Integration of constraint-based modeling with fecal metabolomics reveals large deleterious effects of Fusobacterium spp. on community butyrate production.
Integration of constraint-based modeling with fecal metabolomics reveals large deleterious effects of Fusobacterium spp. on community butyrate production.
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DOI：
10.1080/19490976.2021.1915673
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发表时间：
2021-01
期刊：
影响因子：
12.2
通讯作者：
Thiele I
中科院分区：
文献类型：
--
作者：
Hertel J;Heinken A;Martinelli F;Thiele I
表征肠道微生物组在健康和疾病中的代谢功能对于将微生物组成的变化转化为临床见解至关重要。两种主要的分析范式已被用来探索微生物组的代谢功能，但并未系统地相互整合：统计筛选方法，例如代谢组-微生物组关联研究，以及计算方法，例如基于约束的代谢模型。为了结合两种分析范式的优势，我们在此引入了一组理论概念，允许对基于约束的微生物群落模型进行群体统计处理。为了证明该理论框架的实用性，我们将其应用于由 365 例结直肠癌 (CRC) 病例和 251 例健康对照组成的公共宏基因组数据集，揭示了梭杆菌属的代谢作用。在CRC中。我们发现（1）CRC微生物组中戊二酸的生产能力显着富集，并且与梭杆菌属中的赖氨酸发酵存在机制上的联系；（2）CRC中乙酸和丁酸的生产潜力降低；（3）梭杆菌属中的乙酸和丁酸生产潜力降低。在 CRC 病例和健康对照中，存在对社区丁酸盐生产产生巨大的负面生态影响。根据粪便代谢组学验证模型预测，计算机框架以高精度正确预测了体内物种代谢物相关性。总之，本研究强调了将统计关联研究与计算机建模相结合的价值，为梭杆菌属的代谢作用提供了见解。在肠道中，同时为基于约束的微生物群落建模的有效性提供概念证明。
Characterizing the metabolic functions of the gut microbiome in health and disease is pivotal for translating alterations in microbial composition into clinical insights. Two major analysis paradigms have been used to explore the metabolic functions of the microbiome but not systematically integrated with each other: statistical screening approaches, such as metabolome-microbiome association studies, and computational approaches, such as constraint-based metabolic modeling. To combine the strengths of the two analysis paradigms, we herein introduce a set of theoretical concepts allowing for the population statistical treatment of constraint-based microbial community models. To demonstrate the utility of the theoretical framework, we applied it to a public metagenomic dataset consisting of 365 colorectal cancer (CRC) cases and 251 healthy controls, shining a light on the metabolic role of Fusobacterium spp. in CRC. We found that (1) glutarate production capability was significantly enriched in CRC microbiomes and mechanistically linked to lysine fermentation in Fusobacterium spp., (2) acetate and butyrate production potentials were lowered in CRC, and (3) Fusobacterium spp. presence had large negative ecological effects on community butyrate production in CRC cases and healthy controls. Validating the model predictions against fecal metabolomics, the in silico frameworks correctly predicted in vivo species metabolite correlations with high accuracy. In conclusion, highlighting the value of combining statistical association studies with in silico modeling, this study provides insights into the metabolic role of Fusobacterium spp. in the gut, while providing a proof of concept for the validity of constraint-based microbial community modeling.
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影响因子：
11
作者：
Carr, Alex;Diener, Christian;Gibbons, Sean M.
通讯作者：
Gibbons, Sean M.
影响因子：
4.8
作者：
Flynn KJ;Baxter NT;Schloss PD
通讯作者：
Schloss PD
一种简单而新颖的结直肠癌粪便生物标志物：具核梭杆菌与益生菌群的比例，基于其拮抗作用。
影响因子：
9.3
作者：
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通讯作者：
Zhang, Ge
影响因子：
14.8
作者：
Heirendt, Laurent;Arreckx, Sylvain;Fleming, Ronan M. T.
通讯作者：
Fleming, Ronan M. T.
影响因子：
5.8
作者：
Baldini, Federico;Heinken, Almut;Thiele, Ines
通讯作者：
Thiele, Ines