微生物组功能紊乱已被证实加重急性胰腺炎（AP）；然而，这种功能紊乱与代谢物改变之间的关系尚不完全清楚。本研究探讨了在AP小鼠中微生物组和代谢物之间的相互作用。通过给予C57/BL小鼠七剂丝裂原负载脂多糖（LPS），建立了实验性AP模型。使用宏基因组学和非靶向代谢组学来鉴定AP进展过程中微生物组和代谢物的系统异常。 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，并且伴有蛋白变形菌门增加和放线菌门减少的“核心微生物”。《基因与基因组的京都百科全书》分析发现，多个信号网络中出现了明显不同的微生物群落。非靶向代谢组学鉴定了872种代谢物，其中脂质和类脂质分子受到最大影响。宏基因组学和非靶向代谢组学的整合分析表明，丙酸激酶（ackA）基因表达与多种肠道菌群（包括变形菌属、丁酸单胞菌属和乳酸杆菌）相关，并与代谢物daphnoretin强相关。功能基因 O-乙酰-L-丝氨酰硫氢酶（cysK）与变形菌属、Dinggalicoccus和乳酸杆菌相关，并与bufalin和phlorobenzophenone代谢物的合成相关。 本研究确定了AP期间肠道微生物组和代谢物水平之间的关系，特别是与乳酸杆菌、变形菌属和丁酸单胞菌相关的功能基因ackA和cysK。这些基因的表达与抗炎和抗肿瘤代谢物daphnoretin和bufalin的产生显著相关。 版权所有 © 2023 Zhou, Tao, Guo, Zhu, Wu, Xiang and Shang.

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.Copyright © 2023 Zhou, Tao, Guo, Zhu, Wu, Xiang and Shang.