Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway.
Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway.
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益生菌混合物通过调节 PXR-JNK 通路增强屏障功能以改善坏死性小肠结肠炎
DOI：
10.1186/s13578-021-00530-7
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发表时间：
2021-01-19
影响因子：
7.5
通讯作者：
Lv Z
中科院分区：
文献类型：
--
作者：
Zhao X;Zhou J;Liang W;Sheng Q;Lu L;Chen T;Chen J;Tan K;Lv Z
研究背景肠道菌群失调被认为是诱发新生儿坏死性小肠结肠炎（NEC）的因素之一。益生菌已在大量动物实验和临床试验中用于治疗 NEC，并且利用益生菌预防或缓解 NEC 的一些显着益处已得到证实。然而，益生菌治疗NEC的作用机制尚未阐明。结果NEC的发病机制中观察到以紧密连接成分表达减少为特征的肠道屏障受损。益生菌混合物通过增强屏障功能来减轻肠道损伤。同时，益生菌重塑了 NEC 小鼠肠道微生物群的组成。此外，用益生菌混合物处理后观察到孕烷 X 受体 (PXR) 表达增加，Caco-2 细胞中 PXR 过度表达可保护屏障免受脂多糖 (LPS) 损伤。进一步的研究表明，PXR可以抑制c-Jun氨基末端激酶（JNK）的磷酸化，并可以增加紧密连接成分的表达。结论我们的研究证实，益生菌可以通过增强粘膜屏障的功能来改善肠道病变。具体来说，益生菌可能以 PXR 为靶点，随后可能通过抑制 JNK 的磷酸化来增强紧密连接成分的表达，并增强屏障的功能。
BackgroundIntestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated.ResultsImpairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components.ConclusionsOur study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhance the function of the barrier.
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影响因子：
6.2
作者：
Cho, Steven X.;Berger, Philip J.;Nold-Petry, Claudia A.;Nold, Marcel F.
通讯作者：
Nold, Marcel F.
影响因子：
3.6
作者：
Jilling, T;Lu, J;Caplan, MS
通讯作者：
Caplan, MS
人坏死性小肠结肠炎中的肠屏障功能障碍。
影响因子：
2.4
作者：
Moore SA;Nighot P;Reyes C;Rawat M;McKee J;Lemon D;Hanson J;Ma TY
通讯作者：
Ma TY
影响因子：
64.8
作者：
De Smaele, E;Zazzeroni, F;Franzoso, G
通讯作者：
Franzoso, G
影响因子：
3.6
作者：
Maheshwari, Akhil;Schelonka, Robert L.;Dimmitt, Reed A.;Carlo, Waldemar A.;Munoz-Hernandez, Breda;Das, Abhik;McDonald, Scott A.;Thorsen, Poul;Skogstrand, Kristin;Hougaard, David M.;Higgins, Rosemary D.
通讯作者：
Higgins, Rosemary D.