Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes
Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes
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DOI：
10.1186/s40168-019-0631-8
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发表时间：
2019-02-11
期刊：
影响因子：
15.5
通讯作者：
Hettich, Robert L.
中科院分区：
文献类型：
--
作者：
Blakeley-Ruiz, J. Alfredo;Erickson, Alison R.;Hettich, Robert L.
背景肠道微生物组通过贡献关键的生物学功能（如扩展的代谢和病原体防御/免疫控制）在人类宿主的整体健康中起着基础性作用。在健康个体中，肠道微生物组以共生、非炎症的关系共存于人类宿主内，这使得双方都受益，例如将难消化的食物产品微生物降解成宿主可以利用的小分子，以及增强病原体防御。在异常情况下，如克罗恩病，这种有利的代谢关系被打破，并导致各种不良活动，包括慢性炎症和其他健康相关问题。然而，很难阐明这种关系的总体功能特征，因为健康人的微生物群组成可能差异很大，在患有肠道疾病如克罗恩病的个体中可能甚至更多。总的来说，这表明微生物成员组成可能不是表征表型的最佳方式。或者，检查和表征肠道微生物组的功能组成似乎更具信息性。为此，本研究检查了在几名克罗恩病患者的切除手术后1年内测量的25个元蛋白质组，以检查微生物分类群，基因，蛋白质和代谢功能分布随时间的持续性，这些个体的微生物组可能由于肠道疾病状况而更具可变性。所有的时间相关的元蛋白质组通过个体最紧密地聚类。一般来说，元蛋白质组在个体之间和个体内的程度较小。这促使需要在更高的功能水平上表征元蛋白质组，这是通过用KEGG直链淀粉组注释鉴定的蛋白质组来推断代谢模块来实现的。在这个水平上，在不同时间和不同个体之间观察到多个门的相似和冗余的代谢功能。通过这些不同的代谢模块跟踪揭示了一个明确的路径，从碳水化合物，脂质和氨基酸的降解，中央代谢，最后生产的发酵products.ConclusionsThe人肠道元蛋白质组可以在很大程度上不同的时间和个人。然而，尽管大量的个体内变异的元蛋白质组，有一个明确的持久性保守的代谢功能，跨时间和个人。此外，这些核心功能的持久性在多个门中是冗余的，但在同一样本中并不总是可观察到的。最后，肠道微生物组的代谢不是由一组离散的线性途径驱动的，而是由一个酶网络促进的相互连接的反应网络，该酶网络将多个分子连接在多个途径上。
BackgroundThe gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn's disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn's disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn's disease patients' post-resection surgery across the course of 1year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition.ResultsThe measured metaproteomes were highly personalized, with all the temporally-related metaproteomes clustering most closely by individual. In general, the metaproteomes were remarkably distinct between individuals and to a lesser extent within individuals. This prompted a need to characterize the metaproteome at a higher functional level, which was achieved by annotating identified protein groups with KEGG orthologous groups to infer metabolic modules. At this level, similar and redundant metabolic functions across multiple phyla were observed across time and between individuals. Tracking through these various metabolic modules revealed a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products.ConclusionsThe human gut metaproteome can vary quite substantially across time and individuals. However, despite substantial intra-individual variation in the metaproteomes, there is a clear persistence of conserved metabolic functions across time and individuals. Additionally, the persistence of these core functions is redundant across multiple phyla but is not always observable in the same sample. Finally, the gut microbiome's metabolism is not driven by a set of discrete linear pathways but a web of interconnected reactions facilitated by a network of enzymes that connect multiple molecules across multiple pathways.