{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:39:44Z","timestamp":1787593184343,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Understanding the intricate relationship between sex, age, and the oral microbiome is crucial for deciphering the onset and progression of numerous age\u2010related oral and systemic diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Subgingival plaque was collected from 781 periodontally and systemically healthy females and 160 males spanning 0 to 80 years. 16S amplicon sequencing was performed. 80 million sequences were annotated and analyzed through the QIIME pipeline, principal components analysis (PCA) used for dimensionality reduction, LefSe to identify driver species, beta dispersion to measure inter\u2010subject variability, and machine learning algorithm (\n                      <jats:italic>RandomForest<\/jats:italic>\n                      package in R [RF]) to validate the results. Causal mediation models were implemented to investigate the influence of aging on the male and female microbiomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PCA demonstrated significant class separation based on sex (\n                      <jats:italic>p\u00a0&lt;<\/jats:italic>\n                      \u00a00.001, permutational multivariate analysis of variance [PERMANOVA]). Males demonstrated higher alpha diversity (\n                      <jats:italic>p\u00a0&lt;<\/jats:italic>\n                      \u00a00.001, Wilcoxon signed\u2010rank test of the Shannon diversity index), but also higher inter\u2010subject heterogeneity\n                      <jats:italic>p\u00a0&lt;<\/jats:italic>\n                      \u00a00.001, ANOVA). RF identified males with 0.99 sensitivity, 0.15 specificity, and accuracy of 85%. Age exerted an almost complete mediation effect, with significant differences in the trajectory and pattern of aging between males and females. Females\u00a0&gt;\u00a030 demonstrated a lower microbial diversity (\n                      <jats:italic>p\u00a0&lt;<\/jats:italic>\n                      \u00a00.001) and higher levels of\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      (\n                      <jats:italic>p\u00a0&lt;<\/jats:italic>\n                      \u00a00.001), while the male microbiome remained highly personalized throughout the lifespan, without defined patterns of aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sex and age interact to influence the subgingival microbiome. These findings might explain differing disease susceptibilities in either sex, as well as informing personalized prevention and intervention based on age and sex. Further studies using granular \u2010omics approaches are needed to advance our knowledge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>Periodontal (gum) diseases are caused by a breakdown in the intricate balance between bacteria that live under the gumline and the local immune response. Since periodontal diseases have been reported to be more common in men than in women, we set out to investigate whether these bacterial communities are intrinsically different between the 2 sexes, and whether these differences are sustained over the lifespan. Using deep\u2010sequencing technology to analyze the microbiomes of 941 individuals, we discovered that sex at birth is indeed a determining factor in the types of bacteria that live under the gums. Aging trajectories and patterns also differ between men and women, with women demonstrating a distinct shift after 30 years of age, and men showing no definite age\u2010based change. These findings have important implications for the cause of periodontitis in either sex, as well as the potential to personalize therapy based on age and sex.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70098","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:38:34Z","timestamp":1774255114000},"page":"1659-1671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mapping the subgingival HerBiome and HisBiome over the human healthspan"],"prefix":"10.1002","volume":"97","author":[{"given":"Rahul","family":"Nikam","sequence":"first","affiliation":[{"name":"Department of Periodontics and Oral Medicine School of Dentistry University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazune","family":"Pax","sequence":"additional","affiliation":[{"name":"Division of Oral Biology College of Dentistry The Ohio State University  Columbus Ohio USA"},{"name":"West Chester Center for Dentistry  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Lee\u2010Scott","family":"Beverly","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine School of Dentistry University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purnima S.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine School of Dentistry University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514552491"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12782"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2013.09.010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272427"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12568"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035337\u20108"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fdmed.2024.1430193"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784\u2010025\u201006205\u20108"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512457373"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/idj.12399"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201088249\u20100"},{"issue":"4","key":"e_1_2_8_13_1","first-page":"268","article-title":"Subgingival microbiota associated with puberty: studies of pre\u2010, circum\u2010, and postpubertal human females","volume":"8","author":"Delaney JE","year":"1986","journal-title":"Pediatr Dent"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1990.tb01054.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1980.tb00265.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100757.2011.00398.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17124394"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.11.27.625678"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002533"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915\u2010024\u201002025\u20106"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm21242"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.171311"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010018\u20100443\u20102"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020956"},{"key":"e_1_2_8_26_1","unstructured":"Sickle: A sliding\u2010window adaptive quality\u2010based trimming tool for FastQ files (Version 1.33) [Software]. 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