National Institute of Immunology, New Delhi, India.
Systems Biology of Aging laboratory, Department of Genetics and Development, Columbia University, New York, NY, USA.
Br J Nutr. 2024 Sep 28;132(6):712-724. doi: 10.1017/S0007114524002022. Epub 2024 Oct 4.
Deficiency of vitamin B (B or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B deficiency lack specificity and sensitivity. Delays in detecting B deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B levels control individuals, we set out to identify biomarker(s) of B insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B levels. Mechanistic studies using a mouse model of B deficiency showed that B deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B deficiency.
维生素 B（B 或钴胺素）缺乏症是一种必需的水溶性维生素缺乏症，可导致神经损伤，这种损伤可能是不可逆转的，并会引起贫血，而且有时还与骨质疏松症和心血管疾病等慢性疾病有关。用于检测 B 缺乏症的临床检测缺乏特异性和敏感性。B 缺乏症的检测延迟会造成严重威胁，因为器官功能的逐渐下降可能在损伤进展或不可逆转之前未被察觉。在这里，我们使用针对低 B 水平个体（对照个体）的血清进行靶向非偏见代谢组学分析，旨在确定 B 不足的生物标志物。代谢组学分析鉴定出了 77 种代谢物，偏最小二乘判别分析和层次聚类分析显示低 B 水平个体中牛磺酸、黄嘌呤、次黄嘌呤、鹅去氧胆酸、新蝶呤和甘氨胆酸的丰度存在差异。随机森林多元分析确定了牛磺酸/鹅去氧胆酸比值，AUC 评分为 1，是预测低 B 水平的最佳生物标志物。使用 B 缺乏症小鼠模型进行的机制研究表明，B 缺乏症重塑了细胞的转录组和代谢组景观，导致蛋氨酸、牛磺酸、尿素循环和核苷酸代谢下调，以及三羧酸循环上调。因此，我们提出血清中的牛磺酸/鹅去氧胆酸比值可作为人类低 B 水平的潜在生物标志物，并使用 B 缺乏症调节的细胞代谢途径的小鼠模型阐明其机制。
