Microbiome-derived metabolites as novel placental functional markers: predictive role in vasa previa

Vasa previa (VP) is a serious pregnancy complication in which fetal vessels, unprotected by Wharton’s jelly, run across or in proximity to the internal cervical os, which can potentially result in fetal exsanguination in the event of membrane rupture[1]. Microbiome-derived metabolites have been implicated in other pregnancy complications characterized by placental dysfunction, highlighting their potential utility as noninvasive markers of placental health[2]. Alterations in maternal metabolite profiles have been shown to influence trophoblast function, inflammation, and vascular signaling pathways critical to placental development[3]. Metabolites from the microbiome are increasingly recognized as important regulators of immune responses and placental vascular development. Short-chain fatty acids, especially butyrate, support angiogenic signaling, maintain endothelial integrity, and help regulate inflammation at the maternal–fetal interface[4]. Changes in the maternal microbiome can alter metabolite levels, potentially disrupting normal placental vessel development and vascular integrity. These alterations may be associated with abnormal placental vascular development and unusual vascular configurations, including VP. Studies linking inflammatory imbalance and impaired angiogenesis to placental vascular abnormalities provide biological plausibility[5]. However, a direct association between microbiome-derived metabolites and VP has not yet been established. Further prospective research is needed to evaluate the predictive value of these metabolites as noninvasive indicators of placental function in VP. This manuscript complies with TITAN Guidelines, 2025, declaring no use of AI[6].