Microbiome and metabolome features of the cardiometabolic disease spectrum.
Microbiome and metabolome features of the cardiometabolic disease spectrum.
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心脏代谢疾病谱的微生物组和代谢组特征。
DOI：
10.1038/s41591-022-01688-4
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发表时间：
2022-03
期刊：
影响因子：
82.9
通讯作者：
Pedersen O
中科院分区：
文献类型：
--
作者：
Fromentin S;Forslund SK;Chechi K;Aron-Wisnewsky J;Chakaroun R;Nielsen T;Tremaroli V;Ji B;Prifti E;Myridakis A;Chilloux J;Andrikopoulos P;Fan Y;Olanipekun MT;Alves R;Adiouch S;Bar N;Talmor-Barkan Y;Belda E;Caesar R;Coelho LP;Falony G;Fellahi S;Galan P;Galleron N;Helft G;Hoyles L;Isnard R;Le Chatelier E;Julienne H;Olsson L;Pedersen HK;Pons N;Quinquis B;Rouault C;Roume H;Salem JE;Schmidt TSB;Vieira-Silva S;Li P;Zimmermann-Kogadeeva M;Lewinter C;Søndertoft NB;Hansen TH;Gauguier D;Gøtze JP;Køber L;Kornowski R;Vestergaard H;Hansen T;Zucker JD;Hercberg S;Letunic I;Bäckhed F;Oppert JM;Nielsen J;Raes J;Bork P;Stumvoll M;Segal E;Clément K;Dumas ME;Ehrlich SD;Pedersen O
之前探索非传染性疾病的微生物组和代谢组分析很少关注研究结果的主要混杂因素，例如常见的、病前的和共病的情况，或多药治疗。在这里，在缺血性心脏病 (IHD) 的背景下，我们使用了一种研究设计，该设计可以概括疾病的发生、升级和随着时间的推移对治疗的反应，反映了一项纵向研究，鉴于 IHD 发病机制的长期性质，否则该研究很难进行。我们招募了 1,241 名中年欧洲人，包括健康个体、患有代谢障碍疾病（肥胖和 2 型糖尿病）但缺乏明显 IHD 诊断的个体，以及处于三个不同临床阶段（急性冠状动脉综合征、慢性 IHD 和心力衰竭的 IHD）的 IHD 个体，并表征了他们的表型组、肠道宏基因组以及血清和尿液代谢组。我们发现，在调整药物和生活方式的影响后，约 75% 的微生物组和代谢组特征存在于表现出代谢障碍的个体中，这表明肠道微生物组和代谢组的重大改变可能早在 IHD 临床发病之前就开始了。我们进一步对与前驱代谢障碍相关的微生物组和代谢组特征进行了分类，这些特征针对一般 IHD 或其三种亚型中的每一种，或者与 IHD 的升级或降级相关。与传统风险标记相比，基于特定 IHD 微生物组和代谢组特征的判别分析可以更好地将 IHD 个体与健康个体或代谢匹配个体区分开来，指出这些特征的病理生理学相关性。通过研究患有一系列心脏代谢疾病的个体并调整生活方式和药物的影响，这项研究确定了从肥胖和 2 型糖尿病等代谢失调状况到缺血性心脏病的代谢组和微生物组的变化。
Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features. By studying individuals along a spectrum of cardiometabolic disease and adjusting for effects of lifestyle and medication, this investigation identifies alterations of the metabolome and microbiome from dysmetabolic conditions, such as obesity and type 2 diabetes, to ischemic heart disease.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
6
作者：
Dona AC;Kyriakides M;Scott F;Shephard EA;Varshavi D;Veselkov K;Everett JR
通讯作者：
Everett JR
影响因子：
20.1
作者：
Kelly TN;Bazzano LA;Ajami NJ;He H;Zhao J;Petrosino JF;Correa A;He J
通讯作者：
He J
影响因子：
2.2
作者：
Hunter, Ingrid;Rehfeld, Jens F.;Goetze, Jens P.
通讯作者：
Goetze, Jens P.
影响因子：
8.6
作者：
Dehaven CD;Evans AM;Dai H;Lawton KA
通讯作者：
Lawton KA