{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:21:07Z","timestamp":1779909667930,"version":"3.53.1"},"posted":{"date-parts":[[2023,8,16]]},"group-title":"Microbiology","reference-count":57,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,16]]},"abstract":"Summary<\/jats:title>\n \n Background<\/jats:title>\n The vaginal microbiome (VMB) has been classified into several discrete community state types, some of which have been associated with adverse human health conditions. However, the roles of the many vaginal bacteria in modulating the VMB and health remain unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The associations among the vaginal taxa and other vaginal taxa, the vaginal pH, and the host gene expression responses were determined by calculating the correlation among the relative abundance of the vaginal taxa, the association between the vaginal pH and the predominant taxon in the VMB, and the correlation between the relative abundance of the vaginal taxa and human gene expression at the transcriptional level, respectively. Using these associations, an alternative more informative method, the biological vagitype (BVT), is proposed to classify community state types of the VMB.<\/jats:p>\n <\/jats:sec>\n \n Findings<\/jats:title>\n \n Most\n Lactobacillus<\/jats:italic>\n spp., with the exception of\n Lactobacillus iners<\/jats:italic>\n , show significant correlations with host gene expression profiles and negative associations with dysbiosis-associated vaginal taxa. Many non-\n Lactobacillus<\/jats:italic>\n spp. exhibit varied correlations with\n Lactobacillus<\/jats:italic>\n spp., the vaginal pH, and host gene expression. Compared to other dysbiotic taxa, including\n Candidatus<\/jats:italic>\n Lachnocurva vaginae,\n Gardnerella vaginalis<\/jats:italic>\n has a stronger positive correlation with vaginal pH and a stronger negative correlation with\n Lactobacillus<\/jats:italic>\n spp. Most dysbiosis-associated taxa are associated with stress responses of the host at the transcriptional level, but the genus\n Mycoplasma<\/jats:italic>\n has a uniquely strong positive correlation with host immune responses. The association between BVTs of the VMBs and host characteristics, e.g., race\/ethnicity, microbial infection, smoking, antibiotics, high blood pressure, economic state, diet, and others, was examined. The BVT classification method improved overall performance in associating specific vaginal microbial populations with host characteristics and phenotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n This study sheds light on the biological characteristics of the vaginal microbiota, including some less abundant or still unculturable taxa. Since the BVT method was established based on these biological characteristics, the classification outcome of the VMB may have more clinical relevance. Because the BVT method performs better in associating specific vaginal community types with diseases, e.g., bacterial vaginosis and gonorrhea, it could be beneficial for the predictive modeling of adverse health.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This work was supported by grants [UH3AI083263, U54HD080784, and R01HD092415] from the National Institutes of Health; and support from the [GAPPS BMGF PPB] grant from the Global Alliance to Prevent Prematurity and Stillbirth. We would also like to thank the Office of Research on Women\u2019s Health at NIH for their generous support.<\/jats:p>\n <\/jats:sec>\n \n Research in context<\/jats:title>\n \n Evidence before this study<\/jats:title>\n \n The vaginal microbiome (VMB) refers to the community of microorganisms in the female lower reproductive tract. The VMB is often a simple ecosystem dominated by a single species. The most predominant bacteria in the VMB include several\n Lactobacillus<\/jats:italic>\n species and two non-\n Lactobacillus<\/jats:italic>\n species, i.e.,\n Candidatus<\/jats:italic>\n Lachnocurva vaginae and\n Gardnerella vaginalis. Lactobacillus<\/jats:italic>\n species produce lactic acid to lower the vaginal pH and inhibit the growth of disease-associated bacteria. Thus, the predominance of protective Lactobacilli, i.e.,\n L. crispatus, L. jensenii<\/jats:italic>\n , and\n L. gasseri<\/jats:italic>\n , in the VMB is associated with overall vaginal health. However, the role of\n L. iners<\/jats:italic>\n in promoting a healthy vaginal ecosystem is less clear. Actually, the biological and health relevance of many bacteria in the female lower reproductive tract is largely unknown. Some bacteria have low relative abundances, e.g.,\n Peptostreptococcus<\/jats:italic>\n and\n Coriobacteriaceae<\/jats:italic>\n spp.; and others are not yet culturable, e.g.,\n Candidatus<\/jats:italic>\n Lachnocurva vaginae and BVAB TM7. When abundance of a taxon is low, its association with a host characteristic is a challenge. Previous methods to classify the VMB were based simply on their microbial compositions, and the biological characteristics of the vaginal bacteria were largely ignored. Thus, classification of these VMBs into biologically relevant community types, as described herein, should be helpful in determining their relevance to women\u2019s reproductive health.\n <\/jats:p>\n <\/jats:sec>\n \n Added value of this study<\/jats:title>\n \n This study examines three biological characteristics of bacteria in the VMB, i.e., the associations among different bacterial taxa, the vaginal pH, and the host response. Based on these three characteristics, the influence of these bacteria, particularly low abundant and unculturable bacteria, on vaginal health is evaluated.\n L. iners<\/jats:italic>\n seems to be neutral in maintaining overall vaginal health.\n Gardnerella vaginalis<\/jats:italic>\n is apparently more easily inhibited by\n Lactobacillus<\/jats:italic>\n spp. than\n Candidatus<\/jats:italic>\n Lachnocurva vaginae because of its stronger positive correlation with vaginal pH and negative correlation with\n Lactobacillus<\/jats:italic>\n . The genus of\n Mycoplasma<\/jats:italic>\n has a unique positive correlation with local immune responses, implying a role for\n Mycoplasma<\/jats:italic>\n in promoting inflammation. Compared with previous methods to classify the VMB, a new method, considering the above three biological characteristics of bacteria in the VMB, has been established. The new method performs better in associating specific vaginal communities with host characteristics and phenotypes; e.g., bacterial vaginosis and gonorrhea.\n <\/jats:p>\n <\/jats:sec>\n \n Implications of all the available evidence<\/jats:title>\n Accurate biological classification of the VMB is fundamental for assessing its impact on women\u2019s health. Our classification scheme represents a step further toward that correct classification, eventually leading to new strategies for clinical assessment of the potential use of the VMB to diagnose or predict women\u2019s reproductive health.<\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1101\/2023.08.16.553525","type":"posted-content","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T01:20:12Z","timestamp":1692235212000},"source":"Crossref","is-referenced-by-count":2,"title":["Characteristics of vaginal microbes and classification of the vaginal microbiome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2829-2925","authenticated-orcid":false,"given":"Bin","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M.","family":"Spaine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laahirie","family":"Edupuganti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Matveyev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4327-0193","authenticated-orcid":false,"given":"Myrna G.","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-3987","authenticated-orcid":false,"given":"Gregory A.","family":"Buck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023082107500989000_2023.08.16.553525v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11234"},{"key":"2023082107500989000_2023.08.16.553525v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0465-8"},{"key":"2023082107500989000_2023.08.16.553525v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002611107"},{"key":"2023082107500989000_2023.08.16.553525v1.4","doi-asserted-by":"crossref","unstructured":"VALENCIA: a nearest centroid classification method for vaginal microbial communities based on composition. vol. 8 (2020).","DOI":"10.1186\/s40168-020-00934-6"},{"key":"2023082107500989000_2023.08.16.553525v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.11.1089"},{"key":"2023082107500989000_2023.08.16.553525v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.01.013"},{"key":"2023082107500989000_2023.08.16.553525v1.7","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00181-21"},{"key":"2023082107500989000_2023.08.16.553525v1.8","doi-asserted-by":"crossref","first-page":"792787","DOI":"10.3389\/fcimb.2021.792787","article-title":"Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review","volume":"11","year":"2021","journal-title":"Front. 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