Maternal dysbiosis produces long-lasting behavioral changes in offspring

Abstract

Advanced maternal age (AMA) is defined as a pregnancy in a woman older than 35 years of age. AMA increases the risk for both maternal and neonatal complications, including miscarriage and stillbirth. AMA has also been linked to neurodevelopmental and neuropsychiatric disorders in the offspring. Recent studies have found that age-associated compositional shifts in the gut microbiota contribute to altered microbial metabolism and enhanced inflammation in the host. We investigated the specific contribution of the maternal microbiome on pregnancy outcomes and offspring behavior by recolonizing young female mice with aged female microbiome prior to pregnancy. We discovered that pre-pregnancy colonization of young dams with microbiome from aged female donors significantly increased fetal loss. There were significant differences in the composition of the gut microbiome in pups born from dams recolonized with aged female biome that persisted through middle age. Offspring born from dams colonized with aged microbiome also had significant changes in levels of neurotransmitters and metabolites in the blood and the brain. Adult offspring from dams colonized with an aged microbiome displayed persistent depressive- and anxiety-like phenotypes. Collectively, these results demonstrate that age-related changes in the composition of the maternal gut microbiome contribute to chronic alterations in the behavior and physiology of offspring. This work highlights the potential of microbiome-targeted approaches, even prior to birth, may reduce the risk of neuropsychiatric disorders.