Vitamins and their roles in GC receptor function and gut homeostasis
| Vitamin | Impact on GR function | Impact on epithelial barrier integrity | Impact on microbiome composition | Antioxidant activity | Anti-inflammatory effects | Immune modulation |
|---|---|---|---|---|---|---|
| Vitamin D | Augments GR signaling by reducing local inflammation and enhancing local GC pathways [64]. | Regulates tight junction proteins (e.g., ZO-1, claudins), reducing permeability and bacterial translocation [65, 66]. | Shapes gut microbiota by promoting beneficial genera (e.g., Akkermansia, Bifidobacterium) and mitigating dysbiosis [87, 88]. | Limited direct antioxidant effects | Suppresses pro-inflammatory Th1/Th17 cells, enhances Tregs, and induces antimicrobial peptides [65, 88] | Balances adaptive immunity by supporting regulatory T cells and controlling excessive inflammation [66] |
| Vitamin C | Preserves GR function by alleviating oxidative stress, which sustains GR sensitivity [68]. | Upregulates tight junction proteins (some evidence of synergy with vitamin D3), improving barrier integrity [67]. | May help shift gut microbiota toward beneficial species; can increase short-chain fatty acid-producing bacteria. | Strong antioxidant, neutralizes ROS [64, 68] | Modulates cytokines (IL-22, IL-6) to curb inflammation; aids epithelial repair [68, 69] | Enhances phagocytic cell function (chemotaxis, phagocytosis) and supports B-cell/T-cell proliferation [69] |
| Vitamin A | Deficiency alters GR binding capacity; retinoic acid normalizes receptor activity [89]. | Enhances tight junction expression; counters barrier disruption caused by inflammatory stimuli [87]. | Regulates microbial complexity and supports mucosal immunity for gut homeostasis. | Primarily immunoregulatory, with some antioxidant benefits (especially from carotenoid forms) | Reduces inflammatory mediators and promotes epithelial repair [87, 89] | Directs T-cell homing to gut, facilitates IgA production, and aids dendritic cell function [90] |
| Vitamin E | Indirectly supports GR-mediated anti-inflammatory pathways by lowering oxidative/inflammatory loads. | Stabilizes tight junction proteins and reduces colitis-associated epithelial injury [91]. | Modulates gut microbiota composition, diminishing pro-inflammatory taxa*. | Antioxidant; lowers ROS levels | Decreases TNF-α, IL-6, and other inflammatory mediators [91] | Contributes to mucosal healing by preserving barrier integrity |
ZO-1: zonula occludens-1; GR: glucocorticoid receptor; ROS: reactive oxygen species; TNF-α: tumor necrosis factor-alpha; IL: interleukin; Treg: regulatory T cell; GC: glucocorticoid; IgA: immunoglobulin A; Th: T helper. * Pro-inflammatory taxa refer to groups of gut microbes known to promote inflammation in the body (e.g., certain Proteobacteria or Enterobacteriaceae)
