Microbiome：宏蛋白质组揭示健康人肠道菌群的功能，离真相更近了一步
众所周知，目前研究宏基因组最常用方法的是扩增子、和全基因组测序。虽然方法简单高效，但缺点也是显示易见的。比如只针对DNA为研究对象，这样无法判断研究对像是否还活着，连上百万年的化石都会有DNA保存下来可以测序。
近年来宏转录组的应用，让我们离真相近了一步，因为RNA半衰期短，更能反应当前菌群的活性和功能。
在模式生物研究中，转录组和蛋白组有较多的数据积累，有Sciences文章大规模分析表明：蛋白水平与转录水平的相关性很低，远超大家的想象。
而本文中，采用宏蛋白组，研究健康人类肠道菌群的功能，是离真相更近了一步，推荐阅读。
健康人群肠道菌群的潜能及活性功能
背景
采用各类鸟枪法的宏组学，肠道菌群的研究正快速向功能解析前进。在此背景下，人类肠道生理条件下微生物功能的组成型表达结果仍不清楚。本研究采用16个健康个体为对象，采用宏蛋白组学方法研究健康人群中肠道菌群表达的真实功能。此外，本研究的结果可进一步与已知的宏基因组和细菌分类学结果进行比较分析。
结果
宏基因组和宏蛋白组的数据关于物种分类水平上比较一致。另一方面，个体的遗传背景和功能活性差别还是很明显的，波动范围大于宏基因组的结果，表现为更高的可塑性。对分类学某类特异菌贡献功能活性或代谢物的分析，发现某些类菌特异的碳水化合物代谢活性，如多糖降解、多糖转运、糖酵解、短链脂肪酸生成等。厚壁菌门中主要是Faecalibacterium促进丁酸盐合成有着最高的表达率及代谢活性，个体间差异最小。此类物质在以前研究中报导为重要的微生物产物并维持肠道的动态平衡。
结论
本文的结果提供了健康人体肠道菌群中物种类型关于功能途径活性的详细信息。对宏基因中发现的潜在功能与宏蛋白组的表达功能进行差别比较，表明从宏基因组层面上发现的功能下结论，最好有宏蛋白组的结果支持其代谢物的功能和活性。
英文摘要
Potential and active functions in the gut microbiota of a healthy human cohort
Background
The study of the gut microbiota (GM) is rapidly moving towards its functional characterization by means of shotgun meta-omics. In this context, there is still no consensus on which microbial functions are consistently and constitutively expressed in the human gut in physiological conditions. Here, we selected a cohort of 15 healthy subjects from a native and highly monitored Sardinian population and analyzed their GMs using shotgun metaproteomics, with the aim of investigating GM functions actually expressed in a healthy human population. In addition, shotgun metagenomics was employed to reveal GM functional potential and to compare metagenome and metaproteome profiles in a combined taxonomic and functional fashion.
Results
Metagenomic and metaproteomic data concerning the taxonomic structure of the GM under study were globally comparable. On the contrary, a considerable divergence between genetic potential and functional activity of the human healthy GM was observed, with the metaproteome displaying a higher plasticity, compared to the lower inter-individual variability of metagenome profiles. The taxon-specific contribution to functional activities and metabolic tasks was also examined, giving insights into the peculiar role of several GM members in carbohydrate metabolism (including polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production). Noteworthy, Firmicutes-driven butyrogenesis (mainly due to Faecalibacterium spp.) was shown to be the metabolic activity with the highest expression rate and the lowest inter-individual variability in the study cohort, in line with the previously reported importance of the biosynthesis of this microbial product for the gut homeostasis.
Conclusions
Our results provide detailed and taxon-specific information regarding functions and pathways actively working in a healthy GM. The reported discrepancy between expressed functions and functional potential suggests that caution should be used before drawing functional conclusions from metagenomic data, further supporting metaproteomics as a fundamental approach to characterize the human GM metabolic functions and activities.
Reference
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0293-3
http://www.xunludkp.com/papers/read/1062284580?kf=xread_daily
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