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In this study, we conducted a metapangenomic analysis of oral\n                      <jats:italic>Haemophilus<\/jats:italic>\n                      and\n                      <jats:italic>Aggregatibacter<\/jats:italic>\n                      species to uncover genomic diversity, phylogenetic relationships, and habitat specialization within the human oral cavity. Using three metrics\u2014pangenomic gene content, phylogenomics, and average nucleotide identity (ANI)\u2014we first identified distinct species and sub-species groups among these genera. Mapping of metagenomic reads then revealed clear patterns of habitat specialization, such as\n                      <jats:italic>Aggregatibacter<\/jats:italic>\n                      species predominantly in dental plaque, a distinctive\n                      <jats:italic>Haemophilus parainfluenzae<\/jats:italic>\n                      sub-species group on the tongue dorsum, and\n                      <jats:italic>H<\/jats:italic>\n                      . sp. HMT-036 predominantly in keratinized gingiva and buccal mucosa. In addition, we found that supragingival plaque samples contained predominantly only one out of the three taxa,\n                      <jats:italic>H. parainfluenzae<\/jats:italic>\n                      ,\n                      <jats:italic>Aggregatibacter aphrophilus<\/jats:italic>\n                      , and\n                      <jats:italic>A<\/jats:italic>\n                      . sp. HMT-458, suggesting independent niches or a competitive relationship. Functional analyses revealed the presence of key metabolic genes, such as oxaloacetate decarboxylase, correlated with habitat specialization, suggesting metabolic versatility as a driving force. Additionally, heme synthesis distinguishes\n                      <jats:italic>H<\/jats:italic>\n                      . sp. HMT-036 from closely related\n                      <jats:italic>Haemophilus haemolyticus<\/jats:italic>\n                      , suggesting that the availability of micronutrients, particularly iron, was important in the evolutionary ecology of these species. Overall, our study exemplifies the power of metapangenomics to identify factors that may affect ecological interactions within microbial communities, including genomic diversity, habitat specialization, and metabolic versatility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Understanding the microbial ecology of the mouth is essential for comprehending human physiology. This study employs metapangenomics to reveal that various\n                      <jats:italic>Haemophilus<\/jats:italic>\n                      and\n                      <jats:italic>Aggregatibacter<\/jats:italic>\n                      species exhibit distinct ecological preferences within the oral cavity of healthy individuals, thereby supporting the site-specialist hypothesis. Additionally, it was observed that the gene pool of different\n                      <jats:italic>Haemophilus<\/jats:italic>\n                      species correlates with their ecological niches. These findings shed light on the significance of key metabolic functions in shaping microbial distribution patterns and interspecies interactions in the oral ecosystem.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.04017-23","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T08:41:16Z","timestamp":1710492076000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Spatial ecology of\n                    <i>Haemophilus and Aggregatibacter<\/i>\n                    in the human oral cavity"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-894X","authenticated-orcid":true,"given":"Jonathan J.","family":"Giacomini","sequence":"first","affiliation":[{"name":"The Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Torres-Morales","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Tang","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4427-7928","authenticated-orcid":true,"given":"Floyd E.","family":"Dewhirst","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Cambridge, Massachusetts, USA"},{"name":"Harvard School of Dental Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary G.","family":"Borisy","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Mark Welch","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Cambridge, Massachusetts, USA"},{"name":"Marine Biological Laboratory, Woods Hole, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11234"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-016-0307-y"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177486"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.04042-22"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12387"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2023.2225261"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090817-062503"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409644111"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02200-2"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00103-13"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319284111"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00653-07"},{"key":"e_1_3_4_14_2","first-page":"97","article-title":"STUDIES ON BACTERIALNUTRITION: II. growth accessory substances in the cultivation of Hemophilic Bacilli","volume":"34","author":"Thj\u00f6tta T","year":"1921","unstructured":"Thj\u00f6tta T, Avery OT. 1921. 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