结合肠道微生物的非靶向代谢组学和伪靶向脂质组学揭示了Causonis japonica (Thunb.) Raf.对溃疡性结肠炎小鼠的保护作用。

IF 4.6 2区 医学 Q2 IMMUNOLOGY Frontiers in Cellular and Infection Microbiology Pub Date : 2024-10-15 eCollection Date: 2024-01-01 DOI:10.3389/fcimb.2024.1397735
Hua Huang, Jie Jiang, Yihua Fan, Xufeng Ding, Fang Li, Chuanxin Liu, Lijiang Ji
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引用次数: 0

摘要

溃疡性结肠炎(UC)是一种炎症性肠病,其特征是肠粘膜反复出现炎性组织损伤并形成肠上皮溃疡。它是世界上最难治愈的疾病之一。迄今为止,其发病机制尚不清楚。中药五莲糖具有抗炎作用,历史悠久,但其对 UC 的作用尚未得到证实。因此,我们建立了右旋糖酐硫酸钠(DSS)诱导的 UC 小鼠模型,并评估了 WLM 提取物的治疗效果。结果表明,WLM 可抑制 DSS 诱导的体内结肠炎炎症反应,减少 DSS 诱导的临床表现,逆转结肠长度缩短,减少组织损伤。酶联免疫吸附试验结果表明,WLM 可逆转 DSS 诱导的炎症因子水平。为了探索WLM治疗DSS诱导的UC的机制,研究人员利用1H NMR和UHPLC-Q/Orbitrap MS进行了非靶向代谢组学分析,结果显示结肠组织中的21种差异代谢物与UC密切相关。同时,利用基于 UHPLC-Q/Trap MS 的伪靶向脂质组学分析脂质代谢紊乱,筛选出 60 种差异脂质化合物。这些差异化合物主要涉及甘油磷脂、花生四烯酸、甘油酯、柠檬酸、酪氨酸和醚类脂质代谢。对肠道微生物的分析表明,WLM 可通过减少螺旋杆菌和链球菌的数量,增加乳酸杆菌和阿克曼菌的数量来改善 UC 小鼠的症状。此外,实时 qPCR 结果表明,WLM 提取物可降低炎症因子的 mRNA 水平,可能与通过破坏体内代谢途径,特别是通过调节能量和脂质代谢以及减少炎症反应来保护肠粘膜屏障的完整性有关。这为研究 WLM 以阐明 UC 的治疗机制提供了有益的参考。
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Non-targeted metabolomics and pseudo-targeted lipidomics combined with gut microbes reveal the protective effects of Causonis japonica (Thunb.) Raf. in ulcerative colitis mice.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammatory tissue damage to the intestinal mucosa and forming intestinal epithelial ulcers. It is one of the most intractable diseases in the world. To date, the mechanism is unclear. Causonis japonica (Thunb.) Raf. (Wu Lianmei in Chinese; WLM), a traditional Chinese medicine, which has a long history as an anti-inflammatory, but its effect on UC was unconfirmed yet. Therefore, we established a dextran sodium sulfate (DSS)-induced UC mice model and evaluated the therapeutic effect of WLM extract. The results indicated that WLM inhibits DSS-induced inflammatory response in colitis in vivo, decrease DSS-induced clinical manifestations, reverses colon length shortening, and reduces tissue damage. The results of ELISA kits suggested that WLM could reverse the levels of DSS-induced inflammatory factors. To explore the mechanism of WLM in treating DSS-induced UC, 1H NMR and UHPLC-Q/Orbitrap MS were used to perform non-targeted metabolomics analysis; 21 differential metabolites in colon tissues were closely related to UC. Meanwhile, the pseudo-targeted lipidomics based on UHPLC-Q/Trap MS was used to analyze lipid metabolism disorders, and 60 differential lipid compounds were screened. These differential compounds were mainly involved in glycerophospholipid, arachidonic acid, glycerolipid, citric acid, tyrosine, and ether lipid metabolisms. The analysis of gut microbial showed that WLM may improve the symptoms of UC mice by reducing the abundance of Helicobacter and Streptococcus and increasing the abundance of Limosilactobacillus and Akkermansia. Moreover, the real-time qPCR results showed that WLM extract could decrease the mRNA levels of inflammatory factors and may be associated with protecting the integrity of intestinal mucosal barrier by destroying in vivo metabolic pathways, especially by regulating energy and lipid metabolisms and reducing inflammatory reactions. It provides a beneficial reference for studying WLM to elucidate the therapeutic mechanism of UC.

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来源期刊
CiteScore
7.90
自引率
7.00%
发文量
1817
审稿时长
14 weeks
期刊介绍: Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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