Clostridium butyricum Protects Against Pancreatic and Intestinal Injury After Severe Acute Pancreatitis via Downregulation of MMP9.
Clostridium butyricum Protects Against Pancreatic and Intestinal Injury After Severe Acute Pancreatitis via Downregulation of MMP9.
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丁酸梭菌通过下调 MMP9 来预防严重急性胰腺炎后的胰腺和肠道损伤
DOI：
10.3389/fphar.2022.919010
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发表时间：
2022
影响因子：
5.6
通讯作者：
Wang, Qing
中科院分区：
文献类型：
--
作者：
Yan, Qingqing;Jia, Lin;Wen, Biyan;Wu, Yao;Zeng, Yanbo;Wang, Qing
关键词：
背景：有证据表明，肠道微生物群在严重急性胰腺炎（SAP）的发展中起着重要作用。此外，基质金属蛋白酶-9 （matrix metalloproteinase-9, MMP9）在SAP的肠道损伤中起重要作用。因此，我们旨在确定肠道微生物群是否可以通过调节MMP9来调节SAP过程中的肠道损伤。方法：采用16S rRNA基因测序方法对72例SAP患者和32例健康对照者的粪便样本进行分析。此外，为了研究肠道微生物群与MMP9在SAP期间肠道损伤中的关系，我们在体外建立了MMP9稳定敲除Caco2和HT29细胞，并在体内建立了MMP9敲除（MMP9−/−）的SAP小鼠模型。结果：我们发现SAP组丁酸梭菌（C. butyricum）的丰度显著降低。此外，过表达MMP9显著下调Caco2和HT29细胞中紧密连接蛋白的表达，上调p-p38和p- erk的表达（p < 0.05）。而在MMP9过表达的Caco2和HT29细胞中，丁酸c或丁酸处理显著上调了紧密连接蛋白的表达，下调了MMP9、p-p38和p- erk的表达（p < 0.05）。重要的是，与MMP9敲低组相比，丁酸c或丁酸盐不影响MMP9敲低组细胞中紧密连接蛋白、MMP9、p-p38和p-ERK蛋白的表达。与SAP组相比，丁酸梭菌或丁酸梭菌均不能减轻MMP9−/−小鼠在SAP过程中的胰腺和肠道损伤。结论：综上所述，丁酸梭菌通过下调体内和体外MMP9的表达，对胰脏和肠道损伤具有保护作用。
Background: Evidence have shown that gut microbiota plays an important role in the development of severe acute pancreatitis (SAP). In addition, matrix metalloproteinase-9 (MMP9) plays an important role in intestinal injury in SAP. Thus, we aimed to determine whether gut microbiota could regulate the intestinal injury during SAP via modulating MMP9. Methods: In this study, the fecal samples of patients with SAP (n = 72) and healthy controls (n = 32) were analyzed by 16S rRNA gene sequencing. In addition, to investigate the association between gut microbiota and MMP9 in intestinal injury during SAP, we established MMP9 stable knockdown Caco2 and HT29 cells in vitro and generated a MMP9 knockout (MMP9−/−) mouse model of SAP in vivo. Results: We found that the abundance of Clostridium butyricum (C. butyricum) was significantly decreased in the SAP group. In addition, overexpression of MMP9 notably downregulated the expressions of tight junction proteins and upregulated the expressions of p-p38 and p-ERK in Caco2 and HT29 cells (p < 0.05). However, C. butyricum or butyrate treatment remarkably upregulated the expressions of tight junction proteins and downregulated the expressions of MMP9, p-p38 and p-ERK in MMP9-overexpressed Caco2 and HT29 cells (p < 0.05). Importantly, C. butyricum or butyrate could not affect the expressions of tight junction proteins, and MMP9, p-p38 and p-ERK proteins in MMP9-knockdown cells compared with MMP9-knockdown group. Consistently, C. butyricum or butyrate could not attenuate pancreatic and intestinal injury during SAP in MMP9−/− mice compared with the SAP group. Conclusion: Collectively, C. butyricum could protect against pancreatic and intestinal injury after SAP via downregulation of MMP9 in vitro and in vivo.
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