress resilience [46] |
| Cross-talk with lung and other organs | Support bidirectional interactions between the gut and lung which share microbial sources [50].Compromised gut barrier integrity allows microbial translocation to the lungs [51]. | - Modulation of the lung-gut axis in conditions such as asthma and inflammatory bowel disease (IBD)- GCs suppress systemic inflammatory cascades, reduce lung inflammation caused by gut-derived endotoxemia, and enhance barrier integrity in both the intestine and lungs |
| Regulation of intestinal enzymes and metabolic pathways | Control enzyme expression involved in digestion and nutrient absorption, and metabolic processes within the gut, including the conversion of amino acids into essential metabolites.Enhance glucose uptake by upregulating genes involved in glucose transport leading to increased blood glucose levels. | - Regulation of digestive enzyme expression and amino acid metabolism (e.g., arginase, glutaminase) [60]- Modulation of fucosyltransferases (FUTs) for fucosylatio- Influence on microbial metabolic pathways [31]- Upregulation of sodium-coupled glucose transporter 1 (SGLT1) in enterocytes [83] |
| Influence on gut motility and secretion | Modulation of intestinal motility and secretion of mucus and other substances essential for digestion and barrier function. Also regulate electrolyte and fluid secretion in the intestine. | - Enhance cholinergic neuromuscular transmission within the ENS [62]- Stabilize mucosal barrier [84]- Increase the electrical potential difference and Na+/K+- ATPase activity—key processes for effective ion transport [63]- Control of electrolyte and fluid secretion in the gut |
| Intestinal epithelial cells synthesis of GCs | Regulate immune responses against viruses and chronic inflammatory conditions, including macrophage activation in infections such as Helicobacter pylori. | - Regulation immune responses against viruses and chronic inflammatory conditions [17, 85, 86]- Macrophage activation for immune responses against infections like Helicobacter pylori [21] |
