Microbiota-derived indoles and short-chain fatty acids (SCFAs) modulate intestinal immunity via the aryl hydrocarbon receptor (AhR) and vitamin D receptor (VDR). This review proposes an operational AhR-VDR axis-three testable models (sequential, parallel, reciprocal)-to explain how indoles (AhR) and SCFAs/vitamin D (VDR) may cooperate to drive IL-22-mediated repair, antimicrobial peptide production, autophagy, and tight-junction restoration. We critically evaluate prebiotics, probiotics, and postbiotics: prebiotics shift fermentation toward SCFAs but show context-dependent effects; probiotics can supply indole-type AhR ligands yet are strain-specific; postbiotics offer standardized ligand delivery but face formulation challenges. We distinguish Salmonella-specific findings (e.g., SCFA suppression of SPI-1) from general colitis data and prioritize molecular validation, temporal mapping, multi-omics responder stratification, and standardized postbiotic development for clinical translation.
Fu-Chen Huang (Wed,) studied this question.