Institute of Agro-Product Processing, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China.
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Harvard Medical School, 16th Street Building (114-3503), Charlestown, MA, 02129, USA.
Sci Rep. 2021 Apr 13;11(1):8088. doi: 10.1038/s41598-021-87353-1.
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. 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.
过度的肠道炎症反应可能在极早产儿坏死性小肠结肠炎 (NEC) 的发病机制中起作用。母乳色氨酸的吲哚-3-乳酸 (ILA) 被鉴定为参与长双歧杆菌亚种婴儿益生菌调理培养基的抗炎代谢物。本研究旨在探索参与保护性 ILA 对抗炎症的分子内吞途径。使用 H4 细胞、Caco-2 细胞、C57BL/6 幼鼠和成年小鼠，在体外和体内比较未成熟和成熟肠细胞之间的抗炎机制。结果表明，ILA 对未成熟肠细胞具有多种保护作用，包括抗炎、抗病毒和发育调节潜能，具有区域依赖性和年龄依赖性。定量转录组分析揭示了一种新的机制模型，其中 STAT1 途径在 IL-1β 诱导的炎症中发挥重要作用，而 ILA 对 STAT1 途径具有调节作用。这些研究通过实时 RT-qPCR 和 STAT1 抑制剂实验得到了验证。ILA 在未成熟和成熟肠细胞之间的不同保护反应表明，ILA 的作用是发育调节的。这些发现可能有助于预防早产儿 NEC。
