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The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia

BACKGROUND: Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims...

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Autores principales: Mitra, Anita, MacIntyre, David A., Paraskevaidi, Maria, Moscicki, Anna-Barbara, Mahajan, Vishakha, Smith, Ann, Lee, Yun S., Lyons, Deirdre, Paraskevaidis, Evangelos, Marchesi, Julian R., Bennett, Phillip R., Kyrgiou, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567681/
https://www.ncbi.nlm.nih.gov/pubmed/34736529
http://dx.doi.org/10.1186/s13073-021-00977-w
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author Mitra, Anita
MacIntyre, David A.
Paraskevaidi, Maria
Moscicki, Anna-Barbara
Mahajan, Vishakha
Smith, Ann
Lee, Yun S.
Lyons, Deirdre
Paraskevaidis, Evangelos
Marchesi, Julian R.
Bennett, Phillip R.
Kyrgiou, Maria
author_facet Mitra, Anita
MacIntyre, David A.
Paraskevaidi, Maria
Moscicki, Anna-Barbara
Mahajan, Vishakha
Smith, Ann
Lee, Yun S.
Lyons, Deirdre
Paraskevaidis, Evangelos
Marchesi, Julian R.
Bennett, Phillip R.
Kyrgiou, Maria
author_sort Mitra, Anita
collection PubMed
description BACKGROUND: Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. METHODS: We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. RESULTS: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment. CONCLUSIONS: Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-021-00977-w.
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spelling pubmed-85676812021-11-04 The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia Mitra, Anita MacIntyre, David A. Paraskevaidi, Maria Moscicki, Anna-Barbara Mahajan, Vishakha Smith, Ann Lee, Yun S. Lyons, Deirdre Paraskevaidis, Evangelos Marchesi, Julian R. Bennett, Phillip R. Kyrgiou, Maria Genome Med Research BACKGROUND: Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. METHODS: We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. RESULTS: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment. CONCLUSIONS: Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-021-00977-w. BioMed Central 2021-11-04 /pmc/articles/PMC8567681/ /pubmed/34736529 http://dx.doi.org/10.1186/s13073-021-00977-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mitra, Anita
MacIntyre, David A.
Paraskevaidi, Maria
Moscicki, Anna-Barbara
Mahajan, Vishakha
Smith, Ann
Lee, Yun S.
Lyons, Deirdre
Paraskevaidis, Evangelos
Marchesi, Julian R.
Bennett, Phillip R.
Kyrgiou, Maria
The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
title The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
title_full The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
title_fullStr The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
title_full_unstemmed The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
title_short The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
title_sort vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567681/
https://www.ncbi.nlm.nih.gov/pubmed/34736529
http://dx.doi.org/10.1186/s13073-021-00977-w
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