Université de Toulouse, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse cedex, France.
Curr Pharm Biotechnol. 2012 Apr;13(5):746-58. doi: 10.2174/138920112799857567.
Over the last five years an increasing effort has been made to understand the role of intestinal microbiota in health and disease, resulting in regarding to it as a new organ actively involved in the control of host metabolism, both in humans and mice. Amongst hundreds (up to thousand) germ species inhabiting the intestine, few of them are cultivable. Nevertheless, next-generation sequencing-based molecular technologies have been developed, allowing to overcome this problem and shed light on the way the gut microbiota undergoes dramatic changes during (patho)-physiological modifications of the host. Hence, the study of the overall gut germ genome (metagenome) and transcriptome (microbiome) has been launched. Thus, Genomics and Transcriptomics have begun to be increasingly used, opening the so called "Omics" era, including Proteomics and Metabolomics techniques as well. Taken together, the "Omics" allow the study of gut microbiota impact on whole host metabolism, resulting in the definition of new metabolic profiles (i.e. the presence of metabolites within the blood defines a metabolomic profile), others than those based on nucleic acid analyses only. Once demonstrated the involvement of gut microbiota within metabolic diseases, "Omics" analyses has allowed the identification of the obesity-induced gut microbiota imbalance, characterized by increased Firmicutes to Bacteroidetes ratio (metagenomics) and of the so called "core microbiome", focusing on the gut microbiota at a gene- rather than, solely, at a taxonomic-level. In addition, metabolomics studies revealed, for instance, the implication of gut microbiota to nonalcoholic fatty liver disease in insulin-resistant mice. Additionally, the use of germ-free (axenic) mice has made possible the microflora transfer to investigate the mechanisms through which gut microbes modulate host metabolism, albeit the molecular actors of the host� � � gut-microbiota interplay remain to be fully determined. Here, we report the role of "Omics" in the multiple analyses of gut microbiota-driven metabolic modifications of the host, proposing also to focus on lipopolysaccharides (LPS), the Gram negative proinflammatory molecules we already showed to be the initiators of metabolic diseases.
在过去的五年中，人们越来越努力地了解肠道微生物群在健康和疾病中的作用，因此将其视为一个积极参与宿主代谢控制的新器官，这在人类和小鼠中都是如此。在栖息于肠道的数百（多达千）种细菌中，只有少数几种可培养。然而，基于下一代测序的分子技术已经被开发出来，使得人们能够克服这个问题，并揭示肠道微生物群在宿主（病理）生理改变过程中发生剧烈变化的方式。因此，人们已经开始研究肠道总细菌基因组（宏基因组）和转录组（微生物组）。因此，基因组学和转录组学开始被越来越多地使用，开创了所谓的“组学”时代，包括蛋白质组学和代谢组学技术。综上所述，“组学”允许研究肠道微生物群对宿主整体代谢的影响，从而定义新的代谢谱（即血液中代谢物的存在定义了代谢组学谱），而不仅仅是基于核酸分析的谱。一旦证明肠道微生物群参与代谢性疾病，“组学”分析就允许确定肥胖引起的肠道微生物群失衡，其特征是厚壁菌门与拟杆菌门的比例增加（宏基因组学）和所谓的“核心微生物群”，其重点是肠道微生物群的基因水平，而不仅仅是分类学水平。此外，代谢组学研究表明，例如，肠道微生物群在胰岛素抵抗小鼠的非酒精性脂肪性肝病中的作用。此外，使用无菌（无菌）小鼠使得可以进行微生物转移，以研究肠道微生物群调节宿主代谢的机制，尽管宿主-肠道微生物群相互作用的分子因子仍有待完全确定。在这里，我们报告了“组学”在分析宿主肠道微生物群驱动的代谢修饰中的作用，还建议集中研究脂多糖（LPS），即革兰氏阴性促炎分子，我们已经表明它们是代谢性疾病的启动子。
