Maternal Tryptophan Supplementation Alters Offspring Gut-Brain Axis and Behavior in a Sex-Specific Manner

The maternal diet is a key determinant of offspring neurodevelopment, influencing gut microbiota composition and the gut-brain axis. These interactions are critical in shaping sex-specific vulnerabilities to neuropsychiatric disorders. Tryptophan, an essential amino acid and precursor to serotonin, plays a pivotal role in neurodevelopment and immune function. However, the impact of maternal tryptophan supplementation on healthy offspring's neurochemical and behavioral outcomes remains unclear. This study investigated the effects of a tryptophan-enriched maternal diet on offspring gut microbiota, metabolism, neurochemical pathways, and behavior. We analyzed microbial composition, metabolic activity, brain, and plasma levels of tryptophan and serotonin, and behavioral outcomes in male and female mice offspring. Maternal tryptophan supplementation led to sex-specific changes. Female offspring exhibited disrupted microbiota diversity, reduced brain tryptophan and serotonin levels, and heightened anxiety-like behaviors. In contrast, male offspring displayed increased metabolic activity, elevated brain tryptophan levels, and repetitive behaviors. These findings suggest that maternal tryptophan supplementation influences offspring neurodevelopment and behavior by modulating gut-brain axis components in a sex-dependent manner. This work underscores the importance of further research into prenatal dietary interventions targeting gut microbiota and neurochemical pathways to support healthy neurodevelopment and potentially inform sex-specific preventive strategies. These findings contribute to a growing understanding of how maternal nutrition influences offspring neurodevelopment and may guide the development of preventive strategies to improve long-term mental health outcomes..