Gut microbiota-derived metabolites in inflammatory diseases based on targeted metabolomics.

Gut microbiota-derived metabolites in inflammatory diseases based on targeted metabolomics.
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基于靶向代谢组学的炎症性疾病中肠道微生物衍生代谢物。

DOI:
10.3389/fphar.2022.919181
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发表时间:
2022
影响因子:
5.6
通讯作者:
Wang, Yan
Wang, Yan
中科院分区:
医学2区
文献类型:
--
作者:
Xu, Hui;Pan, Li-Bin;Yu, Hang;Han, Pei;Fu, Jie;Zhang, Zheng-Wei;Hu, Jia-Chun;Yang, Xin-Yu;Keranmu, Adili;Zhang, Hao-Jian;Bu, Meng-Meng;Jiang, Jian-Dong;Wang, Yan

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肠道菌群在炎症性疾病中起着重要作用。色氨酸(Trp)、组氨酸(His)和苯丙氨酸(Phe)三种代谢途径中的代谢物可影响各种炎症,如肥胖、糖尿病、关节炎、结肠炎、动脉粥样硬化和神经炎症。建立了LC-MS /MS方法,测定了3-吲哚-乙酸(Iaa)、3-吲哚-乳酸(Ila)、3-吲哚-丙酸(Ipa)、3-吲哚甲醛(Iald)、犬尿氨酸(Kn)、犬尿酸(Kyna)、3-羟基苯甲酸(3-Haa)、His、3-甲基组氨酸(3-Mhis)、组胺(Hist)、咪唑丙酸(Imp)、4-咪唑乙酸(Imaa)、尿酸(Ua)、苯乙胺(Pea)、马尿酸(Ha)等17种代谢途径中的代谢物。方法灵敏度高,选择性好,线性度、准确度、精密度、稳定性好;和回收率;均满足生物样品分析要求。通过建立Sprague-Dawley大鼠类风湿关节炎(RA)模型,并对其粪便进行16S rRNA测序,发现其肠道细菌存在生态失调,包括门水平、属水平和α生物多样性的变化。模型组小鼠微生物代谢产物Iaa、Ipa含量显著降低,Iald、Kn、Kyna、Ha、Imp含量显著升高。通过与肠道细菌体外培养筛选常用治疗药物雷公藤多苷、牡丹总苷及其主要有效成分,发现雷公藤多苷及其有效成分可导致Trp和Phe通路代谢产物发生变化。牡丹总苷和活性成分可导致肠道微生物群Phe途径代谢产物的变化。
The gut microbiota plays an important role in inflammatory diseases. Metabolites in the three metabolic pathways of tryptophan (Trp), histidine (His), and phenylalanine (Phe) can affect various inflammatory conditions, such as obesity, diabetes, arthritis, colitis, atherosclerosis, and neuroinflammation. We established an LC–MS/MS method to measure 17 metabolites—Trp, 3-indole-acetic acid (Iaa), 3-indole-lactate (Ila), 3-indole-propionic acid (Ipa), 3-indole formaldehyde (Iald), kynurenine (Kn), kynurenic acid (Kyna), 3-Hydroxyanthranilic acid (3-Haa), His, 3-methylhistidine (3-Mhis), histamine (Hist), imidazole propionic acid (Imp), 4-imidazoacetic acid (Imaa), urocanic acid (Ua), Phe, phenylethylamine (Pea), and hippuric acid (Ha)—in the three metabolic pathways. The method exhibited high sensitivity and good selectivity, linearity, accuracy, precision, stability; and recovery rate; all met the requirements of biological sample analysis. By establishing a rheumatoid arthritis (RA) model of Sprague–Dawley rats and performing 16S rRNA sequencing on their feces, it was found that there was dysbiosis, including changes in phylum level, genus level, and α biodiversity of gut bacteria. The contents of the microbiota metabolites Iaa and Ipa in the model group were significantly decreased, and those of Iald, Kn, Kyna, Ha, and Imp were significantly increased. The common therapeutic drugs Tripterygium glycosides, total glucosides of peony, and their main active ingredients were screened by in vitro incubation with gut bacteria: it was found that Tripterygium glycosides and their active ingredients could lead to a variation in metabolites in the Trp and Phe pathways. Total glucosides and active components of peony could lead to a variation in metabolites in the Phe pathway of the gut microbiota.
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