Stress and depression-associated shifts in gut microbiota: A pilot study of human pregnancy

Abstract

Background: 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.

Methods: 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.

Results: 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 Lactobacilli. Lastly, participants with more severe depressive symptoms experienced steeper decreases in prenatal vaginal α-diversity.

Conclusion: 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.

Keywords: Gut microbiome; Maternal microbiome; Perceived stress; Peripartum stress; Pregnancy.

Fig. 1

Study Design. A total of 40 participants enrolled in the prospective cohort study. At each time point, psychometrics were administered and biospecimens were collected, in addition to dietary surveys and information abstracted from medical records (B). The psychometrics assessed global perceived stress and depressive symptoms: Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES-D). The current sample (n = 35) consists of participants who completed both psychometrics and biospecimen collection during at least one study visit which passed quality filtering after sequencing. Several participants were lost throughout the study (Fig. S1).

Fig. 2

Steeper decreases in vaginal α-diversity from early to late pregnancy among participants reporting more severe depressive symptoms, as measured by Shannon’s Entropy (A) (p = 0.009) and Pielou’s Evenness (B) (p = 0.017). Red indicates ‘high’ or more severe depressive symptoms (CES-D score ≥16); blue indicates ‘low’ or less severe depressive symptoms (CES-D score <16). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)