Table 1 Mechanisms of vitamin D and gut microbiota interaction

Regulation of tight junction proteins

Enhances expression of proteins like occludin, claudin, and zonula occludens-1

Maintains epithelial barrier integrity by reducing permeability

Protects against leaky gut syndrome and systemic inflammation

[36, 115, 116]

Modulation of immune response

Shifts immune response toward anti-inflammatory pathways (e.g., IL-10 production)

Produces SCFAs to enhance Treg differentiation and reduce inflammation

Mitigates chronic inflammation and autoimmunity

[19, 37, 117]

Promotion of beneficial microbes

Selectively enhances growth of bacteria like Akkermansia muciniphila and Bacteroides

Produces metabolites that increase VDR expression and activity

Strengthens gut-immune homeostasis, reduces risk of dysbiosis

[42, 43, 50]

Hydroxylation of vitamin D

Provides substrate for microbial hydroxylation processes (e.g., 1α and 25-hydroxylation)

Microbial enzymes contribute to activation and recycling of vitamin D

Supports vitamin D metabolism and bioavailability

[52,53,54]

Suppression of pathogenic microbes

Reduces colonization of pathogens by improving mucosal defenses

Competes with pathogens and suppresses their virulence via SCFA production

Protects against gut infections and inflammation

[21, 36, 62]

Regulation of cytokine production

Balances pro- and anti-inflammatory cytokines (reduces TNF-α, IL-6; enhances IL-10)

Microbial metabolites modulate immune signaling pathways

Prevents overactive immune responses, supports immune tolerance

[37, 116, 117]

Metabolic cross-talk

Enhances gut microbial metabolism via improved substrate availability (e.g., SCFA synthesis)

Fermentation products promote VDR expression and immune modulation

Enhances gut-immune signaling, reduces inflammageing

[37, 38, 97]

Impact on gut microbial composition

Alters phylum-level abundance (e.g., increases Bacteroidetes/Firmicutes ratio)

Adjusts microbial diversity in response to vitamin D availability

Restores microbial balance, reduces dysbiosis

[38, 41, 50]