Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota.
Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota.
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妊娠期肝内胆汁淤积通过调节肠道微生物群增加新生儿后代的炎症易感性
DOI：
10.3389/fimmu.2022.889646
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
妊娠期肝内胆汁淤积症（ICP）是一种妊娠期肝病，其特征是母体血清中胆汁酸水平升高。研究表明，胆汁淤积性妊娠可导致后代长期代谢紊乱。然而，ICP如何在早期阶段塑造后代的免疫力和炎症性疾病的易感性尚不清楚。在这项研究中，我们探讨了母亲胆汁淤积对新生儿代谢和免疫功能的影响。我们比较了71名ICP母亲的新生儿和63名健康母亲的新生儿，发现ICP后代的黄疸和感染发生率明显较高。母亲血清总胆汁酸水平与足月ICP后代的血细胞计数相关。在动物实验中，在ICP后代中发现了肝脏和回肠法尼醇X受体（FXR）的代偿性激活以及第一周肠道微生物群的改变。我们还研究了脂多糖（LPS）诱导的新生大鼠炎症反应，发现ICP后代更容易受到炎症的影响。为了了解先天性异常FXR激活和组织免疫失调之间的相关性，我们评估了FXR激动剂GW 4064和FXR拮抗剂E/Z-GS在LPS暴露后ICP后代中的作用。用E/Z-GS处理后几种促炎细胞因子的表达显著降低，但用GW 4064处理后增加。用益生菌鼠李糖乳杆菌LRX 01抑制回肠中FXR表达，降低ICP后代对LPS暴露的易感性。目前的研究表明，胆汁淤积性妊娠可能通过改变早期胆汁酸代谢和肠道微生物群来增加后代对炎症的易感性。我们认为，补充鼠李糖乳杆菌LRX 01，抑制FXR在回肠的表达，可能会提高ICP后代的肠道免疫力。
Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that is characterized by increased bile acid levels in maternal serum. Studies have shown that cholestatic pregnancy can result in long-term metabolic disturbances in the offspring. However, how ICP shapes the offspring’s immunity and predisposition to inflammatory disorders at an early stage is unknown. In this study, we investigated the effect of maternal cholestasis on neonatal offspring metabolism and immune function. We compared 71 neonates with ICP mothers and 63 neonates with healthy mothers and found that the incidence of jaundice and infection was significantly higher in ICP offspring. Maternal serum total bile acid level was associated with blood cell counts in full-term ICP offspring. In animal experiments, a compensatory activation of hepatic and ileal farnesoid X receptor (FXR) and altered gut microbiota in the first week were found in ICP offspring. We also investigated lipopolysaccharide (LPS)-induced inflammatory responses in neonatal rats and found that ICP offspring were more susceptible to inflammation. To understand the correlation between congenital abnormal FXR activation and tissue immunity dysregulation, we assessed the effects of the FXR agonist GW4064 and FXR antagonist E/Z-GS in ICP offspring after LPS exposure. The expression of several pro-inflammatory cytokines significantly decreased after treatment with E/Z-GS but increased after treatment with GW4064. Treatment with the probiotic Lactobacillus rhamnosus LRX01 that inhibits FXR expression in the ileum reduced susceptibility to LPS exposure in ICP offspring. The current study indicated that cholestatic pregnancy may increase the susceptibility of the offspring to inflammation by altering bile acid metabolism and gut microbiota at an early stage. We suggest that supplementation with Lactobacillus rhamnosus LRX01, which inhibits FXR expression in the ileum, may improve intestinal immunity in ICP offspring.
影响因子：
2.6
作者：
Teng J;Elwin A;Omarsdottir S;Aquilano G;Vanpee M;Nemeth A;Rahbar A;Bohlin K;Fischler B;Söderberg-Nauclér C
通讯作者：
Söderberg-Nauclér C