Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy

Abstract

Background: Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women. Methods: Physically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26 weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22–34 weeks gestation; plasma interleukin-6 (IL-6), interleukin-1β (IL-1β), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated. Results: Forty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (q=5.7×10^−13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-α and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (p=0.03) and eicosapentaenoic acid (EPA) (p=0.05). Discussion: Our findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of ω-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.

Effects of a Diet Supplemented with Exogenous Catalase from Penicillium notatum on Intestinal Development and Microbiota in Weaned Piglets

“…Moreover, the abundance of Bifidobacterium was positive to antioxidative capacity [62]. Members of the Dialister genus are asaccharolytic obligately anaerobic gram-negative coccobacilli, and negatively associated with pro-inflammatory cytokine response [63,64]. Streptococcus and Escherichia-Shigella are both pathogenic bacteria.…”

Glucocorticoid receptor sensitivity in early pregnancy in an African American cohort

“…Going forward, prospective data in African American women with healthy versus adverse outcomes would inform our understanding of the potential role of immune dysregulation in racial disparities in birth outcomes among women at high risk for chronic stress and immune activation. Additionally, investigation into the role of early life experiences 56 and coping mechanisms developed over the life course 53 may offer insight into protective factors.…”

Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development

“…These observations in humans are reflected in experimental animal models of early-life stress, which have long been used to model both psychological and gastrointestinal disorders (O'Mahony et al, 2011). Moreover, a number of recent studies have demonstrated links between prenatal stress (including maternal anxiety) or early-life adversity (i.e., postnatal stress) and alterations in the human microbiota across the life span (Callaghan et al, in press;D'Agata et al, 2019;Hantsoo et al, 2019;Hemmings et al, 2017;Hu et al, 2019;Labus et al, 2017;Michels et al, 2019;Zijlmans et al, 2015).…”