Maternal gut microbiota disruption alters postpartum maternal behavior in association with modulation of stress responses and brain tryptophan metabolism in mice.

The maternal gut microbiota serves as a primary source of microbial transmission to offspring and plays a critical role in offspring development; however, its contribution to maternal mental states during the perinatal period remains poorly understood. In this study, we investigated how perturbation of maternal gut microbiota during pregnancy affects postpartum behavior using a mouse model treated with non-absorbable antibiotics. Antibiotic-treated dams exhibited increased offspring mortality and altered maternal behavior during the postpartum period. These behavioral alterations were accompanied by elevated plasma corticosterone and IL-6 levels, indicating enhanced stress and inflammatory responses. Plasma metabolomic and amino acid profiles in antibiotic-treated dams did not align with those typically observed in depression models or patients diagnosed with depressive disorders. Furthermore, tryptophan metabolism tended to shift towards the kynurenine pathway in key brain regions of antibiotic-treated dams. Together, these findings suggest that maternal gut microbiota contributes to the regulation of postpartum maternal behavior, which is associated with modulation of stress responses and brain tryptophan metabolism. This study highlights a previously underappreciated role of the maternal microbiota in maintaining maternal mental well-being and suggests potential targets for preventing maladaptive maternal behaviors that affect offspring development.