How far are we from reliable metabolomics-based biomarkers? The often-overlooked importance of addressing inter-individual variability factors.

Metabolomics has proven great potential to unravel the molecular basis of diseases. However, most attempts aimed at identifying reliable metabolomics-based biomarkers for diagnosis, prediction, and prognosis of diseases have repeatedly failed because of inconsistent results and unsatisfactory replication in independent cohorts. This review article explores the possible causes behind this reproducibility crisis, with special focus on the role that inter-individual variability factors play in modulating the susceptibility to disease development. Furthermore, we provide future perspectives on the applicability of metabolomics in biomedical research and its translatability into clinical practice.