ABSTRACT Impairment of intestinal barrier function is intricately linked to intestinal inflammation. Emerging evidence highlights that tryptophan‐derived metabolites from the intestinal microbiota play a crucial role in maintaining the homeostasis of intestinal barrier function. In this study, a Caco‐2/HT29 co‐culture model was applied to evaluate the effects of indole‐3‐acetic acid (IAA) on the intestinal barrier and explore its underlying mechanism of action. Results demonstrated that lipopolysaccharide (LPS) caused the transepithelial resistance to drop to 387.5 ± 30.41 Ω·cm 2 , while IAA was able to increase it to 542 ± 31.11 Ω·cm 2 . At the same time, it reduced the paracellular permeability and restored the FITC‐Dextran 4 (FD‐4) permeability to 108.01%. This phenomenon was accompanied by an upregulation in the expression of tight junction (TJ) proteins. Concurrently, after IAA intervention, aryl hydrocarbon receptor (AHR) pathway was activated, while nuclear factor kappa‐B (NF‐κB) pathway was significantly inhibited. Furthermore, IAA exerted an inhibitory effect on the LPS‐triggered upregulation of inflammatory factors (TNF‐α, IL‐6, IL‐8) in RAW264.7 cells. These findings provide novel insights into the enhancement of intestinal barrier function and the in vitro anti‐inflammatory properties of gut microbiota‐derived metabolites.
Sun et al. (Thu,) studied this question.