Taurine/chenodeoxycholic acid ratio as a circulating biomarker of insidious vitamin B12 deficiency in humans

Deficiency of vitamin B12 (B12), an essential water-soluble vitamin, leads to irreversible neurological damage, osteoporosis, cardiovascular diseases, and anemia. Clinical tests to detect B12deficiency lack specificity and sensitivity. B12 deficiency is thus insidious because 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 B12-deficient versus control individuals, we set out to identify biomarker(s) of B12 deficiency. Metabolomic profiling identified 77 metabolites, and Partial least squares discriminant-analysis (PLS-DA) and hierarchical clustering analysis (HCA) showed a differential abundance in B12-deficient sera of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin, and glycocholic acid. Random forest (RF) multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict B12 deficiency. Mechanistically, B12 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 B12 deficiency in humans and elucidate cellular metabolic pathways regulated by B12 deficiency.