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2023 1

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2018 1

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代谢组 1

代谢组学 1

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昼夜节律 1

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肠道屏障功能紊乱 1

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花粉过敏 1

过敏性疾病 1

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Discovery of the mechanisms of acupuncture in the treatment of migraine based on functional magnetic resonance imaging and omics

《医学前沿（英文）》页码 993-1005 doi: 10.1007/s11684-023-0989-7

摘要： Migraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients’ metabolites/proteins may precede that of the brain.

关键词： acupuncture migraine fMRI metabolome proteome

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characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome

《医学前沿（英文）》 doi: 10.1007/s11684-023-1029-3

摘要： Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

关键词： tumor prognosis molecular Microbiome subsets determine center analysis microbiome transcriptome data

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Calorie restriction and its impact on gut microbial composition and global metabolism

Xiaojiao Zheng, Shouli Wang, Wei Jia

《医学前沿（英文）》 2018年第12卷第6期页码 634-644 doi: 10.1007/s11684-018-0670-8

摘要：

Calorie restriction (CR) is a dietary regimen that reduces calorie intake without incurring malnutrition or a reduction in essential nutrients. It has long been recognized as a natural strategy for promoting health, extending longevity, and prevents the development of metabolic and age-related diseases. In the present review, we focus on the general effect of CR on gut microbiota composition and global metabolism. We also propose mechanisms for its beneficial effect. Results showed that probiotic and butyrate-producing microbes increased their relative abundance, whereas proinflammatory strains exhibited suppressed relative abundance following CR. Analyses of the gut microbial and host metabolisms revealed that most host microbial co-metabolites were changed due to CR. Examples of dramatic CR-induced changes in host metabolism included a decrease in the rate of lipid biosynthesis and an increase in the rates of fatty acid catabolism, β-oxidation, glycogenolysis, and gluconeogenesis. The observed phenotypes and the further verification of the direct link between gut microbiota and metabolome may benefit patients that are at risk for developing metabolic disease. Thus, improved gut microbiota composition and metabolome are potential biomarkers for determining the effectiveness of dietary interventions for age-related and metabolic diseases.

关键词： caloric restriction gut microbiota metabolome

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代谢组扩展生物学的“旁中心法则”——对理解基因组学-糖组学-代谢组学-表观基因组学互作的意义

Albert Stuart Reece

《工程（英文）》 2023年第26卷第7期页码 16-16 doi: 10.1016/j.eng.2022.07.011

摘要：

The central dogma of biology holds that the transcription of DNA into RNA and the translation of RNA into proteins forms the primary axis of biological activity [1]. Following major advances in the description of the complex glycan and lipid chains that are added onto these basic building blocks, the glycome and lipidome have recently been added to this doctrine as an exciting new extension named the ‘‘paracentral dogma” [2]. However, it has been pointed out that biological systems can include many layers, which are described in modern omics technology platforms relating to both cell-intrinsic and cell-extrinsic layers of control, including metabolomic, microbiomic, immunological, epigenomic, epitranscriptomic, proteomic and phosphoproteomic layers [3].

It is well known that stem and progenitor cells have a metabolism that is based on glycolysis and glutaminolysis [4]. Although this provides less energy to the cell than oxidative phosphorylation, it suffices for these cells’ needs, since such cells are generally relatively quiescent and normally suppress energy-intensive processes such as genome duplication and transcription. Moreover, it has been shown that the high intracellular lactate levels involved in such states not only inhibits the key gatekeeper enzymes of oxidative phosphorylation (i.e., pyruvate dehydrogenase and carnitine palmitoyl acyltransferase) but also actually covalently modifies them by lactylation in order to maintain this inhibited metabolic–epigenomic state [5]. In addition, intermediate metabolism and nutrients are the source of the very extensive library of post-translational modifications to DNA, RNA, and proteins, as well as supplying cellular energy for many of the required reactions. Hence, the metabolic state locks in and reinforces the epigenomic state, and the metabolome and epigenome thereby play mutually reinforcing roles. This self-reinforcing coordination explains why it is so difficult to generate induced pluripotent cells and is a contributory explanation for why the described protocols typically have such low cellular yields.

These concepts become even more important when it is considered that cancer cells are de-differentiated, similarly rely on glycolysis and glutaminolysis, and are similarly metabolically–epigenomically–genomically synchronized. The disruption of this metabolic system is a key focus of mechanistic cancer research.

These important considerations imply that the descriptive and predictive power of the newly described ‘‘paracentral dogma” of biology may be usefully and meaningfully extended by including the metabolome, along with the genome, transcriptome, proteome, glycome, and lipidome, to describe cell-intrinsic regulation—not only in terms of another omics analytical layer but also as a fully predictive and interactive partner in the symphonic-like multilayer coordination that evidently comprises cellular regulatory layering.

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通过原位观察揭示人体肠道微生物组的重建和动态变化 Article

刘小林, 戴敏, Yue Ma, 赵娜, Ziyu Wang, Ying Yu, Yakun Xu, Huijie Zhang, Liyuan Xiang, He Tian, 税光厚, 张发明, 王军

《工程（英文）》 2022年第15卷第8期页码 89-101 doi: 10.1016/j.eng.2021.03.015

摘要：

人体肠道微生物组主要通过使用粪便样本进行研究，这种做法已经得到了关于胃肠道微生物群落的组成和功能的重要知识。然而，这种对粪便材料的依赖限制了对胃肠道其他位置（原位）微生物动力学的研究，并且粪便样本不能随时获得，这也阻碍了在更精细的时间尺度（如小时）下进行分析。在我们的研究中，我们利用结肠途径经内镜肠内导管（一种最初为粪便微生物群移植开发的技术）每天两次对回盲部微生物组进行采样；然后对这些样品进行宏基因组和宏转录组学分析。从5 名健康志愿者身上共收集了43 份回盲部样本及28 份尿液和粪便样本。在5 名志愿者中分析的回盲部和粪便微生物组被发现在宏基因组分析中相似，但它们的活性基因（宏转录组）被发现高度不同。两种微生物组在泻药暴露后都受到干扰；随着时间的推移，它们表现出与治疗前状态的差异减少，从而证明了作为肠道微生物组的先天特性——恢复力，尽管它们在我们的观察时间窗口内没有完全恢复。白天和夜间对回盲部微生物组的采样显示，在一系列细菌种类和功能途径中存在昼夜节律，特别是与短链脂肪酸产生相关的细菌，如痤疮丙酸杆菌和辅酶A生物合成II。自相关分析和波动分解进一步表明了昼夜振荡的显著周期性。粪便和尿液样本中的代谢组学分析反映出了肠道微生物组的扰动和恢复，表明肠道微生物组对参与宿主健康的诸多关键代谢物的重要贡献。这项研究为人体肠道微生物组及其内在恢复力和昼夜节律以及这些对宿主的潜在后果提供了新的见解。

关键词：昼夜节律重建宏基因组宏转录组代谢组经内窥镜肠管

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多组学联用揭示花粉过敏基于肠道菌的新机制 Article

韩珮, 李丽莎, 王子熹, 锡琳, 于航, 丛林, 张正威, 符洁, 彭冉, 潘利斌, 马殊荣, 王学艳, 王洪田, 王向东, 王琰, 孙劲旅, 蒋建东

《工程（英文）》 2022年第15卷第8期页码 115-125 doi: 10.1016/j.eng.2021.03.013

摘要：

由于过敏性疾病在世界范围内流行且尚无治愈方法，因此有必要探讨其病理生理机制。由于过敏性疾病与肠道菌群失调相关，本研究从宿主与微生物的分子层面，结合代谢组学和微生物组学，寻找可能的机制。本研究对SD大鼠注射青蒿花粉提取物以诱导其对花粉的过敏反应，这种过敏反应降低了血液中的缬氨酸、异亮氨酸、天门冬氨酸、谷氨酸、谷氨酰胺、吲哚丙酸和肌醇浓度，并减少了粪便中的短链脂肪酸（SCFA）。来自于瘤胃球菌科（Ruminococcaceae）、毛螺菌科（Lachnospiraceae）和梭状芽孢杆菌（Clostridiales）的几个有益菌属在模型组中表达减少，而幽门螺杆菌Helicobacter 和阿克曼氏菌Akkermansia 仅在模型组中表达。此外，模型组肠道claudin-3 和肝脏脂肪酸结合蛋白表达下调，与代谢变化和细菌有关。本文的研究结果表明，氨基酸及其衍生物（尤其是缬氨酸和色氨酸的还原产物吲哚丙酸）、短链脂肪酸和肠道微生物（特别是幽门螺杆菌Helicobacter 和阿克曼氏菌Akkermansia）的改变可能通过抑制claudin蛋白表达和影响黏液层而破坏肠道屏障功能，进而导致花粉过敏。

关键词：代谢组学肠道菌群花粉过敏过敏性疾病肠道屏障功能紊乱