Maternal dysbiosis produces long-lasting behavioral changes in offspring

Advanced maternal age (AMA) is defined as pregnancy in a woman older than 35 years and is linked to adverse maternal and neonatal outcomes and to neurodevelopmental and neuropsychiatric disorders in offspring. Aging alters gut microbiota composition, metabolism, and inflammation. To isolate the effect of the maternal microbiome on pregnancy outcomes and offspring behavior, young female mice were recolonized prior to pregnancy with microbiota from aged female donors. Pre-pregnancy colonization of young dams with aged microbiome increased fetal loss. Offspring born to dams recolonized with aged female microbiota exhibited gut microbiome compositional differences that persisted into middle age, along with altered blood and brain neurotransmitters and metabolites. Adult offspring demonstrated persistent depressive- and anxiety-like phenotypes. These results indicate that age-related changes in maternal gut microbiome composition contribute to chronic alterations in offspring behavior and physiology, suggesting microbiome-targeted approaches before birth may reduce neuropsychiatric risk.