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.

高龄产妇 （AMA） 定义为 35 岁以上女性怀孕。AMA 会增加孕产妇和新生儿并发症的风险，包括流产和死产。AMA 还与后代的神经发育和神经精神疾病有关。最近的研究发现，肠道微生物群中与年龄相关的组成变化会导致宿主的微生物代谢改变和炎症增强。我们通过在怀孕前用老年雌性微生物组重新定植年轻雌性小鼠来研究母体微生物组对妊娠结局和后代行为的具体贡献。我们发现，来自老年女性供体的微生物组在年轻母体的孕前定植显着增加了胎儿丢失。在持续到中年的老年雌性生物群落重新定植的大坝所生的幼崽中，肠道微生物组的组成存在显着差异。从定植有衰老微生物组的母细胞中出生的后代在血液和大脑中的神经递质和代谢物水平也有显着变化。来自用衰老微生物组定植的母体的成年后代表现出持续的抑郁和焦虑样表型。总的来说，这些结果表明，母体肠道微生物组组成的年龄相关变化会导致后代行为和生理的慢性改变。这项工作强调了微生物组靶向方法的潜力，甚至在出生前，就可以降低神经精神疾病的风险。