The gut microbiota interacts with the host via production of various metabolites of dietary nutrients. Herein, we proposed the concept of the gut microbiota-derived core nutrient metabolome, which covers 43 metabolites in carbohydrate metabolism, glycolysis, tricarboxylic acid cycle and amino acid metabolism, and established a quantitative UPLC-Q/TOF-MS method through 3-nitrophenylhydrazine derivatization to investigate the influence of obesity on the gut microbiota in mice. All metabolites could be simultaneously analyzed via separation on a BEH C18 column within 18 min. The lower limits of quantification of most analytes were less than 1 μM. Validation results demonstrated suitability for the analysis of mouse fecal samples. The method was then applied to detect the gut microbiota-derived nutrient metabolome in the feces of high-fat diet induced obese (DIO) and ob/ob (leptin-deficient) mice, as well as obesity-prone (OP) and obesity-resistant (OR) mice. Compared to the control groups, there were 13, 23 and 10 differentially abundant metabolites detected in ob/ob, DIO and OP groups, respectively. Among them, amino acids including leucine, isoleucine, glycine, methionine, tyrosine and glutamine were co-downregulated in the obese or OP mice and exhibited inverse association with body weight. 16S rDNA analysis revealed that the genera Lactobacillus and Dubosiella were also inversely associated with body weight and positively correlated with fecal amino acids. Collectively, our work provides an effective and simplified method for simultaneous quantifying the gut microbiota-derived core nutrient metabolome in mouse feces, which could assist various future studies on host-microbiota metabolic interaction.

肠道微生物群通过产生各种膳食营养素代谢物与宿主相互作用。在此，我们提出了肠道微生物衍生的核心营养代谢组的概念，涵盖了碳水化合物代谢、糖酵解、三羧酸循环和氨基酸代谢中的 43 种代谢物，并通过 3-硝基苯肼建立了定量 UPLC-Q/TOF-MS 方法衍生化研究肥胖对小鼠肠道菌群的影响。所有代谢物都可以在 18 分钟内通过在 BEH C18 色谱柱上的分离同时分析。大多数分析物的定量下限小于 1 μM。验证结果表明适用于小鼠粪便样本的分析。ob/ob（瘦素缺陷）小鼠，以及易肥胖（OP）和抗肥胖（OR）小鼠。与对照组相比，在ob/ob中检测到 13、23 和 10 种差异丰富的代谢物，分别是 DIO 和 OP 组。其中，亮氨酸、异亮氨酸、甘氨酸、蛋氨酸、酪氨酸和谷氨酰胺等氨基酸在肥胖或 OP 小鼠中被共同下调，并与体重呈负相关。16S rDNA 分析表明，乳杆菌属和杜氏杆菌属也与体重呈负相关，与粪便氨基酸呈正相关。总的来说，我们的工作提供了一种有效且简化的方法，可同时量化小鼠粪便中肠道微生物群衍生的核心营养代谢组，这有助于未来对宿主-微生物群代谢相互作用的各种研究。