Riboflavin and the pediatric gut–brain axis: Interplay between diet and microbiota with emerging probiotic applications

The microbiota-gut-brain axis (MGBA) is a complex bidirectional communication system that plays a critical role in neurodevelopment, particularly during pediatric development, when the gut microbiota and the central nervous system undergo rapid and coordinated maturation. Dysbiosis due to external or physiological conditions may predispose to long-term neurological consequences. While microbiota-targeted interventions are gaining interest, the mechanistic role of specific microbial metabolites is often overlooked. This review highlights the role of riboflavin (vitamin B2) within the framework of pediatric MGBA. As an essential cofactor in mitochondrial energy metabolism, redox homeostasis, and neurotransmitter synthesis, riboflavin represents a vital intersection between nutrition and host-microbe interactions. Dietary intake remains the primary determinant of riboflavin status. However, changes in dietary habits and physiological conditions may lead to deficiencies influencing local availability and host-microbe interactions. Furthermore, riboflavin-overproducing probiotics are discussed as an emerging, function-driven strategy to modulate the MGBA. By enabling in situ vitamin production, these strains offer a targeted approach to enhance local bioavailability and promote beneficial microbial cross-feeding. Finally, we address current limitations in the field, emphasizing the lack of specific biomarkers to quantify host-accessible microbial riboflavin and the critical need for standardized pediatric clinical trials to translate experimental findings into evidence-based therapies.