Association of Gastrointestinal Microbial Profiles and Estrogen Metabolism in Patients With Preterm Birth [21A]

INTRODUCTION: Researchers have explored various causes for preterm birth (PTB); yet, the effects of maternal gastrointestinal microbiome on estrogen metabolism and its influence on pregnancy remains unknown. The aim of this study is to analyze the effects of maternal gastrointestinal microbiome on estrogen metabolism during pregnancy by correlating the estrogen metabolite bioactivity with preterm birth. METHODS: Study participants (IRB#14-185) were recruited at Southern Illinois University School of Medicine, Department of Ob/Gyn. Twenty-four patients identified as being at risk for a repeat, PTB were recruited. Biological samples (urine and fecal samples) were collected during each trimester and a postpartum timepoint. Fecal samples were frozen and processed for DNA isolation. Microbial analyses were performed by miSeq amplicon sequencing using the V4 region of the bacterial 16S rRNA gene. Identification of 15 estrogen metabolites (2-, 4- and 16-hydroxylation pathways) in urine samples was performed using tandem mass spectrophotometry analysis. Data was evaluated using analysis of variance (ANOVA) and then by repeat measure design. RESULTS: Of the 24 patients, 18 delivered at term and 6 delivered preterm (25%). Gastrointestinal microbial profiles were altered in women with subsequent PTB. Additionally, decreased urinary levels of estrone, 17-epiestriol and 17-estradiol were found as early as the first trimester in subjects who delivered prematurely. CONCLUSION: This study highlights the interaction of the gastrointestinal microbiome on estrogen metabolism, possibly through hormone conjugation. Unbalanced levels of estrogen during pregnancy may predispose women to PTB. This investigation may elucidate novel screening tools to identify patients at risk for PTB and enable early clinical intervention.