{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:18:51Z","timestamp":1785853131567,"version":"3.56.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Research Chairs Initiative of the National Research Foundation","award":["64815"],"award-info":[{"award-number":["64815"]}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001325","name":"Cancer Association of South Africa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001325","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Cape Town (UCT) Research Incentive Scheme"},{"name":"University of Cape Town Cancer Research Initiative"},{"name":"University of Cape Town International and Refugee Students\u2019 Scholarship"},{"name":"University of Cape Town Faculty of Health Sciences Postdoctoral Research Fellowship"},{"name":"South African Research Chairs Initiative of the National Research Foundation (NRF) Postdoctoral Grantholder Bursary"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Mounting evidence suggests that <jats:italic>Lactobacillus<\/jats:italic> species may not necessarily be the <jats:italic>sine qua non<\/jats:italic> of healthy cervicovaginal microbiota (CVM), especially among reproductive-age African women. A majority of African women have high-diversity non-<jats:italic>Lactobacillus<\/jats:italic>-dominated CVM whose bacterial functions remain poorly characterized. Functional profiling of the CVM is vital for investigating human host-microbiota interactions in health and disease. Here, we investigated the functional potential of <jats:italic>L<\/jats:italic>. <jats:italic>iners<\/jats:italic>-dominated and high-diversity non-<jats:italic>Lactobacillus<\/jats:italic>-dominated CVM of 75 African women with and without bacterial vaginosis (BV) and high-risk human papillomavirus (HR-HPV) infection. Functional contents were predicted using PICRUSt. Microbial taxonomic diversity, BV, and HR-HPV infection statuses were correlated with the inferred functional composition of the CVM. Differentially abundant inferred functional categories were identified using linear discriminant analysis (LDA) effect size (LEfSe) (p-value &lt;0.05 and logarithmic LDA score &gt;2.0). Of the 75 women, 56 (74.7%), 35 (46.7%), and 29 (38.7%) had high-diversity non-<jats:italic>Lactobacillus<\/jats:italic>-dominated CVM, BV, and HR-HPV infection, respectively. Alpha diversity of the inferred functional contents (as measured by Shannon diversity index) was significantly higher in women with high-diversity non-<jats:italic>Lactobacillus<\/jats:italic>-dominated CVM and BV than their respective counterparts (H statistic \u226511.5, q-value &lt;0.001). Ordination of the predicted functional metagenome content (using Bray-Curtis distances) showed that the samples segregated according to the extent of microbial taxonomic diversity and BV (pseudo-F statistic \u226519.6, q-value = 0.001) but not HR-HPV status (pseudo-F statistic = 1.7, q-value = 0.159). LEfSe analysis of the inferred functional categories revealed that transport systems (including ABC transporters) and transcription factors were enriched in high-diversity CVM. Interestingly, transcription factors and sporulation functional categories were uniquely associated with high-diversity CVM, BV, and HR-HPV infection. Our predictive functional analysis reveals features unique to high-diversity CVM, BV and HR-HPV infections. Such features may represent important biomarkers of BV and HR-HPV infection. Our findings require proof-of-concept functional studies to examine the relevance of these potential biomarkers in women\u2019s reproductive health and disease.<\/jats:p>","DOI":"10.1371\/journal.pone.0253218","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T17:25:13Z","timestamp":1624037113000},"page":"e0253218","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Predictive functional analysis reveals inferred features unique to cervicovaginal microbiota of African women with bacterial vaginosis and high-risk human papillomavirus infection"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7298-4921","authenticated-orcid":true,"given":"Harris","family":"Onywera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Anejo-Okopi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-1787","authenticated-orcid":true,"given":"Lamech M.","family":"Mwapagha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-5448","authenticated-orcid":true,"given":"Javan","family":"Okendo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-1200","authenticated-orcid":true,"given":"Anna-Lise","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"pone.0253218.ref001","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3389\/fphys.2015.00081","article-title":"Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health","volume":"6","author":"MI Petrova","year":"2015","journal-title":"Front Physiol"},{"issue":"Pt 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