Metabolomics of Acute Malnutrition Recovery in Nigerian Children: Identifying Biomarkers of Metabolic Restoration and Predicting Treatment Response

Severe acute malnutrition (SAM) is associated with profound metabolic derangements that current anthropometric recovery criteria fail to fully capture, resulting in children being discharged as recovered while carrying persistent metabolic vulnerabilities. Metabolomic profiling offers the potential to characterise metabolic recovery trajectories and identify biomarkers predictive of treatment response and relapse risk. This translational study employs untargeted plasma metabolomics using liquid chromatography-mass spectrometry (LC-MS) to profile metabolic signatures in children aged 6 to 36 months at admission, mid-treatment, and discharge from the SAM treatment programme at Aminu Kano Teaching Hospital, Kano State, North West Nigeria. A total of 120 SAM children and 60 well-nourished community controls were enrolled. Multivariate statistical analysis using principal component analysis and partial least squares-discriminant analysis identified metabolite clusters distinguishing SAM from recovery states. At admission, SAM was characterised by profound depletion in branched-chain amino acids, phosphatidylcholines, and carnitine species, with simultaneous elevation of organic acid intermediates reflecting mitochondrial dysfunction. Children achieving anthropometric recovery showed only partial metabolic restoration, with persistent carnitine and tryptophan depletion at discharge. Metabolic recovery completeness at discharge was a significant predictor of six-month relapse (AUC 0.83). A 12-metabolite panel distinguished complete from incomplete metabolic recovery with 81.7% accuracy. This study generates the first Nigerian paediatric SAM metabolomics dataset, providing an original contribution to the biological understanding of malnutrition recovery and identifying candidate biomarkers for improved discharge criteria. Keywords: metabolomics, severe acute malnutrition, biomarkers, treatment response, Kano State.