Colonic Butyrate-Producing Communities in Humans: an Overview Using Omics Data.
Colonic Butyrate-Producing Communities in Humans: an Overview Using Omics Data.
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DOI：
10.1128/msystems.00130-17
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发表时间：
2017-11
期刊：
影响因子：
6.4
通讯作者：
Pieper DH
中科院分区：
文献类型：
--
作者：
Vital M;Karch A;Pieper DH
关于肠道微生物区系的分类组成的研究很多，但对其功能仍知之甚少。具体的关键功能值得详细研究，因为它们调节微生物群与宿主的相互作用，并促进宿主健康和疾病。丁酸盐的生产是首要目标之一，因为这种微生物衍生的代谢物的耗尽与几种新出现的非传染性疾病有关，并被证明通过破坏定植抗性来促进肠道病原体的建立。在这项研究中，我们建立了一个工作流程，从组学数据中提取其生化和分类多样性，详细调查多门产丁酸群落的组成。通过结合来自各种公开可用的数据集的信息，我们确定了这一功能组的普遍生态关键特征，并阐明了它在健康和疾病中的作用。我们的研究结果将有助于精准医学的发展，以对抗功能性生物失调。鉴于丁酸盐对宿主健康的关键作用，了解肠道丁酸盐产生群落的生态是肠道微生物区系研究的重中之重。为此，我们对来自15个公开可用的数据集的2387个元基因组/转录组样本进行了汇集分析，这些数据集来自三个大陆，涵盖了八种疾病以及特定的干预措施。为了进行分析，从所有样品的丁酸合成途径中的所有基因的基因靶向组装和来自基因组筛选的最新参考数据库构建了基因目录。我们证明，丁酸盐生产者在生命的第一年就确立了自己的地位，并在成年人中表现出高丰度(>；占总细菌群落的20%)，无论来源如何。不同的细菌组成了这个功能群，表现出包括不同途径和终止酶的生化多样性，其中一个以碳水化合物为燃料的途径占主导地位，丁酰辅酶A(CoA)：乙酸辅酶A转移酶是主要的终止酶。受试者表现出高度丰富的丁酸产生菌，在70%的个体中检测到17个分类群，主要是乳螺科和反刍球菌科的成员，以及一些拟杆菌，涵盖了丁酸生产总潜力的约85%。这些关键分类群中的大多数也被发现表达丁酸形成的基因，这表明丁酸生产者在肠道生态系统中占据着不同的生态位，同时合成这种化合物。此外，纵向分析的结果表明，在日常生活干扰和抗生素治疗等干预期间，多样性支持功能稳定性。在各种疾病中检测到丁酸生产潜力的减少以及社区的改变，其中患有心脏代谢障碍的患者受到的影响特别大。重点研究肠道微生物区系的分类组成的重要性研究很多，但对其功能仍知之甚少。具体的关键功能值得详细研究，因为它们调节微生物群与宿主的相互作用，并促进宿主健康和疾病。丁酸盐的生产是首要目标之一，因为这种微生物衍生的代谢物的耗尽与几种新出现的非传染性疾病有关，并被证明通过破坏定植抗性来促进肠道病原体的建立。在这项研究中，我们建立了一个工作流程，从组学数据中提取其生化和分类多样性，详细调查多门产丁酸群落的组成。通过结合来自各种公开可用的数据集的信息，我们确定了这一功能组的普遍生态关键特征，并阐明了它在健康和疾病中的作用。我们的研究结果将有助于精准医学的发展，以对抗功能性生物失调。
Studies focusing on taxonomic compositions of the gut microbiota are plentiful, whereas its functional capabilities are still poorly understood. Specific key functions deserve detailed investigations, as they regulate microbiota-host interactions and promote host health and disease. The production of butyrate is among the top targets since depletion of this microbe-derived metabolite is linked to several emerging noncommunicable diseases and was shown to facilitate establishment of enteric pathogens by disrupting colonization resistance. In this study, we established a workflow to investigate in detail the composition of the polyphyletic butyrate-producing community from omics data extracting its biochemical and taxonomic diversity. By combining information from various publicly available data sets, we identified universal ecological key features of this functional group and shed light on its role in health and disease. Our results will assist the development of precision medicine to combat functional dysbiosis. Given the key role of butyrate for host health, understanding the ecology of intestinal butyrate-producing communities is a top priority for gut microbiota research. To this end, we performed a pooled analysis on 2,387 metagenomic/transcriptomic samples from 15 publicly available data sets that originated from three continents and encompassed eight diseases as well as specific interventions. For analyses, a gene catalogue was constructed from gene-targeted assemblies of all genes from butyrate synthesis pathways of all samples and from an updated reference database derived from genome screenings. We demonstrate that butyrate producers establish themselves within the first year of life and display high abundances (>20% of total bacterial community) in adults regardless of origin. Various bacteria form this functional group, exhibiting a biochemical diversity including different pathways and terminal enzymes, where one carbohydrate-fueled pathway was dominant with butyryl coenzyme A (CoA):acetate CoA transferase as the main terminal enzyme. Subjects displayed a high richness of butyrate producers, and 17 taxa, primarily members of the Lachnospiraceae and Ruminococcaceae along with some Bacteroidetes, were detected in >70% of individuals, encompassing ~85% of the total butyrate-producing potential. Most of these key taxa were also found to express genes for butyrate formation, indicating that butyrate producers occupy various niches in the gut ecosystem, concurrently synthesizing that compound. Furthermore, results from longitudinal analyses propose that diversity supports functional stability during ordinary life disturbances and during interventions such as antibiotic treatment. A reduction of the butyrate-producing potential along with community alterations was detected in various diseases, where patients suffering from cardiometabolic disorders were particularly affected. IMPORTANCE Studies focusing on taxonomic compositions of the gut microbiota are plentiful, whereas its functional capabilities are still poorly understood. Specific key functions deserve detailed investigations, as they regulate microbiota-host interactions and promote host health and disease. The production of butyrate is among the top targets since depletion of this microbe-derived metabolite is linked to several emerging noncommunicable diseases and was shown to facilitate establishment of enteric pathogens by disrupting colonization resistance. In this study, we established a workflow to investigate in detail the composition of the polyphyletic butyrate-producing community from omics data extracting its biochemical and taxonomic diversity. By combining information from various publicly available data sets, we identified universal ecological key features of this functional group and shed light on its role in health and disease. Our results will assist the development of precision medicine to combat functional dysbiosis.