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Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine
Pediatric Research ( IF 3.1 ) Pub Date : 2020-01-16 , DOI: 10.1038/s41390-019-0740-x
Di Meng 1 , Eduardo Sommella 2 , Emanuela Salviati 2, 3 , Pietro Campiglia 2, 4 , Kriston Ganguli 1 , Karim Djebali 1 , Weishu Zhu 1 , W Allan Walker 1, 4
Affiliation  

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. 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. 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-1β stimulus. It interacts with the transcription factor aryl hydrocarbon receptor (AHR) and prevents transcription of the inflammatory cytokine IL-8. 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.

中文翻译:

Indole-3-乳酸是一种色氨酸的代谢物,由婴儿长双歧杆菌分泌,在未成熟的肠道中具有抗炎作用

坏死性小肠结肠炎 (NEC) 是一种肠道坏死性炎症,是极早产儿的主要健康问题。虽然预防很困难,但摄入母体分泌的母乳与益生菌相结合可提供最佳保护。在这项研究中,我们建立了母乳/益生菌保护机制。长双歧杆菌亚种的超高效液相色谱-串联质谱。infantis (B. infantis) 分泌物用于鉴定抗炎分子。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的人类肠样体中测试吲哚-3-乳酸 (ILA) 的抗炎作用并建立发育功能。还在未成熟和成熟的肠细胞中检查了 ILA。我们已将 ILA(母乳色氨酸的代谢物)鉴定为抗炎分子。该分子在未成熟但不成熟的肠肠细胞中具有发育功能;ILA 在 IL-1β 刺激后降低白细胞介素 8 (IL-8) 反应。它与转录因子芳烃受体 (AHR) 相互作用并阻止炎症细胞因子 IL-8 的转录。这种由婴儿双歧杆菌 (ATCC No. 15697) 产生的分子以互补的方式与摄入的母乳相互作用,如果进行安全性和临床研究,可用于治疗所有 NEC 高危早产儿。该分子在未成熟但不成熟的肠肠细胞中具有发育功能;ILA 在 IL-1β 刺激后降低白细胞介素 8 (IL-8) 反应。它与转录因子芳烃受体 (AHR) 相互作用并阻止炎症细胞因子 IL-8 的转录。这种由婴儿双歧杆菌 (ATCC No. 15697) 产生的分子以互补的方式与摄入的母乳相互作用,如果进行安全性和临床研究,可用于治疗所有 NEC 高危早产儿。该分子在未成熟但不成熟的肠肠细胞中具有发育功能;ILA 在 IL-1β 刺激后降低白细胞介素 8 (IL-8) 反应。它与转录因子芳烃受体 (AHR) 相互作用并阻止炎症细胞因子 IL-8 的转录。这种由婴儿双歧杆菌 (ATCC No. 15697) 产生的分子以互补的方式与摄入的母乳相互作用,如果进行安全性和临床研究,可用于治疗所有 NEC 高危早产儿。
更新日期:2020-01-16
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