Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis.
Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis.
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肠道微生物群衍生的二氨基庚二酸促进 NOD1/RIP2 信号通路并在重症急性胰腺炎的进展中发挥关键作用
DOI：
10.3389/fcimb.2022.838340
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
肠屏障功能受损和肠道菌群失调被认为与急性胰腺炎（AP）的恶化有关。二氨基庚二酸（diaminopimelic acid，DAP）是NOD 1的特异性配体，作为细菌细胞壁肽聚糖组分，调节NOD 1/RIP 2/NF-kB信号通路。在这里，我们研究了DAP在AP发生期间肠道微生物群和胰腺之间的串扰中的作用。重症急性胰腺炎（SAP）模型组NOD 1/RIP 2/NF-kB表达上调，血清DAP水平升高。SAP患者中DAP的积累证实了其作为疾病严重程度指标的能力。随后，SAP大鼠口服中药清胰颗粒（QYKL）以及新霉素，这可以广泛地消除含DAP的细菌。清胰颗粒和新霉素干预均能减轻SAP大鼠肠、胰腺损伤及全身炎症反应。通过16 S rDNA测序，我们发现QYKL可以修复SAP大鼠的肠道微生物群结构，并选择性地抑制肠道细菌如螺杆菌和乳酸杆菌的过度生长，而不影响一些保护性菌株，包括Romboutsia和Allobaculum。有趣的是，我们证明了血清DAP的降低伴随着两个干预组的肠和胰腺中NOD 1/RIP 2/NF-kB信号通路的抑制。综上所述，这些结果表明，肠道微生物-DAP-NOD 1/RIP 2信号通路可能在AP的进展中起关键作用，并且可以通过干预该信号通路来缓解SAP。我们的工作提供了新的潜在的SAP预警指标和干预目标。
Impaired intestinal barrier function and gut microbiota dysbiosis are believed to be related to exacerbation of acute pancreatitis (AP). As a bacterial cell wall peptidoglycan component, diaminopimelic acid (DAP) is a specific ligand of NOD1 that regulates the NOD1/RIP2/NF-kB signaling pathway. Here, we investigated the role of DAP in the crosstalk between the gut microbiota and pancreas during the occurrence of AP. Upregulation of NOD1/RIP2/NF-kB and elevated serum DAP levels were found in severe AP (SAP) model rats. The accumulation of DAP in SAP patients corroborated its ability to serve as an indicator of disease severity. Subsequently, SAP rats were treated with oral administration of the traditional Chinese medicine Qingyi Keli (QYKL) as well as neomycin, which can widely eliminate DAP-containing bacteria. Both QYKL and neomycin intervention ameliorated intestinal and pancreatic damage and systemic inflammation in SAP rats. Through 16S rDNA sequencing, we found that QYKL could rehabilitate the gut microbiota structure and selectively inhibit the overgrowth of enteric bacteria, such as Helicobacter and Lactobacillus, in SAP rats without affecting some protective strains, including Romboutsia and Allobaculum. Interestingly, we demonstrated that the decrease in serum DAP was accompanied by suppression of the NOD1/RIP2/NF-kB signaling pathway in both the intestine and pancreas of the two intervention groups. Taken together, these results suggested that the gut microbiota-DAP-NOD1/RIP2 signaling pathway might play a critical role in the progression of AP and that SAP could be alleviated via intervention in the signaling pathway. Our work provides new potential early warning indicators of SAP and targets for intervention.
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影响因子：
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作者：
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发表时间：
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影响因子：
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