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Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix

Bacterial vaginosis (BV) is an enigmatic polymicrobial condition characterized by a depletion of health-associated Lactobacillus and an overgrowth of anaerobes. Importantly, BV is linked to adverse gynecologic and obstetric outcomes: an increased risk of sexually transmitted infections, preterm birt...

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Autores principales: Łaniewski, Paweł, Herbst-Kralovetz, Melissa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669023/
https://www.ncbi.nlm.nih.gov/pubmed/34903740
http://dx.doi.org/10.1038/s41522-021-00259-8
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author Łaniewski, Paweł
Herbst-Kralovetz, Melissa M.
author_facet Łaniewski, Paweł
Herbst-Kralovetz, Melissa M.
author_sort Łaniewski, Paweł
collection PubMed
description Bacterial vaginosis (BV) is an enigmatic polymicrobial condition characterized by a depletion of health-associated Lactobacillus and an overgrowth of anaerobes. Importantly, BV is linked to adverse gynecologic and obstetric outcomes: an increased risk of sexually transmitted infections, preterm birth, and cancer. We hypothesized that members of the cervicovaginal microbiota distinctly contribute to immunometabolic changes in the human cervix, leading to these sequelae. Our 3D epithelial cell model that recapitulates the human cervical epithelium was infected with clinical isolates of cervicovaginal bacteria, alone or as a polymicrobial community. We used Lactobacillus crispatus as a representative health-associated commensal and four common BV-associated species: Gardnerella vaginalis, Prevotella bivia, Atopobium vaginae, and Sneathia amnii. The immunometabolic profiles of these microenvironments were analyzed using multiplex immunoassays and untargeted global metabolomics. A. vaginae and S. amnii exhibited the highest proinflammatory potential through induction of cytokines, iNOS, and oxidative stress-associated compounds. G. vaginalis, P. bivia, and S. amnii distinctly altered physicochemical barrier-related proteins and metabolites (mucins, sialic acid, polyamines), whereas L. crispatus produced an antimicrobial compound, phenyllactic acid. Alterations to the immunometabolic landscape correlate with symptoms and hallmarks of BV and connected BV with adverse women’s health outcomes. Overall, this study demonstrated that 3D cervical epithelial cell colonized with cervicovaginal microbiota faithfully reproduce the immunometabolic microenvironment previously observed in clinical studies and can successfully be used as a robust tool to evaluate host responses to commensal and pathogenic bacteria in the female reproductive tract.
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spelling pubmed-86690232021-12-28 Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix Łaniewski, Paweł Herbst-Kralovetz, Melissa M. NPJ Biofilms Microbiomes Article Bacterial vaginosis (BV) is an enigmatic polymicrobial condition characterized by a depletion of health-associated Lactobacillus and an overgrowth of anaerobes. Importantly, BV is linked to adverse gynecologic and obstetric outcomes: an increased risk of sexually transmitted infections, preterm birth, and cancer. We hypothesized that members of the cervicovaginal microbiota distinctly contribute to immunometabolic changes in the human cervix, leading to these sequelae. Our 3D epithelial cell model that recapitulates the human cervical epithelium was infected with clinical isolates of cervicovaginal bacteria, alone or as a polymicrobial community. We used Lactobacillus crispatus as a representative health-associated commensal and four common BV-associated species: Gardnerella vaginalis, Prevotella bivia, Atopobium vaginae, and Sneathia amnii. The immunometabolic profiles of these microenvironments were analyzed using multiplex immunoassays and untargeted global metabolomics. A. vaginae and S. amnii exhibited the highest proinflammatory potential through induction of cytokines, iNOS, and oxidative stress-associated compounds. G. vaginalis, P. bivia, and S. amnii distinctly altered physicochemical barrier-related proteins and metabolites (mucins, sialic acid, polyamines), whereas L. crispatus produced an antimicrobial compound, phenyllactic acid. Alterations to the immunometabolic landscape correlate with symptoms and hallmarks of BV and connected BV with adverse women’s health outcomes. Overall, this study demonstrated that 3D cervical epithelial cell colonized with cervicovaginal microbiota faithfully reproduce the immunometabolic microenvironment previously observed in clinical studies and can successfully be used as a robust tool to evaluate host responses to commensal and pathogenic bacteria in the female reproductive tract. Nature Publishing Group UK 2021-12-13 /pmc/articles/PMC8669023/ /pubmed/34903740 http://dx.doi.org/10.1038/s41522-021-00259-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Łaniewski, Paweł
Herbst-Kralovetz, Melissa M.
Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix
title Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix
title_full Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix
title_fullStr Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix
title_full_unstemmed Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix
title_short Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix
title_sort bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3d model of human cervix
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669023/
https://www.ncbi.nlm.nih.gov/pubmed/34903740
http://dx.doi.org/10.1038/s41522-021-00259-8
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