Gut microbiome-derived indole-3-carboxaldehyde promotes intestinal development via AHR-NRF2 signaling in the early-life of chicks

BACKGROUND: The development of the small intestine is crucial during early life, with the gut microbiota and microbe-derived metabolites playing key roles in regulating intestinal epithelial barrier function and overall development. However, the underlying mechanism remains unclear. Here, chicks were used to investigate the influences of early-life crosstalk among bacteria, metabolites, and the host on small intestinal development. RESULTS: We investigated bacterial succession in the small intestine of broiler chicks at four time points during early development. After 3 days post-hatch, Bacillota became the dominant phylum. At the genus level, Lactobacillus and Ligilactobacillus emerged as the two dominant genera, and their abundance was significantly positively correlated with small intestine weight. Metabolome analysis revealed that indole-3-carboxaldehyde (IAld) is derived from both L. gallinarum C2-16-2 (LG) and L. salivarius D7-21 (LS). Moreover, we found that IAld can be converted into bioactive indole-3-carboxylic acid (ICA) in animals, which exhibited greater biological activity than IAld in vitro. Further chick feeding trials revealed that both bacteria (LG and LS) and metabolites (IAld and ICA) promoted epithelial barrier function and enhanced antioxidant capacity during early life in chicks. Moreover, both IAld and ICA promoted tight junction protein expression and enhanced antioxidant capacity by activating AHR-NRF2 signaling. CONCLUSIONS: These findings suggest that specific bacterial strains (L. gallinarum C2-16-2 and L. salivarius D7-21) and metabolites (IAld and ICA) serve as effective promoters of intestinal epithelial barrier function and antioxidant capacity during early intestinal development in chicks Video Abstract.