肠道菌群及联用组学技术在中药领域上的研究进展

肠道菌群与各脏器相关联,能够反映中医药整体观特点。肠道菌群在中药作用机制、配伍应用和毒理等领域广泛应用。中药可影响肠道菌群数量和组成,改善肠菌丰度和多样性,同时肠道菌群也可代谢转化中药活性成分,与中药相互影响,促进中药药效发挥。肠道菌群联合代谢组学等多组学技术通过多层次分析,有利于全面阐释肠道菌群与中药作用机制。本文利用数据库综合检索近十年发表的相关文献,阐释肠道菌群和中药之间的相互作用,归纳总结肠道菌群在中药药效、配伍、炮制、毒理领域的研究进展以及与代谢组学等多组学技术联合应用,为深入研究肠道菌群和中药之间的关系及多组学技术在肠道菌群与中药之间的应用提供理论依据和参考。     

多组学在慢性病病因学研究中的应用及其进展

慢性病流行病学的主要目的之一是探索疾病病因。多组学通常包括在脱氧核糖核酸复制、转录、翻译、翻译后修饰的过程中,产生的全部基因(基因组学)、基因表达的广泛变化(表观遗传组学)、核糖核酸(转录组学)和蛋白质(蛋白质组学),以及下游的小分子代谢产物(代谢组学)。多组学检测技术为包括基因组、转录组、蛋白质组在内的组学测定提供技术支持,系统流行病学为利用多组学开展病因研究提供理论与方法支持。多组学研究既揭示了分子间的相互作用网络,又从微观病因学层面有助于因果推断。随着国际公开数据、分析平台与协作组的指数级增长,多组学研究资源将更加丰富,所研究的深度与广度也将得到大幅扩展。本文将详细介绍多组学在慢性病病因学研究中的应用及近三年的研究进展、多组学对慢性病流行病学研究的意义和价值、为大规模队列研究带来的机遇与挑战、中国在多组学病因学研究的优势与问题及多组学研究展望。     

Network Analysis in Systems Epidemiology

Traditional epidemiological studies have identified a number of risk factors for various diseases using regression-based methods that examine the association between an exposure and an outcome (i.e., one-to-one correspondences). One of the major limitations of this approach is the “black-box” aspect of the analysis, in the sense that this approach cannot fully explain complex relationships such as biological pathways. With high-throughput data in current epidemiology, comprehensive analyses are needed. The network approach can help to integrate multi-omics data, visualize their interactions or relationships, and make inferences in the context of biological mechanisms. This review aims to introduce network analysis for systems epidemiology, its procedures, and how to interpret its findings.     

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC–Q-TOF/MS, LC–MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.     

Gut microbiota dysbiosis in stable coronary artery disease combined with type 2 diabetes mellitus influences cardiovascular prognosis

Background and aimsHost–microbiota interactions involving metabolic pathways have been linked to the pathogenesis of atherosclerotic disease and type 2 diabetes. As stable coronary artery disease (SCAD) patients combined with type 2 diabetes have significantly increased risk for cardiac event, we focused on elucidating the role of microbiota affecting cardiometabolic disease development.Methods and resultsWe used multi-omics analyses (metagenomics and metabolomics) of fecal and serum samples from a prospective cohort including stable coronary artery disease combined with diabetes mellitus (SCAD + T2DM, n = 38), SCAD (n = 71), and healthy control (HC, n = 55). We linked microbiome features to disease severity in a three-pronged association analysis and identified prognostic bacterial biomarkers. We identified that bacterial and metabolic signatures varied significantly between SCAD and SCAD + T2DM groups. SCAD + T2DM individuals were characterized by increased levels of aromatic amino acids and carbohydrates, which correlate with a gut microbiome with enriched biosynthetic potential. Our study also addressed how metformin may confound gut dysbiosis and increase the potential for nitrogen metabolism. In addition, we found that specific bacterial taxa Ruminococcus torques [HR: 2.363 (08–4.56), P = 0.03] was predictive of cardiac survival outcomes.ConclusionOverall, our study identified relationships between features of the gut microbiota (GM) and circulating metabolites, providing a new direction for future studies aiming to understand the host–GM interplay in atherosclerotic cardiovascular pathogenesis.     

基因组、转录组及表观基因组在肺癌中的联合分析CSCD

随着以第二代测序技术为代表的高通量测序技术的快速发展,当前全基因组检测技术可以检测到基因组、转录组和表观基因组等多个层面的数据。生命体是一个复杂的调控系统,涉及诸多层次的复杂调控机制,基于单一组学数据分析致病因子显得局限,而通过各组学之间线性或非线性关系等可以将三者联系在一起,进而对多组学数据进行整合分析,为疾病研究提供新的思路。多组学联合分析广泛应用于各疾病邻域,在肺癌中也已有较多研究,而DNA或基因分子水平作为分子之间关联和复杂网络研究的基础尤为重要,因此本文就肺癌的基因组、转录组及表观基因组三个基于基因水平组学的联合研究进展作简要综述。     

Assessing capreomycin resistance on tlyA deficient and point mutation (G695A) Mycobacterium tuberculosis strains using multi-omics analysis

Capreomycin (CAP), a cyclic peptide antibiotic, is considered to be an ideal second-line drug for tuberculosis (TB). However, in the past few years, the emergence of more CAP-resistant (CAP^r) TB patients has limited its use. Although it has been reported that CAP resistance to Mycobacterium tuberculosis (Mtb) is associated with rrs or tlyA mutation, the exact mechanism of CAP^r Mtb strains, especially the mechanism associated with tlyA deficient or mutation, is not fully understood. Herein, we utilized a multi-omics (genome, proteome, and metabolome) approach to assess CAP resistance on tlyA deficient CAP^r Mtb strains (CAP^r1) and tlyA point mutation CAP^r Mtb strains (CAP^r2) that we established for the first time in vitro to investigate the CAP-resistant mechanism. Our results showed that the CAP^r1 strains (> 40 μg/ml) was more resistant to CAP than the CAP^r2 strains (G695A, 10 μg/ml). Furthermore, multi-omics analysis indicated that the CAP^r1 strains exhibited greater drug tolerance than the CAP^r2 strains may be associated with the weakening of S-adenosyl-L-methionine-dependent methyltransferase (AdoMet-MT) activity and abnormal membrane lipid metabolism such as suppression of fatty acid metabolism, promotion of glycolipid phospholipid and glycerolipid metabolism. As a result, these studies reveal a new mechanism for CAP resistance to tlyA deficient or mutation Mtb strains, and may be helpful in developing new therapeutic approaches to prevent Mtb resistance to CAP.     

组学技术在中药种质资源遗传评价与创新中的应用＊

中药种质资源的评价与创新是现代中医药产业发展的基础。随着基因组学等前沿学科的发展，多组学整合分析已经成为现代作物种质资源遗传评价的重要手段。本文系统综述了组学技术在中药种质资源鉴定评价、核心种质筛选、基因资源挖掘和新品种选育等方面的应用，并以笔者所在的湖北省为例，列举了代表性中药资源类群的相关研究案例，以期为未来中药源头产业的高质量发展探讨技术引领的方向和思路，并为我国区域性中药种质资源的保护、评价和应用提供参考。