Hudobenko Jacob, Di Gesù Claudia M, Mooz Patrick R, Petrosino Joseph, Putluri Nagireddy, Ganesh Bhanu P, Rebeles Kristen, Blixt Frank W, Venna Venugopal R, McCullough Louise D
Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA.
Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, USA.
Mol Psychiatry. 2025 May;30(5):1847-1858. doi: 10.1038/s41380-024-02794-0. Epub 2024 Oct 23.
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.
高龄孕产妇（AMA）定义为年龄超过35岁的女性怀孕。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微生物代谢改变和宿主炎症增强。我们通过在怀孕前用老年雌性小鼠的微生物群对年轻雌性小鼠进行重新定殖，研究了母体微生物群对妊娠结局和后代行为的具体影响。我们发现，用老年雌性供体的微生物群对年轻母鼠进行怀孕前定殖会显著增加胎儿丢失率。用老年雌性生物群落重新定殖的母鼠所生幼崽的肠道微生物群组成存在显著差异，这种差异一直持续到中年。用老年微生物群定殖的母鼠所生后代的血液和大脑中的神经递质和代谢物水平也有显著变化。用老年微生物群定殖的母鼠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，母体肠道微生物群组成的年龄相关变化会导致后代行为和生理的慢性改变。这项工作突出了即使在出生前以微生物群为靶点的方法可能降低神经精神疾病风险的潜力。
