Immunomodulatory Potential of Vaginal Microbiota-Derived Metabolites in Pregnant Women: Insights from ADMET Profiling and Molecular Docking

Background: Pregnancy involves coordinated immunological adaptations that maintain maternal–fetal tolerance while preserving protection against infections. There is growing evidence that vaginal microbiota-associated metabolites contribute to immune balance, yet their molecular mechanisms remain incompletely understood. Methods: This study used an in silico approach combining absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling, molecular docking, and structural interaction analysis. Eight compounds—five organic acids, two bacteriocins, and hydrogen peroxide—were evaluated against eight immune and inflammatory protein targets relevant to pregnancy. Results: The ADMET predictions revealed favorable pharmacokinetic and safety profiles for small organic acids, particularly butyric and propionic acids. Enterocin-HF yielded the most favorable predicted binding energies across the evaluated targets, particularly TNF-α and NF-κB. Redocking of the COX-2 co-crystallized ligand reproduced the experimental binding pose with an RMSD of 1.21 Å, supporting the ability of the protocol to recover the crystallographic binding mode. Conclusions: Overall, these findings prioritize Enterocin-HF and selected organic acids for subsequent experimental evaluation. However, the predicted interactions should not be interpreted as evidence of functional immunomodulation or therapeutic efficacy.