DataSheet_1_Changes in the Vaginal Microbiome and Associated Toxicities Following Radiation Therapy for Gynecologic Cancers.xlsx

Postmenopausal women often suffer from vaginal symptoms associated with atrophic vaginitis. Additionally, gynecologic cancer survivors may live for decades with additional, clinically significant, persistent vaginal toxicities caused by cancer therapies, including pain, dyspareunia, and sexual dysfunction. The vaginal microbiome (VM) has been previously linked with vaginal symptoms related to menopause (i.e. dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women, with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association between the dynamics and structure of the vaginal microbiome with the manifestation and persistence of vaginal symptoms, during one year after completion of cancer therapies, while controlling for clinical and sociodemographic factors. We compared cross-sectionally the vaginal microbiome in 134 women, 64 gynecologic patients treated with radiotherapy and 68 healthy controls, and we longitudinally followed a subset of 52 women quarterly (4 times in a year: pre-radiation therapy, 2, 6 and 12 months post-therapy). Differences among the VM profiles of cancer and healthy women were more pronounced with the progression of time. Cancer patients had higher diversity VMs and a variety of vaginal community types (CTs) that are not dominated by Lactobacilli, with extensive VM variation between individuals. Additionally, cancer patients exhibit highly unstable VMs (based on Bray-Curtis distances) compared to healthy controls. Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%) and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%) and dyspareunia (32%) were equally or more prominent in healthy women at baseline. However, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability; for example, patients with persistent dryness or abnormally high pH have the most unstable microbiomes. Associations were identified between vaginal symptoms and individual bacterial taxa, including: Prevotella with vaginal dryness, Delftia with pain following vaginal intercourse, and Gemillaceaea with low levels of lubrication during intercourse. Taken together our results indicate that gynecologic cancer therapy is associated with reduced vaginal microbiome stability and vaginal symptom persistence.

绝经后女性常罹患与萎缩性阴道炎相关的阴道症状。此外，妇科癌症幸存者可能在数十年间持续受到癌症治疗引发的、具有临床意义的持续性阴道毒性反应困扰，包括疼痛、性交痛与性功能障碍。阴道微生物组（vaginal microbiome, VM）此前已被证实与绝经相关阴道症状（如干涩）存在关联。我们此前的研究表明，妇科癌症患者的阴道微生物组特征与健康女性存在显著差异：其乳酸杆菌丰度较低，且多种机会致病性细菌更为流行。本研究旨在探究癌症治疗结束后一年内，阴道微生物组的动态变化与组成结构，与阴道症状的发生及持续状态之间的关联，并控制临床与社会人口学因素的影响。本研究对134名女性的阴道微生物组进行了横断面比较：其中包括64名接受放疗的妇科癌症患者与68名健康对照；同时对其中52名女性进行了为期一年的季度性纵向随访（共4次采样：放疗前、治疗后2、6及12个月）。随着时间推移，癌症患者与健康女性的阴道微生物组特征差异愈发显著。癌症患者的阴道微生物组多样性更高，且存在多种不以乳酸杆菌为优势菌的阴道菌群类型（vaginal community types, CTs），个体间的微生物组差异也更为显著。此外，与健康对照相比，癌症患者的阴道微生物组稳定性极差（基于Bray-Curtis距离计算）。癌症患者中常见的阴道症状包括阴道疼痛（40%）、出血（35%）、阴道痉挛（28%）与炎症（20%）；而健康女性在基线时的干涩（45%）、润滑不足（33%）及性交痛（32%）等症状的发生率则与之相当甚至更高。但有24%的癌症患者在所有随访时间点均持续出现阴道症状，而健康女性中这一比例仅为12%。症状持续状态与阴道微生物组稳定性呈显著负相关：例如，持续出现干涩或阴道pH异常升高的患者，其微生物组稳定性最差。研究还发现阴道症状与特定细菌类群存在关联：普雷沃菌属（Prevotella）与阴道干涩相关，代尔夫特菌属（Delftia）与性交后疼痛相关，而吉米菌科（Gemillaceaea）则与性交时润滑不足相关。综合以上结果，本研究表明妇科癌症治疗与阴道微生物组稳定性下降及阴道症状持续存在显著相关。