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^].

Ethical approval

Not applicable, as the manuscript does not involve original data collection or identifiable patient information.

Consent

Not applicable.

Sources of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

Conceptualization, literature review, and drafting of the manuscript: H.P.; data interpretation, literature search, and manuscript writing: D.M.P.; literature review, critical revision, and editing of the manuscript: M.M.; supervision, writing – original manuscripts, final review, guarantor of the work, and approval of the manuscript for submission: A.K.M. All authors contributed to the manuscript and approved the final version.

Conflicts of interest disclosure

None.

Research Registration Unique Identifying Number (UIN)

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Guarantor

Amrendra kumar Mahato.

Provenance and peer review

Not applicable.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

AI usage

During the preparation of this work, the authors used ChatGPT and Grammarly to rectify grammar and spelling mistakes, check reference suitability, and tighten language. After using these tools, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Declaration

We confirm that this submission complies with the TITAN 2025 guidelines, and the completed checklist is attached.

Acknowledgements

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