Maternal gut microbiota reflecting poor diet quality is associated with spontaneous preterm birth in a prospective cohort study

A processed diet, high in fat and low in fiber, is associated with differences in the gut microbiota and adverse health outcomes in humans; however, little is known about the diet–microbiota relation and its impact on pregnancy. Spontaneous preterm birth (SPTB), a pregnancy outcome with serious short- and long-term consequences, occurs more frequently in black and in obese women in the United States. In a prospective, case-control sample matched for race and obesity (cases = 16, controls = 32), we compared the fecal gut microbiota, fecal and plasma metabolites, and diet in the late second trimester. We hypothesized that a Western diet would be associated with reduced microbiota richness and a metabolic signature predicting incidence of SPTB. The fecal microbiota was characterized by 16S-tagged sequencing and untargeted metabolomics was used to analyze both plasma and fecal metabolites. Wilcoxon’s rank-sum test was used for the comparison of microbiota genera, α-diversity, fecal and plasma metabolites, and dietary variables between term and SPTB. β-Diversity was analyzed using permutational multivariate ANOVA, and metabolite associations were assessed by module analysis. A decrease in α-diversity was strongly associated with the development of SPTB, especially in the taxonomic class of Betaproteobacteria. Of 824 fecal metabolites, 22 metabolites (mostly lipids) differed between cases and controls (P < 0.01), with greater DHA (22:6n–3) and EPA (20:5n–3) in cases [false discovery rate (FDR) < 0.2]. The most significant fecal metabolite module (FDR-adjusted P = 0.008) was dominated by DHA and EPA. Dietary saturated fat (primarily palmitate) intake was greater in cases (31.38 ± 7.37 compared with 26.08 ± 8.62 g, P = 0.045) and was positively correlated with fecal DHA and EPA (P < 0.05). Reduced α-diversity of the gut microbiota and higher excretion of omega-3 (n–3) fatty acids in stool may provide a novel biomarker signature predicting SPTB in women with a low-fiber, high-fat diet. Further investigation of these markers in a larger sample is needed for validation.