Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study

Trichomonas vaginalis is a flagellated protozoan affecting human reproductive health. Although bacterial coinfections have been associated with T. vaginalis infection outcomes, pertinent data are scarce. This study was aimed at assessing vaginal bacterial community changes regarding T. vaginalis out...

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Autores:
Camargo, Milena
Vega, Laura
Muñoz, Marina
Ramírez, Juan David
Patarroyo, Manuel-Alfonso
Pedraza, Lady
Báez Murica, Indira M.
Tipo de recurso:
Article of investigation
Fecha de publicación:
2025
Institución:
Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
Repositorio:
Repositorio Institucional UDCA
Idioma:
eng
OAI Identifier:
oai:repository.udca.edu.co:11158/6325
Acceso en línea:
https://repository.udca.edu.co/handle/11158/6325
https://doi.org/10.1007/s00436-025-08482-4
https://repository.udca.edu.co/
Palabra clave:
610 - Medicina y salud
Microbiota
Epidemiología
Trichomonas vaginalis
Estudios de Seguimiento
Rights
openAccess
License
https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.es
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repository_id_str
dc.title.eng.fl_str_mv Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
title Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
spellingShingle Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
610 - Medicina y salud
Microbiota
Epidemiología
Trichomonas vaginalis
Estudios de Seguimiento
title_short Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
title_full Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
title_fullStr Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
title_full_unstemmed Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
title_sort Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study
dc.creator.fl_str_mv Camargo, Milena
Vega, Laura
Muñoz, Marina
Ramírez, Juan David
Patarroyo, Manuel-Alfonso
Pedraza, Lady
Báez Murica, Indira M.
dc.contributor.author.none.fl_str_mv Camargo, Milena
Vega, Laura
Muñoz, Marina
Ramírez, Juan David
Patarroyo, Manuel-Alfonso
Pedraza, Lady
Báez Murica, Indira M.
dc.subject.ddc.none.fl_str_mv 610 - Medicina y salud
topic 610 - Medicina y salud
Microbiota
Epidemiología
Trichomonas vaginalis
Estudios de Seguimiento
dc.subject.armarc.none.fl_str_mv Microbiota
Epidemiología
dc.subject.decs.none.fl_str_mv Trichomonas vaginalis
Estudios de Seguimiento
description Trichomonas vaginalis is a flagellated protozoan affecting human reproductive health. Although bacterial coinfections have been associated with T. vaginalis infection outcomes, pertinent data are scarce. This study was aimed at assessing vaginal bacterial community changes regarding T. vaginalis outcomes (infection, clearance, persistence) during patients’ follow-up visits. This was a 1-year follow-up study involving Colombian women who provided two cytological scrapings from the cervix (one at baseline and another at follow-up), having an average 12 ± 1 month follow-up interval. T. vaginalis was detected by conventional PCR (Tvk3/7 and BTU9/2 primers). The Illumina Novaseq PE250-platform was used for assessing microbiota composition. This study involved 66 women (132 samples); 68.2% (n = 45) tested negative for T. vaginalis at baseline while 31.8% (n = 21) were initially diagnosed with T. vaginalis infection (99,304 amplicon sequence variants identified/categorised into 62 phyla and 1908 genera). Women who cleared T. vaginalis (n = 10) displayed increased microbial richness, while those having persistence (n = 11) had higher microbial diversity. Significant changes were observed regarding genus relative abundance: Lactobacillus abundance increased in the clearance group (p = 0.002), Prevotella in the persistence group (p = 0.045) and Gardnerella, Megasphaera and Sneathia in the group having acquired T. vaginalis infection (p = 0.045). Regarding relative abundance, logistic regression analysis revealed a positive trend concerning Sneathia increase (adjusted OR 2.23) and reduced Lactobacillus abundance (adjusted OR 0.39) in women with T. vaginalis persistence. DESeq analysis revealed a substantial decrease in the Ornithinimicrobium genus among women without infection during follow-up, while Ruminococcus increased in women having various T. vaginalis outcomes. The results suggested that specific bacterial genera present during T. vaginalis infection may influence its clearance, having potential implications for improving diagnostic and therapeutic strategies for enhancing women’s reproductive health.
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-05-21T16:38:10Z
dc.date.available.none.fl_str_mv 2025-05-21T16:38:10Z
dc.date.issued.none.fl_str_mv 2025
dc.type.none.fl_str_mv Artículo de revista
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dc.identifier.citation.none.fl_str_mv Camargo, M., Vega, L., Muñoz, M., Hernández-Buelvas, L., Pedraza, L., Báez-Murcia, I. M., Ramírez, J. D., & Patarroyo, M. A. (2025). Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study. Parasitology Research, 124(3), 37. https://doi.org/10.1007/s00436-025-08482-4
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identifier_str_mv Camargo, M., Vega, L., Muñoz, M., Hernández-Buelvas, L., Pedraza, L., Báez-Murcia, I. M., Ramírez, J. D., & Patarroyo, M. A. (2025). Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study. Parasitology Research, 124(3), 37. https://doi.org/10.1007/s00436-025-08482-4
09320113
Universidad de Ciencias Aplicadas y Ambientales
UDCA
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https://doi.org/10.1007/s00436-025-08482-4
https://repository.udca.edu.co/
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.indexed.none.fl_str_mv LaReferencia
dc.relation.citationedition.none.fl_str_mv (Mar., 2025) Artículo número 37
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dc.relation.citationvolume.none.fl_str_mv 124
dc.relation.ispartofjournal.none.fl_str_mv Parasitology Research
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spelling Camargo, Milenavirtual::604-1Vega, LauraMuñoz, Marinavirtual::605-1Ramírez, Juan Davidvirtual::608-1Patarroyo, Manuel-Alfonsovirtual::609-1Pedraza, LadyBáez Murica, Indira M.2025-05-21T16:38:10Z2025-05-21T16:38:10Z2025Camargo, M., Vega, L., Muñoz, M., Hernández-Buelvas, L., Pedraza, L., Báez-Murcia, I. M., Ramírez, J. D., & Patarroyo, M. A. (2025). Unveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal study. Parasitology Research, 124(3), 37. https://doi.org/10.1007/s00436-025-08482-4https://repository.udca.edu.co/handle/11158/6325https://doi.org/10.1007/s00436-025-08482-409320113Universidad de Ciencias Aplicadas y AmbientalesUDCAhttps://repository.udca.edu.co/Trichomonas vaginalis is a flagellated protozoan affecting human reproductive health. Although bacterial coinfections have been associated with T. vaginalis infection outcomes, pertinent data are scarce. This study was aimed at assessing vaginal bacterial community changes regarding T. vaginalis outcomes (infection, clearance, persistence) during patients’ follow-up visits. This was a 1-year follow-up study involving Colombian women who provided two cytological scrapings from the cervix (one at baseline and another at follow-up), having an average 12 ± 1 month follow-up interval. T. vaginalis was detected by conventional PCR (Tvk3/7 and BTU9/2 primers). The Illumina Novaseq PE250-platform was used for assessing microbiota composition. This study involved 66 women (132 samples); 68.2% (n = 45) tested negative for T. vaginalis at baseline while 31.8% (n = 21) were initially diagnosed with T. vaginalis infection (99,304 amplicon sequence variants identified/categorised into 62 phyla and 1908 genera). Women who cleared T. vaginalis (n = 10) displayed increased microbial richness, while those having persistence (n = 11) had higher microbial diversity. Significant changes were observed regarding genus relative abundance: Lactobacillus abundance increased in the clearance group (p = 0.002), Prevotella in the persistence group (p = 0.045) and Gardnerella, Megasphaera and Sneathia in the group having acquired T. vaginalis infection (p = 0.045). Regarding relative abundance, logistic regression analysis revealed a positive trend concerning Sneathia increase (adjusted OR 2.23) and reduced Lactobacillus abundance (adjusted OR 0.39) in women with T. vaginalis persistence. DESeq analysis revealed a substantial decrease in the Ornithinimicrobium genus among women without infection during follow-up, while Ruminococcus increased in women having various T. vaginalis outcomes. The results suggested that specific bacterial genera present during T. vaginalis infection may influence its clearance, having potential implications for improving diagnostic and therapeutic strategies for enhancing women’s reproductive health.Incluye referencias bibliográficasapplication/pdfenghttps://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.eshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2https://link.springer.com/article/10.1007/s00436-025-08482-4?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=scopus610 - Medicina y saludMicrobiotaEpidemiologíaTrichomonas vaginalisEstudios de SeguimientoUnveiling shifts in cervical microbiota composition among Colombian women in the presence of Trichomonas vaginalis: a longitudinal studyArtículo de 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jecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.</li>
      <li>
        Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
        <ol type="i">
          <li>Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.</li>
          <li>Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
        </ol>
      </li>
      <li>Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
    </ol>
  </li>
  <br/>
  <li>
    Representaciones, Garantías y Limitaciones de Responsabilidad.
    <p>A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Limitación de responsabilidad.
    <p>A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Término.
    <ol type="a">
      <li>Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.</li>
      <li>Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.</li>
    </ol>
  </li>
  <br/>
  <li>
    Varios.
    <ol type="a">
      <li>Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.</li>
      <li>Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.</li>
      <li>Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.</li>
      <li>Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.</li>
    </ol>
  </li>
  <br/>
</ol>
