Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.
Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.
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副芽胞杆菌产生醋酸酯，通过减少中性粒细胞浸润来减轻肝素酶加重的急性胰腺炎。
DOI：
10.1186/s40168-021-01065-2
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发表时间：
2021-05-20
期刊：
影响因子：
15.5
通讯作者：
Yang S
中科院分区：
文献类型：
--
作者：
Lei Y;Tang L;Liu S;Hu S;Wu L;Liu Y;Yang M;Huang S;Tang X;Tang T;Zhao X;Vlodavsky I;Zeng S;Tang B;Yang S
内切糖苷酶乙酰肝素酶可降解硫酸乙酰肝素蛋白聚糖，在多种炎症性疾病中发挥促炎介质作用。然而，乙酰肝素酶在急性胰腺炎中的功能和潜在机制仍知之甚少。在这里，我们研究了乙酰肝素酶和肠道微生物群在急性胰腺炎发生过程中的相互作用。通过给予雨蛙素，在野生型和乙酰肝素酶转基因小鼠中诱导急性胰腺炎。通过 16S 核糖体 RNA 测序分析肠道微生物群的差异。使用抗生素鸡尾酒实验、粪便微生物群移植和共养实验来评估肠道微生物群的作用。与野生型小鼠相比，乙酰肝素酶转基因小鼠的急性胰腺炎病情加重。此外，乙酰肝素酶转基因小鼠和野生型小鼠的肠道微生物群也不同。乙酰肝素酶以肠道微生物群依赖性方式加剧急性胰腺炎。特别是，共生副拟杆菌对区分野生型和乙酰肝素酶转基因小鼠之间的差异贡献最大。给予副拟杆菌可以减轻野生型和乙酰肝素酶转基因小鼠的急性胰腺炎。此外，副拟杆菌产生乙酸盐，通过减少中性粒细胞浸润来缓解乙酰肝素酶恶化的急性胰腺炎。肠-胰腺轴在急性胰腺炎的发生过程中发挥着重要作用，副杆菌产生的乙酸可能有益于急性胰腺炎的治疗。视频摘要 在线版本包含可在 10.1186/s40168-021-01065-2 获取的补充材料。
The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function and underlying mechanism of heparanase in acute pancreatitis remain poorly understood. Here, we investigated the interplay between heparanase and the gut microbiota in the development of acute pancreatitis. Acute pancreatitis was induced in wild-type and heparanase-transgenic mice by administration of caerulein. The differences in gut microbiota were analyzed by 16S ribosomal RNA sequencing. Antibiotic cocktail experiment, fecal microbiota transplantation, and cohousing experiments were used to assess the role of gut microbiota. As compared with wild-type mice, acute pancreatitis was exacerbated in heparanase-transgenic mice. Moreover, the gut microbiota differed between heparanase-transgenic and wild-type mice. Heparanase exacerbated acute pancreatitis in a gut microbiota-dependent manner. Specially, the commensal Parabacteroides contributed most to distinguish the differences between wild-type and heparanase-transgenic mice. Administration of Parabacteroides alleviated acute pancreatitis in wild-type and heparanase-transgenic mice. In addition, Parabacteroides produced acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration. The gut–pancreas axis played an important role in the development of acute pancreatitis and the acetate produced by Parabacteroides may be beneficial for acute pancreatitis treatment. Video abstract The online version contains supplementary material available at 10.1186/s40168-021-01065-2.
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影响因子：
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作者：
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通讯作者：
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