Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, 37831, USA.
Graduate School of Genome Science & Technology, University of Tennessee, Knoxville, TN, 37996, USA.
Microbiome. 2019 Feb 11;7(1):18. doi: 10.1186/s40168-019-0631-8.
The 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 1 year, 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.
The 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.
The 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.
肠道微生物组通过提供扩展代谢和病原体防御/免疫控制等关键生物学功能，在人体宿主的整体健康中发挥着根本作用。在健康个体中，肠道微生物组与人体宿主共生共存，处于非炎症性的共生关系中，从而实现互利互惠，例如微生物降解不可消化的食物产物为宿主可利用的小分子，以及增强病原体防御。然而，在异常情况下，例如克罗恩病，这种有利的代谢关系会瓦解，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，由于健康人群的微生物组在组成上可能有很大差异，甚至在患有克罗恩病等肠道疾病的个体中可能差异更大，因此很难阐明这种关系的整体功能特征。总体而言，这表明微生物成员组成可能不是表征表型的最佳方法。相反，检查和表征肠道微生物组的功能组成似乎更具信息量。为此，本研究对 25 个克罗恩病患者术后 1 年内的宏蛋白质组进行了测量，以检查在由于肠道疾病条件而微生物组可能更具变异性的个体中，微生物类群、基因、蛋白质和代谢功能分布随时间的持久性。
所测量的宏蛋白质组具有高度的个体特异性，所有与时间相关的宏蛋白质组聚类最接近个体。通常，宏蛋白质组在个体之间差异很大，在个体内部差异较小。这促使我们需要在更高的功能水平上对宏蛋白质组进行特征描述，这是通过将鉴定的蛋白质组与 KEGG 直系同源群进行注释来实现的，以推断代谢模块。在这个水平上，不同门之间的多个时间和个体都观察到了相似和冗余的代谢功能。通过这些各种代谢模块的跟踪，清楚地揭示了从碳水化合物、脂质和氨基酸降解到中心代谢，最后到发酵产物产生的途径。
人体肠道宏蛋白质组在时间和个体之间可能有很大差异。然而，尽管宏蛋白质组在个体内部有很大的变化，但在时间和个体之间仍然存在着明显的保守代谢功能的持久性。此外，这些核心功能的持久性在多个门中是冗余的，但并不总是在同一样本中观察到。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，而是由一个由连接多个分子的多个途径的酶组成的网络所促进的相互连接的反应网络。
