NEC-like intestinal injury is ameliorated by Lactobacillus rhamnosus GG in parallel with SIGIRR and A20 induction in neonatal mice.
NEC-like intestinal injury is ameliorated by Lactobacillus rhamnosus GG in parallel with SIGIRR and A20 induction in neonatal mice.
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DOI：
10.1038/s41390-020-0797-6
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发表时间：
2020-10
影响因子：
3.6
通讯作者：
Sampath V
中科院分区：
文献类型：
--
作者：
Cuna A;Yu W;Menden HL;Feng L;Srinivasan P;Chavez-Bueno S;Ahmed I;Umar S;Sampath V
Toll样受体（TLR）信号转导和肠道生态失调是坏死性小肠结肠炎（NEC）的关键因素。鼠李糖乳杆菌GG（LGG）可降低早产儿NEC，但其潜在的保护机制仍知之甚少。我们假设LGG促进微生态失调并上调TLR抑制剂以保护免受TLR介导的肠道损伤。测定LGG（低剂量和高剂量）对配方奶粉喂养（FF）和NEC新生小鼠肠道促炎TLR信号传导和损伤的影响。分析粪便16 S测序和抗TLR介质单免疫球蛋白白细胞介素-1相关受体（SIGIRR）和A20的表达。与对照组相比，FF诱导轻度肠损伤，白细胞介素-1 β（IL-1β）和KC（IL-8的小鼠同系物）表达增加。LGG以剂量依赖性方式降低IL-1β和KC，减弱TLR信号传导，增加SIGIRR和A20表达。低剂量和高剂量LGG对肠道微生物组有不同的影响，尽管两种剂量都提供了肠道保护。随后的LGG对NEC的实验显示，LGG预处理的促炎TLR信号传导和肠损伤也以剂量依赖性方式降低，SIGIRR和A20表达增加。LGG通过上调TLR抑制剂来保护肠道TLR介导的损伤，而肠道微生物组组成没有重大变化。
Exaggerated Toll-like receptor (TLR) signaling and intestinal dysbiosis are key contributors to necrotizing enterocolitis (NEC). Lactobacillus rhamnosus GG (LGG) decreases NEC in preterm infants, but underlying mechanisms of protection remain poorly understood. We hypothesized that LGG alleviates dysbiosis and upregulates TLR inhibitors to protect against TLR-mediated gut injury. Effects of LGG (low- and high-dose) on intestinal pro-inflammatory TLR signaling and injury in neonatal mice subjected to formula-feeding (FF) and NEC were determined. 16S sequencing of stool and expression of anti-TLR mediators Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) and A20 were analyzed. FF induced mild intestinal injury with increased expression of interleukin-1 beta (IL-1β) and KC (mouse homolog of IL-8) compared to controls. LGG decreased IL-1β and KC in association with attenuated TLR signaling and increased SIGIRR and A20 expression in a dose-dependent manner. Low- and high-dose LGG had varying effects on gut microbiome despite both doses providing gut protection. Subsequent experiments of LGG on NEC revealed that pro-inflammatory TLR signaling and intestinal injury were also decreased, and SIGIRR and A20 expression increased, in a dose-dependent manner with LGG pre-treatment. LGG protects against intestinal TLR-mediated injury by upregulating TLR inhibitors without major changes in gut microbiome composition.
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影响因子：
1.7
作者：
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通讯作者：
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影响因子：
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DOI：
10.1136/archdischild-2011-300435
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