Translating metabolomic evidence gathered from an animal model to a real human scenario: the post-mortem interval issue

Introduction Translating findings from animal models to human applications remains a fundamental challenge across scientific research, with unique implications for post-mortem metabolomics. Objectives This work is aimed at applying NMR metabolomics to human aqueous humour for post-mortem interval estimation, based on a previously studied ovine model. Methods Quantitative metabolomic profiling of 21 aqueous humour samples collected during from 11 forensic autopsies, with post-mortem intervals between 225 and 1164 min has been performed by H-1 NMR spectroscopy. Results Most of the identified metabolites in human aqueous humour samples are shared with those previously identified in ovine samples, showing qualitative similarities, while quantitative differences in metabolites such as lactate and glutamate are observed due to species-specific factors. Partial least squares regression models for post-mortem interval estimation resulted less accurate in human model with respect to the ovine one underscoring translational complexity. Of note, taurine and hypoxanthine were identified as post-mortem interval-specific metabolites independently on the species, suggesting their relevance in the post-mortem. Conclusions This study is the first attempt to translate animal to human post-mortem metabolomics using a rigorous methodology. Direct translation to humans seems possible for a limited part of the metabolome, with key metabolites such as taurine and hypoxanthine showing some consistency. These findings support animal model metabolomics as a guide for human studies across diverse metabolomics investigations, promoting human studies on larger cohorts and more specific experimental designs.