An excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo.
FIG:The characteristics of the differentially expressed genes (DEGs), major enriched KEGG pathways involved in immune response for DEGs, and Protein–protein interaction network. DEGs between the groups were identified with edgeR method, using RStudio, Version 4.0.2 (RStudio team (2020). RStudio: Integrated Development for R. RStudio, PBC, Boston, MA URL). DEGs in H4 cells that were defined as those whose expression values with a set of |log2-Fold Change| ≥ 0.4 and FDR < 0.05.
The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.
Huang, W., Cho, K.Y., Meng, D. et al. The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis. Sci Rep 11, 8088 (2021). https://doi.org/10.1038/s41598-021-87353-1