Rajasekera Therese A, Galley Jeffrey D, Mackos Amy R, Chen Helen J, Mitchell Justin G, Kleinman Joshua J, Cappelucci Paige, Mashburn-Warren Lauren, Lauber Christian L, Bailey Michael T, Worly Brett L, Gur Tamar L
Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Brain Behav Immun Health. 2024 Jan 26;36:100730. doi: 10.1016/j.bbih.2024.100730. eCollection 2024 Mar.
Psychosocial stress and mood-related disorders, such as depression, are prevalent and vulnerability to these conditions is heightened during pregnancy. Psychosocial stress induces consequences via several mechanisms including the gut microbiota-brain axis and associated signaling pathways. Previous preclinical work indicates that prenatal stress alters maternal gut microbial composition and impairs offspring development. Importantly, although the fecal and vaginal microenvironments undergo alterations across pregnancy, we lack consensus regarding which shifts are adaptive or maladaptive in the presence of prenatal stress and depression. Clinical studies interrogating these relationships have identified unique taxa but have been limited in study design.
We conducted a prospective cohort study of pregnant individuals consisting of repeated administration of psychometrics (Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES-D)) and collection of fecal and vaginal microbiome samples. Fecal and vaginal microbial community composition across psychometric responses were interrogated using full-length 16S rRNA sequencing followed by α and β-diversity metrics and taxonomic abundance.
Early pregnancy stress was associated with increased abundance of fecal taxa not previously identified in related studies, and stress from late pregnancy through postpartum was associated with increased abundance of typical vaginal taxa and opportunistic pathogens in the fecal microenvironment. Additionally, in late pregnancy, maternal stress and depression scores were associated with each other and with elevated maternal C-C motif chemokine ligand 2 (CCL2) concentrations. At delivery, concordant with previous literature, umbilical CCL2 concentration was negatively correlated with relative abundance of maternal fecal Lastly, participants with more severe depressive symptoms experienced steeper decreases in prenatal vaginal α-diversity.
These findings a) underscore previous preclinical and clinical research demonstrating the effects of prenatal stress on maternal microbiome composition, b) suggest distinct biological pathways for the consequences of stress versus depression and c) extend the literature by identifying several taxa which may serve critical roles in mediating this relationship. Thus, further interrogation of the role of specific maternal microbial taxa in relation to psychosocial stress and its sequelae is warranted.
心理社会压力和与情绪相关的疾病，如抑郁症，很常见，而且在孕期对这些疾病的易感性会增加。心理社会压力通过多种机制产生影响，包括肠道微生物群-脑轴及相关信号通路。先前的临床前研究表明，产前压力会改变母体肠道微生物组成并损害后代发育。重要的是，尽管整个孕期粪便和阴道微环境都会发生变化，但对于产前压力和抑郁症情况下哪些变化是适应性的或适应不良的，我们尚未达成共识。研究这些关系的临床研究已经确定了独特的分类群，但在研究设计方面存在局限性。
我们对孕妇进行了一项前瞻性队列研究，包括重复进行心理测量（感知压力量表（PSS）和流行病学研究中心抑郁量表（CES-D））以及收集粪便和阴道微生物组样本。使用全长16S rRNA测序，随后进行α和β多样性指标及分类丰度分析，探究心理测量反应中的粪便和阴道微生物群落组成。
孕早期压力与相关研究中未发现的粪便分类群丰度增加有关，而孕晚期至产后的压力与粪便微环境中典型阴道分类群和机会性病原体的丰度增加有关。此外，在孕晚期，母体压力和抑郁评分相互关联，且与母体C-C基序趋化因子配体2（CCL2）浓度升高有关。分娩时，与先前文献一致，脐带CCL2浓度与母体粪便相对丰度呈负相关。最后，抑郁症状更严重的参与者产前阴道α多样性下降更明显。
这些发现a）强调了先前的临床前和临床研究，证明了产前压力对母体微生物组组成的影响，b）表明压力与抑郁后果的不同生物学途径，c）通过识别几个可能在介导这种关系中起关键作用的分类群扩展了文献。因此，有必要进一步探究特定母体微生物分类群在心理社会压力及其后遗症方面的作用。
