Abstract：
Prenatal stress (PNS) profoundly impacts maternal and offspring health, with enduring effects including microbiome alterations, neuroinflammation, and behavioral disturbances such as reductions in social behavior. Converging lines of evidence from preclinical and clinical studies suggest that PNS disrupts tryptophan (Trp) metabolic pathways and reduces gut Bifidobacteria, a known beneficial bacterial genus that metabolizes Trp. Specifically, previous work from our lab demonstrated that human prenatal mood disorders in mothers are associated with reduced Bifidobacterium dentium in infants at 13 months. Given that Bifidobacterium has been positively associated with neurodevelopmental and other health benefits and is depleted by PNS, we hypothesized that supplementing PNS-exposed pregnant dams with B. dentium would ameliorate PNS-induced health deficits. We measured inflammatory outputs, Trp metabolite levels and enzymatic gene expression in dams and fetal offspring, and social behavior in adult offspring. We determined that B. dentium reduced maternal systemic inflammation and fetal offspring neuroinflammation, while modulating tryptophan metabolism and increasing kynurenic acid and indole-3-propionic acid intergenerationally. Additional health benefits were demonstrated by the abrogation of PNS-induced reductions in litter weight. Finally, offspring of the B. dentium cohort demonstrated increased sociability in males primarily and increased social novelty primarily in females. Together these data illustrate that B. dentium can orchestrate interrelated host immune, metabolic and behavioral outcomes during and after gestation for both dam and offspring and may be a candidate for prevention of the negative sequelae of stress.
摘要：
产前压力（PNS）深刻影响孕产妇和后代的健康，具有持久的影响，包括微生物组的改变，神经炎症，和行为障碍，如社会行为的减少。临床前和临床研究的证据表明，PNS破坏色氨酸（Trp）代谢途径并减少肠道双歧杆菌，一种已知的代谢Trp的有益细菌属。具体来说,我们实验室先前的研究表明,母亲的人类产前情绪障碍与13个月时婴儿的双歧杆菌减少相关.鉴于双歧杆菌与神经发育和其他健康益处呈正相关，并且被PNS耗尽，我们假设在暴露于PNS的孕鼠中补充牙菌根杆菌可以改善PNS引起的健康缺陷.我们测量了炎症输出，大坝和胎儿后代的Trp代谢物水平和酶基因表达，和成年后代的社会行为。我们确定B.dentium减少母体全身性炎症和胎儿后代神经炎症，同时调节色氨酸代谢并代际增加犬尿烯酸和吲哚-3-丙酸。通过废除PNS诱导的产仔数减少，证明了其他健康益处。最后,B.dentium队列的后代主要表现出男性的社交能力增强，主要表现出女性的社会新颖性增强。这些数据共同说明了B.denterum可以协调相关的宿主免疫，大坝和后代在妊娠期间和妊娠后的代谢和行为结果，可能是预防压力负面后遗症的候选者。
