Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine
Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine
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DOI：
10.1038/s41390-019-0740-x
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发表时间：
2020-01-16
影响因子：
3.6
通讯作者：
Walker, W. Allan
中科院分区：
文献类型：
--
作者：
Meng, Di;Sommella, Eduardo;Walker, W. Allan
背景坏死性小肠结肠炎（NEC）是一种小肠坏死性炎症，是早产儿的主要健康问题。虽然预防是困难的，但结合摄入母体分泌的母乳和益生菌提供了最好的保护。在本研究中，我们建立了母乳/益生菌保护机制。方法超高效液相色谱-串联质谱法测定长双歧杆菌亚群。利用婴儿（B. infantis）分泌物鉴定抗炎分子。然后在已建立的人类未成熟小肠细胞系、坏死性结肠炎肠细胞和其他未成熟人类肠样细胞中测试吲哚-3-乳酸（ILA）的抗炎作用和建立发育功能。在未成熟和成熟肠细胞中也检测了ILA。结果确定母乳色氨酸的代谢物ILA为抗炎分子。该分子在未成熟而非成熟的肠细胞中具有发育功能；ILA降低IL-1 β刺激后的白细胞介素-8 （IL-8）反应。它与转录因子芳烃受体（AHR）相互作用，阻止炎症细胞因子IL-8的转录。结论：这种由B. infant （ATCC No. 15697）产生的分子与摄入的母乳功能以互补的方式相互作用，如果进行安全性和临床研究，可能用于治疗所有高危早产儿NEC。
Background Necrotizing enterocolitis (NEC), a necrotic inflammation of the intestine, represents a major health problem in the very premature infant. Although prevention is difficult, the combination of ingestion of maternal-expressed breastmilk in conjunction with a probiotic provides the best protection. In this study, we establish a mechanism for breastmilk/probiotic protection. Methods Ultra-high-performance liquid chromatography-tandem mass spectrometry of Bifidobacterium longum subsp. infantis (B. infantis) secretions was used to identify an anti-inflammatory molecule. Indole-3-lactic acid (ILA) was then tested in an established human immature small intestinal cell line, necrotizing colitis enterocytes, and other immature human enteroids for anti-inflammatory effects and to establish developmental function. ILA was also examined in immature and mature enterocytes. Results We have identified ILA, a metabolite of breastmilk tryptophan, as the anti-inflammatory molecule. This molecule is developmentally functional in immature but not mature intestinal enterocytes; ILA reduces the interleukin-8 (IL-8) response after IL-1 beta stimulus. It interacts with the transcription factor aryl hydrocarbon receptor (AHR) and prevents transcription of the inflammatory cytokine IL-8. Conclusions This molecule produced by B. infantis (ATCC No. 15697) interaction with ingested breastmilk functions in a complementary manner and could become useful in the treatment of all at-risk premature infants for NEC if safety and clinical studies are performed.