Department of Nutrition, UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28082, USA.
Department of Food Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, 28081, USA.
Sci Rep. 2021 Jan 8;11(1):248. doi: 10.1038/s41598-020-80093-8.
Prenatal alcohol exposure (PAE) causes permanent cognitive disability. The enteric microbiome generates microbial-dependent products (MDPs) that may contribute to disorders including autism, depression, and anxiety; it is unknown whether similar alterations occur in PAE. Using a mouse PAE model, we performed untargeted metabolome analyses upon the maternal-fetal dyad at gestational day 17.5. Hierarchical clustering by principal component analysis and Pearson's correlation of maternal plasma (813 metabolites) both identified MDPs as significant predictors for PAE. The majority were phenolic acids enriched in PAE. Correlational network analyses revealed that alcohol altered plasma MDP-metabolite relationships, and alcohol-exposed maternal plasma was characterized by a subnetwork dominated by phenolic acids. Twenty-nine MDPs were detected in fetal liver and sixteen in fetal brain, where their impact is unknown. Several of these, including 4-ethylphenylsulfate, oxindole, indolepropionate, p-cresol sulfate, catechol sulfate, and salicylate, are implicated in other neurological disorders. We conclude that MDPs constitute a characteristic biosignature that distinguishes PAE. These MDPs are abundant in human plasma, where they influence physiology and disease. Their altered abundance here may reflect alcohol's known effects on microbiota composition and gut permeability. We propose that the maternal microbiome and its MDPs are a previously unrecognized influence upon the pathologies that typify PAE.
产前酒精暴露（PAE）会导致永久性认知障碍。肠道微生物组产生微生物依赖性产物（MDPs），这些产物可能与自闭症、抑郁和焦虑等疾病有关；目前尚不清楚 PAE 是否会发生类似的改变。我们使用一种小鼠 PAE 模型，在妊娠第 17.5 天对母婴对进行了非靶向代谢组学分析。主成分分析的层次聚类和母体血浆的 Pearson 相关性（813 种代谢物）都将 MDPs 鉴定为 PAE 的重要预测因子。其中大多数是富含 PAE 的酚酸。相关网络分析表明，酒精改变了血浆 MDP-代谢物的关系，暴露于酒精的母体血浆的特征是由酚酸主导的子网。在胎肝中检测到 29 种 MDP，在胎脑中检测到 16 种 MDP，其影响尚不清楚。其中一些，包括 4-乙基苯磺酸、吲哚、吲哚丙酸、对甲酚硫酸盐、儿茶素硫酸盐和水杨酸盐，与其他神经紊乱有关。我们得出结论，MDPs 构成了一个独特的生物特征，可以区分 PAE。这些 MDP 在人类血浆中含量丰富，它们影响生理和疾病。它们在这里的丰度改变可能反映了酒精对微生物群落组成和肠道通透性的已知影响。我们提出，母体微生物组及其 MDPs 是以前未被认识到的对 PAE 典型病理的影响因素。
