Paula T Littlejohn, Ravi Holani, Bruce A Vallance, B Brett Finlay
Malnutrition poses a substantial global health burden with long-lasting physical, social and economic effects. Now recognized as an spectrum of interrelated conditions, malnutrition manifests differently based on an individual's geography, health-care access and lifestyle. There is growing evidence that malnutrition is also driven by defects in the composition and function of the gut microbiota, a metabolically active 'virtual organ' known to play a central role in intestinal barrier function, energy harvest, immune regulation and metabolic signalling. Across the malnutrition spectrum, perturbed microbial composition and function have been consistently observed in both children and adults. This 'malnourished microbiota' is associated with impaired nutrient utilization, chronic inflammation and altered energy balance and is known to persist despite nutritional interventions. This Review synthesizes evidence from human cohorts and animal models showing that the gut microbiota functions as a central player in malnutrition. We discuss implications for diagnostic and therapeutic strategies, arguing that microbiome restoration could provide a partial solution for malnutrition. This reframing is particularly relevant given current challenges such as armed conflict, climate change and declining international support, all of which are associated with an increased global burden of malnutrition. Thus, integrating microbiota-based strategies could protect vulnerable populations and accelerate progress towards overcoming malnutrition.