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

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Title: The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia
Authors: Mitra, A
MacIntyre, DA
Paraskevaidi, M
Moscicki, A-B
Mahajan, V
Smith, A
Lee, YS
Lyons, D
Paraskevaidis, E
Marchesi, JR
Bennett, PR
Kyrgiou, M
Item Type: Journal Article
Abstract: 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.
Issue Date: 4-Nov-2021
Date of Acceptance: 23-Sep-2021
URI: http://hdl.handle.net/10044/1/92662
DOI: 10.1186/s13073-021-00977-w
ISSN: 1756-994X
Publisher: BioMed Central
Journal / Book Title: Genome Medicine: medicine in the post-genomic era
Volume: 13
Issue: 1
Copyright Statement: © The Author(s) 2021. 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 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/. The Creative Commons Public Domain Dedication waiver (http://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.
Sponsor/Funder: Imperial College Healthcare Charity
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Vaginal microbiota
Metataxonomics
Mucosal immunity
Cervical intraepithelial neoplasia
Lactobacillus
HUMAN-PAPILLOMAVIRUS INFECTION
LEUKOCYTE PROTEASE INHIBITOR
LARGE LOOP EXCISION
ANTIMICROBIAL PEPTIDE
INCOMPLETE EXCISION
BACTERIAL VAGINOSIS
TRANSFORMATION ZONE
IFN-GAMMA
WOMEN
ASSOCIATION
Cervical intraepithelial neoplasia
Lactobacillus
Metataxonomics
Mucosal immunity
Vaginal microbiota
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Vaginal microbiota
Metataxonomics
Mucosal immunity
Cervical intraepithelial neoplasia
Lactobacillus
HUMAN-PAPILLOMAVIRUS INFECTION
LEUKOCYTE PROTEASE INHIBITOR
LARGE LOOP EXCISION
ANTIMICROBIAL PEPTIDE
INCOMPLETE EXCISION
BACTERIAL VAGINOSIS
TRANSFORMATION ZONE
IFN-GAMMA
WOMEN
ASSOCIATION
0604 Genetics
1103 Clinical Sciences
Publication Status: Published
Article Number: ARTN 176
Appears in Collections:Department of Metabolism, Digestion and Reproduction



This item is licensed under a Creative Commons License Creative Commons