From:  Synergistic glucocorticoids, vitamins, and microbiome strategies for gut protection in critical illness

 Vitamins and their roles in GC receptor function and gut homeostasis

VitaminImpact on GR functionImpact on epithelial barrier integrityImpact on microbiome compositionAntioxidant activityAnti-inflammatory effectsImmune modulation
Vitamin DAugments 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 effectsSuppresses 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 CPreserves 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 ADeficiency 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 EIndirectly 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 levelsDecreases 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)