Alterations in gut microbiota composition, plasma lipids, and brain activity, suggest inter-connected pathways influencing malnutrition-associated cognitive and neurodevelopmental changes.

Abstract Malnutrition affects over 30 million children annually and has profound immediate and enduring repercussions, with nearly half of child deaths under five linked to malnutrition. Survivors face lasting consequences, including impaired neurocognitive development, leading to cognitive and behavioural deficits, impacting academic performance and socioeconomic outcomes. Despite extensive literature on malnutrition’s associations with infections, metabolism, microbiome, and genomics, knowledge gaps persist around how these changes are mechanistically connected. The objective of this study was to identify gut microbiome mediated associations between Moderate Acute Malnutrition (MAM) and cognitive development. Despite limitations, this study provides evidence supporting the hypothesis that inter-connected pathways between the gut microbiome, microbial metabolism mediate plasma lipids, brain activity, and cognitive functions. Causality between gut microbiome, plasma metabolite changes, and MAM phenotype remains unclear, necessitating further research. However, these findings offer insights to optimize interventions for MAM-associated neurodevelopmental changes.