Bacterial components/virulence factors may be involved in modulating inflammatory responses and include: lipopolysaccharides (LPS), peptidoglycans, lipotechoic acids, fimbriae, proteases, heat-shock proteins, formyl-methionyl peptides, and toxins. Potential host cell receptors involved in recognizing bacterial components and initiating signalling pathways that lead to inflammatory responses include: Toll-like receptors (TLRs), CD14, nucleotide-binding oligomerization domain proteins (Nod) and G-protein-coupled receptors, including formyl-methionyl peptide receptors and protease-activated receptors. Of the above bacterial and host molecules, evidence from experimental animal studies implicate LPS, fimbriae, proteases, TLRs, and CD14 in periodontal tissue or alveolar bone destruction. However, evidence verifying the involvement of any of the above molecules in periodontal tissue destruction in humans does not exist.

Aim: To evaluate the evidence on potential biological pathways underlying the possible association between periodontal disease (PD) and adverse pregnancy outcomes (APOs). Material & Methods: Human, experimental and in vitro studies were evaluated. Results: Periodontal pathogens/byproducts may reach the placenta and spread to the foetal circulation and amniotic fluid. Their presence in the foeto‐placental compartment can stimulate a foetal immune/inflammatory response characterized by the production of IgM antibodies against the pathogens and the secretion of elevated levels of inflammatory mediators, which in turn may cause miscarriage or premature birth. Moreover, infection/inflammation may cause placental structural changes leading to pre‐eclampsia and impaired nutrient transport causing low birthweight. Foetal exposure may also result in tissue damage, increasing the risk for perinatal mortality/morbidity. Finally, the elicited systemic inflammatory response may exacerbate local inflammatory responses at the foeto‐placental unit and further increase the risk for APOs. Conclusions: Further investigation is still necessary to fully translate the findings of basic research into clinical studies and practice. Understanding the systemic virulence potential of the individual's oral microbiome and immune response may be a distinctly different issue from categorizing the nature of the challenge using clinical signs of PD. Therefore, a more personalized targeted therapy could be a more predictive answer to the current “one‐size‐fits‐all” interventions.

Maternal oral infection, caused by bacteria such as C. rectus or P. gingivalis, has been implicated as a potential source of placental and fetal infection and inflammatory challenge, which increases the relative risk for pre-term delivery and growth restriction. Intra-uterine growth restriction has also been reported in various animal models infected with oral organisms. Analyzing placental tissues of infected growth-restricted mice, we found down-regulation of the imprinted Igf2 gene. Epigenetic modification of imprinted genes via changes in DNA methylation plays a critical role in fetal growth and development programming. Here, we assessed whether C. rectus infection mediates changes in the murine placenta Igf2 methylation patterns. We found that infection induced hypermethylation in the promoter region-P0 of the Igf2 gene. This novel finding, correlating infection with epigenetic alterations, provides a mechanism linking environmental signals to placental phenotype, with consequences for development.

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