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

Genome Medicine

Deirdre Lyons¹  Evangelos Paraskevaidis²  Julian R. Marchesi³  Ann Smith⁴  Vishakha Mahajan⁵  Maria Paraskevaidi⁵  David A. MacIntyre⁵  Yun S. Lee⁵  Anita Mitra⁶  Phillip R. Bennett⁶  Maria Kyrgiou⁷  Anna-Barbara Moscicki⁸ 

[1] Department of Obstetrics & Gynaecology, Imperial College NHS Trust, W120HS, London, UK;Department of Obstetrics & Gynaecology, Imperial College NHS Trust, W120HS, London, UK;Department of Obstetrics and Gynaecology, University Hospital of Ioannina, Ioannina, Greece;Division of Digestive Diseases, Imperial College London, W2 1NY, London, UK;Faculty of Health and Applied Sciences, University West of England, Bristol, Glenside Campus, BS16 1DD, Bristol, UK;Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction – Surgery and Cancer, Imperial College London, W12 0NN, London, UK;Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction – Surgery and Cancer, Imperial College London, W12 0NN, London, UK;Department of Obstetrics & Gynaecology, Imperial College NHS Trust, W120HS, London, UK;Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction – Surgery and Cancer, Imperial College London, W12 0NN, London, UK;Department of Obstetrics & Gynaecology, Imperial College NHS Trust, W120HS, London, UK;IRDB, Department of Gut, Metabolism and Reproduction - Surgery and Cancer, Imperial College London, Hammersmith Campus, 3rd Floor, Du Cane Road, W12 0NN, London, UK;Ronald Reagan UCLA Medical Center, UCLA Mattel Children’s Hospital, Santa Monica, CA, USA;

关键词: Vaginal microbiota;    Metataxonomics;    Mucosal immunity;    Cervical intraepithelial neoplasia;    Lactobacillus;   

DOI  :  10.1186/s13073-021-00977-w

来源: Springer

【 摘 要 】

BackgroundVaginal 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.MethodsWe 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.ResultsWomen 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.ConclusionsWomen 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.

【 授权许可】

CC BY