The Molecular and Histopathological Landscape of Ascending Bacterial Infection in Obstetrics: From Vaginal Dysbiosis to Fetal Inflammatory Response Syndrome and Precision Perinatal Interventions

Spontaneous preterm birth and preterm premature rupture of membranes (pPROM) remain the primary challenges in perinatal medicine. Traditional approaches frequently underestimate the microenvironmental shifts within the intrauterine cavity. This review synthesizes four decades of research from the Hospital Clínico San Borja-Arriarán (HCSBA) group, establishing a comprehensive pathophysiological model of Ascending Bacterial Infection (ABI) in preterm birth between 24 and 34 weeks of gestation. We detail the sequential transition from vaginal dysbiosis—characterized by the loss of protective Lactobacillus species and the emergence of high-risk community state types (CST III/IV)—to cellular invasion. Key molecular virulence factors of prominent pathogens (Streptococcus agalactiae, non-typeable Haemophilus influenzae, and extended-spectrum beta-lactamase-producing Escherichia coli) are evaluated, highlighting their mechanisms to evade host innate immunity, disrupt the cervical mucosal barrier, and trigger intrauterine inflammation via the TLR4/NF-κB and TNF-α signaling pathways. Furthermore, we examine the clinical implications of biological compartmentalization and synergistic systemic triggers, such as periodontal disease. Finally, we analyze how transitioning from reactive, symptom-based protocols toward precision perinatology—utilizing ultra-rapid quantitative PCR (qPCR) and histopathological evaluation (CORM method)—can optimize targeted antimicrobial and immunomodulatory interventions before irreversible fetal injury occurs.