# Microbiota-Derived Regulation of AhR and VDR Signaling in Intestinal Inflammation: Protective Roles of Prebiotics, Probiotics, and Postbiotics

## TL;DR

This paper explores how gut microbes influence intestinal inflammation through AhR and VDR signaling, and evaluates the potential of prebiotics, probiotics, and postbiotics for treatment.

## Contribution

The paper introduces three testable models for AhR–VDR axis cooperation and evaluates the therapeutic potential of microbiota-derived interventions.

## Key findings

- Indoles and SCFAs modulate intestinal immunity via AhR and VDR signaling pathways.
- Prebiotics, probiotics, and postbiotics each have distinct mechanisms and limitations in regulating inflammation.
- Postbiotics offer standardized delivery but require formulation improvements for clinical use.

## Abstract

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.