Tripartite Interaction of Lactiplantibacillus plantarum Y42, Tryptophan and Gut Microbiota Modulates AhR/Nrf2/NF-κB Axis for Dual Protection Against Intestinal Barrier Damage and Inflammation

The aim of this study was to investigate the effects of the supernatant from the co-culture of intestinal flora from healthy human feces, Lactiplantibacillus plantarum Y42 (L. plantarum Y42) and tryptophan on intestinal barrier function impairment and inflammatory injury in lipopolysaccharide (LPS)-induced Caco-2/RAW264.7 co-culture model. The co-culture supernatant promoted the expression of tight junction proteins (Claudin-1, Occludin, ZO-1), regulated inflammatory factors, reduced cell permeability, and alleviated the barrier function damage and inflammation of Caco-2/RAW264.7 cells exposed to LPS. The promotion of tight junction protein expression and inhibition of nuclear factor kappa-B (NF-κB) signaling pathway by the co-culture supernatant were all dependent on the activation of aromatic hydrocarbon receptor (AhR) signaling pathway. The main metabolites in the co-culture supernatant were indole-3-lactate acid (ILA), 3-indolealdehyde (IAld) and indole-3-acetic acid (IAA), which as the ligands activate AhR pathway. These findings provide support for the development of postbiotics based on L. plantarum Y42 to alleviate intestinal inflammation and restore intestinal barrier function.