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Additionally, to investigate if these differences are depicted in immunologic markers in blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Twenty\u2010nine teeth with primary or secondary AP were extracted and cryo\u2010pulverized. Blood was drawn from the subjects at three different time\u2010points before and three time\u2010points after the extraction in a time period of four months. The V4 hypervariable region of the 16S rRNA gene was sequenced using Illumina MiSeq. The microbial profiles were ordinated using principal component analysis and tested for differences between groups with permutational multivariate analysis of variance using the Bray\u2013Curtis distance. If significantly different, the microbial profiles were further analysed using the LDA effect size (LEfSe) biomarker discovery tool. A broad panel of inflammatory mediators in blood was examined longitudinally in all subjects during the six visits with mixed models. The Spearman correlation between these mediators and the zOTUs was calculated, and significant correlations (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05) were used as input for significant analysis of microarrays (SAM) using MeV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After subsampling, the 467 zOTUs were classified into 9 phyla and 99 genera or higher level taxa. The predominant genus in the entire sample set was <jats:italic>Fusobacterium<\/jats:italic> with a relative abundance of 12.3%, followed by <jats:italic>Prevotella<\/jats:italic> (9.9%), <jats:italic>Actinomyces<\/jats:italic> (7.7%) and <jats:italic>Streptococcus<\/jats:italic> (6.7%). The microbiomes of the endodontic infections were significantly associated with endodontic status (primary\/secondary infection; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.015) as well as with the presence or absence of pain (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.011). There was also a difference in the concentration of inflammatory mediators, namely, C\u2010reactive protein, Interleukin (IL)\u20108, IL\u201010, IL\u201012p70, RANKL and TNF\u2010\u03b1, depending on the existence of pain. In addition, the presence of specific bacteria (zOTUs) was correlated, positively or negatively, with the expression of several circulating inflammatory markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The microbial profiles and the concentration\u2013time relationship of systemic inflammatory mediators of primary endodontic infection differed from those of secondary, and of symptomatic from those of asymptomatic cases. The fingerprint of associations between the immunological and microbiological profiles differed between asymptomatic and symptomatic patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13912","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T08:23:37Z","timestamp":1678782217000},"page":"748-764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Host\u2013microbiome interactions in apical periodontitis: The endodontic microbiome in relation to circulatory immunologic markers"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7198-5909","authenticated-orcid":false,"given":"Athina C.","family":"Georgiou","sequence":"first","affiliation":[{"name":"Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-3714","authenticated-orcid":false,"given":"Suzette V.","family":"van der Waal","sequence":"additional","affiliation":[{"name":"Endodontology, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-4104","authenticated-orcid":false,"given":"Mark J.","family":"Buijs","sequence":"additional","affiliation":[{"name":"Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Crielaard","sequence":"additional","affiliation":[{"name":"Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1432-6194","authenticated-orcid":false,"given":"Egija","family":"Zaura","sequence":"additional","affiliation":[{"name":"Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1155-1989","authenticated-orcid":false,"given":"Bernd W.","family":"Brandt","sequence":"additional","affiliation":[{"name":"Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02374"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2013.08.025"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000080107"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211035775"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baq013"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1758-2229.2010.00183.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-019-0049-y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356869"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-7622-8-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2019.07.017"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2020.100686"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2013.05.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13640"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-302X.2003.00078.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034519889015"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(65)90166-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2017.03.019"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2009.41.5.033"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01043-13"},{"key":"e_1_2_10_21_1","unstructured":"Lahti L.&Shetty S.(2021)Tools for microbiome analysis in R. 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