Histidine metabolism is a key pathway physiologically involved in satiety, recognition memory, skin, and neural protection and allergic diseases. Microbiologically-produced imidazole propionate induces type II diabetes and interferes with glucose lowering drugs. Despite their determinant health implications, no single method simultaneously assesses histidine metabolites in urine, feces, and microbiota. The aim of this study was to develop a simple, rapid, and sensitive method for the determination of histidine and its major bioactive metabolites histamine, N-acetylhistamine, imidazole-4-acetate, cis-urocanate, trans-urocanate, glutamate and imidazole propionate, using ultrahigh-performance liquid chromatography with electrospray ionization tandem mass spectrometry. An innovative simple extraction method from small aliquots of human and mice urine, feces and microbial cell extracts was coupled to separation in a 6.5 min chromatographic run. The successful performance allowed accurate and precise quantification of all metabolites in mouse feces, suggesting broad exchange of histidine metabolites between the gut and mice. Higher urine histamine, histamine to histidine ratio, and imidazole-4-acetate pointed to an underlying inflammatory or allergic process in mice compared to human subjects. N-acetylhistamine and imidazole propionate were detected in human and mouse feces, confirming its origin from gut microbial metabolism. Our novel and robust analytical method captured histidine metabolism in a single assay that will facilitate broad and deep histidine metabolic phenotyping assessing the impact of microbiota on host health in large-scale human observational and interventional studies.

中文翻译：

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快速同时测定人和小鼠微生物群和生物基质中的组氨酸代谢中间体

组氨酸代谢是生理上与饱腹感、识别记忆、皮肤、神经保护和过敏性疾病有关的关键途径。微生物产生的丙酸咪唑可诱发 II 型糖尿病并干扰降糖药物。尽管它们具有决定性的健康影响，但没有一种方法可以同时评估尿液、粪便和微生物群中的组氨酸代谢物。本研究的目的是开发一种简单、快速、灵敏的方法来测定组氨酸及其主要生物活性代谢物组胺、N-乙酰组胺、咪唑-4-乙酸酯、顺式尿康酸酯、反式-尿康酸、谷氨酸和丙酸咪唑，采用超高效液相色谱法和电喷雾电离串联质谱法。从人和小鼠尿液、粪便和微生物细胞提取物的小等分试样中提取一种创新的简单提取方法，在 6.5 分钟的色谱运行中进行分离。成功的表现允许对小鼠粪便中的所有代谢物进行准确和精确的量化，表明肠道和小鼠之间存在广泛的组氨酸代谢物交换。与人类受试者相比，较高的尿液组胺、组胺与组氨酸比率和 4-乙酸咪唑表明小鼠存在潜在的炎症或过敏过程。在人和小鼠的粪便中检测到 N-乙酰组胺和丙酸咪唑，证实其起源于肠道微生物代谢。