The crosstalk between microbiota and metabolites in AP mice: an analysis based on metagenomics and untargeted metabolomics.

The crosstalk between microbiota and metabolites in AP mice: an analysis based on metagenomics and untargeted metabolomics.
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AP小鼠中微生物群和代谢物之间的串扰:基于宏基因组学和非靶向代谢组学的分析

DOI:
10.3389/fcimb.2023.1134321
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发表时间:
2023
影响因子:
5.7
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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已知微生物组功能障碍会加重急性胰腺炎(AP);然而,这种功能障碍与代谢物改变之间的关系尚未完全了解。这项研究探讨了AP小鼠中微生物组和代谢物之间的串扰。用7个剂量的雨蛙肽和1个剂量的脂多糖(LPS)注射C57/BL小鼠建立实验性AP模型。宏基因组学和非靶向代谢组学分别用于确定AP进展期间微生物组和代谢物的系统性紊乱。AP小鼠的肠道微生物组主要包括厚壁菌门、拟杆菌门、放线菌门和变形菌门,以及以变形菌门增加和放线菌门减少为特征的“核心微生物群”。京都基因和基因组百科全书(KEGG)分析发现,几种信号网络中涉及显著不同的微生物。非靶向代谢组学确定了872种代谢物,其中脂质和脂质样分子受到的影响最大。宏基因组学和代谢组学的综合分析表明,乙酸激酶(ackA)基因表达与各种肠道微生物群,包括Alistipes,Butyricimonas和Lactobacillus,并与代谢产物daphnoretin密切相关。功能基因,O-乙酰-L-丝氨酸硫化氢解酶(cysK),与Alistipes,Jeotgalicoccus,和乳酸杆菌,并链接到蟾蜍灵和间苯二苯甲酮代谢产物的生产。这项研究确定了AP期间肠道微生物组和代谢物水平之间的关系,特别是乳酸杆菌,Alistipes和Butyricimonas相关功能基因ackA和cysK。这些基因的表达显着相关的抗炎和抗肿瘤代谢产物daphnoretin和蟾蜍灵的生产。
Microbiome dysfunction is known to aggravate acute pancreatitis (AP); however, the relationship between this dysfunction and metabolite alterations is not fully understood. This study explored the crosstalk between the microbiome and metabolites in AP mice. Experimental AP models were established by injecting C57/BL mice with seven doses of cerulein and one dose of lipopolysaccharide (LPS). Metagenomics and untargeted metabolomics were used to identify systemic disturbances in the microbiome and metabolites, respectively, during the progression of AP. The gut microbiome of AP mice primarily included Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, and “core microbiota” characterized by an increase in Proteobacteria and a decrease in Actinobacteria. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that significantly different microbes were involved in several signaling networks. Untargeted metabolomics identified 872 metabolites, of which lipids and lipid-like molecules were the most impacted. An integrated analysis of metagenomics and metabolomics indicated that acetate kinase (ackA) gene expression was associated with various gut microbiota, including Alistipes, Butyricimonas, and Lactobacillus, and was strongly correlated with the metabolite daphnoretin. The functional gene, O-acetyl-L-serine sulfhydrylase (cysK), was associated with Alistipes, Jeotgalicoccus, and Lactobacillus, and linked to bufalin and phlorobenzophenone metabolite production. This study identified the relationship between the gut microbiome and metabolite levels during AP, especially the Lactobacillus-, Alistipes-, and Butyricimonas-associated functional genes, ackA and cysK. Expression of these genes was significantly correlated to the production of the anti-inflammatory and antitumor metabolites daphnoretin and bufalin.
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