背景:慢性盆腔疼痛(CPP)是一种多因素综合征,可显著影响患者的生活质量。子宫内膜异位症是CPP的病因之一,在子宫内膜异位症患者中观察到免疫和微生物组的变化。这项初步研究的目的是研究与无子宫内膜异位症和无CPP的CPP患者相比,有CPP和子宫内膜异位症诊断的患者的阴道和胃肠道微生物组和宫颈阴道免疫微环境的差异。
方法:阴道拭子,直肠拭子,收集接受妇科腹腔镜检查的患者的宫颈阴道灌洗(CVL)。参与者根据寻求慢性疼痛和/或病理结果的患者进行分组:CPP和子宫内膜异位症(CPP-Endo)(n=35),CPP无子宫内膜异位症(n=23),或无CPP或子宫内膜异位症的患者(对照)(n=15)。对具有子宫内膜异位症位置的CPP进行敏感性分析,舞台,和同时发生的妇科疾病(异常子宫出血,肌瘤)。进行16SrRNA测序以描述微生物组,和一组可溶性免疫介质使用多重测定进行定量。采用SAS进行统计分析,R,MicrobiomeAnalyst,MetaboAnalyst,和QIIME2。
结果:观察到单独使用CPP的参与者之间存在显着差异,CPP-Endo,以及体重指数的手术控制,种族,卵巢囊肿的诊断,和肌瘤的诊断。在直肠微生物组分析中,单独的CPP和CPP-Endo都表现出比对照更低的α多样性,两个CPP组都显示肠易激综合征相关细菌富集。CPP-Endo表现出增加的阴道性链球菌和直肠Ruminococus的丰度。CPP和子宫内膜瘤患者表现出增加的阴道链球菌,乳酸菌,和普雷沃氏菌与其他子宫内膜异位症部位相比。Further,异常子宫出血与细菌性阴道病相关细菌丰度增加相关.与对照相比,免疫蛋白质组谱通过单独的CPP和CPP-Endo明显聚集。CPP-Endo富含TNF,MDC,和IL-1。
结论:在单纯CPP患者和有子宫内膜异位症的CPP患者之间,观察到阴道和直肠微生物组存在差异,这可能是有用的个性化治疗从那些与CPP的其他原因患有CPP和子宫内膜异位症。进一步的调查是必要的患者有额外的共同发生的条件,如AUB/肌瘤,这增加了这些条件的额外复杂性,并揭示了不同的病原细菌在两个粘膜部位的富集。这项研究提供了与慢性盆腔疼痛相关的基础微生物组-免疫蛋白质组学知识,子宫内膜异位症,以及同时发生的妇科疾病,可以帮助改善寻求疼痛护理的患者的治疗。
BACKGROUND: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient\'s quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP.
METHODS: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding,
fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2.
RESULTS: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of
fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺.
CONCLUSIONS: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/
fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.