(948) Longitudinal assessment of prothrombotic and proatherogenic gut microbial metabolites in pregnancy

To evaluate trends in maternal serum levels of pro-thrombotic/atherogenic and cardioprotective gut microbial metabolites and their precursors across pregnancy in a prospective cohort.

Study Design:
Prospective cohort study enrolling patients ≥ 18 years with singleton pregnancy between 10-14 weeks’ gestation. Maternal blood was collected at 10-14 weeks (visit 1), 24-28 weeks (visit 2), and at time of delivery (visit 3). Assays for predetermined gut microbial metabolites, phenylacetylglutamine (PAG), indole acetic acid (IAA), trimethylamine-N-oxide (TMAO), and indole-3-propionic acid (I3PA), and their nutrient precursors were performed using isotope dilution LC-MS/MS methods. Results were summarized and compared across visits.

Results:
Concentrations for each metabolite across visits are displayed in Figure 1. PAG and IAA increased across gestation, I3PA decreased, and TMAO remained stable. Dietary precursors for TMAO: choline, betaine, g-butyrobetaine, crotonobetaine, carnitine, and trimethyl-lysine all increased from visit 1 to visit 3. Phenylalanine, precursor for PAG, transiently increased at visit 2 but was similar between visit 1 and 3. Tryptophan, precursor for IAA and I3PA, also increased from visit 1 to visit 3 (table 1).

Conclusion:
These gut microbial metabolites demonstrated distinct trajectories across pregnancy. Pro-thrombotic/atherogenic metabolite PAG increased over time, while cardioprotective I3PA decreased. IAA, with likely cardioprotective mechanisms, increased. Despite rising levels of TMAO precursors, TMAO itself remained stable, indicating regulation beyond substrate availability. These findings highlight dynamic changes in gut-derived metabolites throughout gestation and underscore the interaction of diet, microbial activity, and host metabolism. Longitudinal shifts in these metabolites may have implications for maternal cardiometabolic health and warrant further investigation.