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

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dc.authoridAlan, Murat/0000-0002-9108-2990
dc.authoridPax, Kazune/0000-0002-7651-349X
dc.authoridDabdoub, Shareef/0000-0002-1374-8347
dc.contributor.authorPax, Kazune
dc.contributor.authorBuduneli, Nurcan
dc.contributor.authorAlan, Murat
dc.contributor.authorMeric, Pinar
dc.contributor.authorGurlek, Onder
dc.contributor.authorDabdoub, Shareef M.
dc.contributor.authorKumar, Purnima S.
dc.date.accessioned2024-08-31T07:50:10Z
dc.date.available2024-08-31T07:50:10Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractBackground 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. 61FbVQciH1C2BbwKYgvy28 Video AbstractBackground 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. 61FbVQciH1C2BbwKYgvy28 Video AbstractMethods 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.en_US
dc.description.sponsorshipNational Institute of Dental and Craniofacial Researchen_US
dc.description.sponsorshipNot applicable.en_US
dc.identifier.doi10.1186/s40168-024-01761-9
dc.identifier.issn2049-2618
dc.identifier.issue1en_US
dc.identifier.pmid38532461en_US
dc.identifier.scopus2-s2.0-85188571826en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1186/s40168-024-01761-9
dc.identifier.urihttps://hdl.handle.net/11454/105120
dc.identifier.volume12en_US
dc.identifier.wosWOS:001191282800001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherBmcen_US
dc.relation.ispartofMicrobiomeen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240831_Uen_US
dc.subjectPregnancy Outcomesen_US
dc.subjectPre-Term Birthen_US
dc.subjectPre-Eclampsiaen_US
dc.subjectSalivary Bacteriaen_US
dc.subjectPlacentaen_US
dc.subjectSerumen_US
dc.subjectSubgingivalen_US
dc.subjectDna Sequence Analysisen_US
dc.subjectOral Microbiomeen_US
dc.subjectMetagenomicsen_US
dc.titlePlacental TLR recognition of salivary and subgingival microbiota is associated with pregnancy complicationsen_US
dc.typeArticleen_US

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