Placental TLR recognition of salivary and subgingival microbiota is associated with pregnancy complications.

BACKGROUND: Pre-term birth, the leading cause of neonatal mortality, has been associated with maternal periodontal disease and the presence of oral pathogens in the placenta. However, the mechanisms that underpin this link are not known. This investigation aimed to identify the origins of placental microbiota and to interrogate the association between parturition complications and immune recognition of placental microbial motifs. Video Abstract METHODS: Saliva, plaque, serum, and placenta were collected during 130 full-term (FT), pre-term (PT), or pre-term complicated by pre-eclampsia (PTPE) deliveries and subjected to whole-genome shotgun sequencing. Real-time quantitative PCR was used to measure toll-like receptors (TLR) 1-10 expression in placental samples. Source tracking was employed to trace the origins of the placental microbiota. RESULTS: We discovered 10,007 functionally annotated genes representing 420 taxa in the placenta that could not be attributed to contamination. Placental microbial composition was the biggest discriminator of pregnancy complications, outweighing hypertension, BMI, smoking, and maternal age. A machine-learning algorithm trained on this microbial dataset predicted PTPE and PT with error rates of 4.05% and 8.6% (taxonomy) and 6.21% and 7.38% (function). Logistic regression revealed 32% higher odds of parturition complication (95% CI 2.8%, 81%) for every IQR increase in the Shannon diversity index after adjusting for maternal smoking status, maternal age, and gravida. We also discovered distinct expression patterns of TLRs that detect RNA- and DNA-containing antigens in the three groups, with significant upregulation of TLR9, and concomitant downregulation of TLR7 in PTPE and PT groups, and dense correlation networks between microbial genes and these TLRs. 70-82% of placental microbiota were traced to serum and thence to the salivary and subgingival microbiomes. The oral and serum microbiomes of PTPE and PT groups displayed significant enrichment of genes encoding iron transport, exosome, adhesion, quorum sensing, lipopolysaccharide, biofilm, and steroid degradation. CONCLUSIONS: Within the limits of cross-sectional analysis, we find evidence to suggest that oral bacteria might translocate to the placenta via serum and trigger immune signaling pathways capable of inducing placental vascular pathology. This might explain, in part, the higher incidence of obstetric syndromes in women with periodontal disease.

Betwixt and Between: Intracranial Perspective on Zygomatic Arch Plasticity and Function in Mammals.

The zygomatic arch is morphologically complex, providing a key interface between the viscerocranium and neurocranium. It also serves as an attachment site for masticatory muscles, thereby linking it to the feeding apparatus. Though morphological variation related to differential loading is well known for many craniomandibular elements, the adaptive osteogenic response of the zygomatic arch remains to be investigated. Here, experimental data are presented that address the naturalistic influence of masticatory loading on the postweaning development of the zygoma and other cranial elements. Given the similarity of bone-strain levels among the zygoma and maxillomandibular elements, a rabbit and pig model were used to test the hypothesis that variation in cortical bone formation and biomineralization along the zygomatic arch and masticatory structures are linked to increased stresses. It was also hypothesized that neurocranial structures would be minimally affected by varying loads. Rabbits and pigs were raised for 48 weeks and 8 weeks, respectively. In both experimental models, CT analyses indicated that elevated masticatory loading did not induce differences in cortical bone thickness of the zygomatic arch, though biomineralization was positively affected. Hypotheses were supported regarding bone formation for maxillomandibular and neurocranial elements. Varying osteogenic responses in the arch suggests that skeletal adaptation, and corresponding variation in performance, may reside differentially at one level of bony architecture. Thus, it is possible that phenotypic diversity in the mammalian zygoma is due more singularly to natural selection (vs. plasticity). These findings underscore the complexity of the zygomatic arch and, more generally, determinants of skull form. Anat Rec, 299:1646-1660, 2016. © 2016 Wiley Periodicals, Inc.