NMR Metabolomics Reveal Urine Markers of Microbiome Diversity and Identify Benzoate Metabolism as a Mediator between High Microbial Alpha Diversity and Metabolic Health.
NMR Metabolomics Reveal Urine Markers of Microbiome Diversity and Identify Benzoate Metabolism as a Mediator between High Microbial Alpha Diversity and Metabolic Health.
复制标题
DOI：
10.3390/metabo12040308
复制
发表时间：
2022-03-31
期刊：
影响因子：
4.1
通讯作者：
Frost, Fabian
中科院分区：
文献类型：
--
作者：
Hertel, Johannes;Faessler, Daniel;Heinken, Almut;Weiss, Frank U.;Ruehlemann, Malte;Bang, Corinna;Franke, Andre;Budde, Kathrin;Henning, Ann-Kristin;Petersmann, Astrid;Voelker, Uwe;Voelzke, Henry;Thiele, Ines;Grabe, Hans-Joergen;Lerch, Markus M.;Nauck, Matthias;Friedrich, Nele;Frost, Fabian
使用核磁共振测量的微生物代谢物可以作为生理或病理宿主-微生物相互作用的标记，并可能介导微生物组多样性的有益影响。然而，对肠道微生物组数据和来自大型普通人群的尿液核磁共振代谢组的综合分析却缺失。在这里，我们报告了肠道微生物群丰度或 α 多样性指标之间的关联，使用 16S rRNA 基因测序从粪便样本中进行量化，并与波美拉尼亚健康研究 (SHIP) 的 951 名参与者的目标尿液 NMR 代谢物测量结果进行比较。我们检测到马尿酸、琥珀酸、硫酸吲哚酚和甲酸具有显着的属-代谢物关联。此外，在复制之前报道的马尿酸与α多样性测量之间的关联的同时，我们确定甲酸和4-羟基苯乙酸盐作为肠道微生物组α多样性的新标志物。接下来，我们通过弹性网络回归方法，使用属丰度预测了每种代谢物的尿浓度。我们发现基于微生物组的马尿酸盐预测评分与肝损伤、炎症和代谢健康标志物之间存在深刻的关联。此外，基于微生物组的马尿酸盐预测评分完全介导了微生物多样性的临床关联模式，暗示苯甲酸盐代谢在高α多样性与健康状态之间的正相关性中发挥着作用。总之，大规模 NMR 尿液代谢组学为代谢宿主-微生物组相互作用提供了新的见解，确定了苯甲酸盐代谢途径作为介导高微生物 α 多样性对健康有益影响的相关候选途径。
Microbial metabolites measured using NMR may serve as markers for physiological or pathological host–microbe interactions and possibly mediate the beneficial effects of microbiome diversity. Yet, comprehensive analyses of gut microbiome data and the urine NMR metabolome from large general population cohorts are missing. Here, we report the associations between gut microbiota abundances or metrics of alpha diversity, quantified from stool samples using 16S rRNA gene sequencing, with targeted urine NMR metabolites measures from 951 participants of the Study of Health in Pomerania (SHIP). We detected significant genus–metabolite associations for hippurate, succinate, indoxyl sulfate, and formate. Moreover, while replicating the previously reported association between hippurate and measures of alpha diversity, we identified formate and 4-hydroxyphenylacetate as novel markers of gut microbiome alpha diversity. Next, we predicted the urinary concentrations of each metabolite using genus abundances via an elastic net regression methodology. We found profound associations of the microbiome-based hippurate prediction score with markers of liver injury, inflammation, and metabolic health. Moreover, the microbiome-based prediction score for hippurate completely mediated the clinical association pattern of microbial diversity, hinting at a role of benzoate metabolism underlying the positive associations between high alpha diversity and healthy states. In conclusion, large-scale NMR urine metabolomics delivered novel insights into metabolic host–microbiome interactions, identifying pathways of benzoate metabolism as relevant candidates mediating the beneficial health effects of high microbial alpha diversity.
登录
查看更多内容
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
4.1
作者：
Hirano, Atsushi;Umeno, Junji;Esaki, Motohiro
通讯作者：
Esaki, Motohiro
影响因子：
12.2
作者：
Hertel J;Heinken A;Martinelli F;Thiele I
通讯作者：
Thiele I
影响因子：
29.4
作者：
Hollister EB;Gao C;Versalovic J
通讯作者：
Versalovic J
影响因子：
4.8
作者：
Hicks, Raymond;Tingley, Dustin
通讯作者：
Tingley, Dustin