PDF(Pubmed)
Abstract：
BACKGROUND: Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. The endometrial cancer microbiome has been poorly characterised so far and studies have often overestimated bacterial biomass due to lack of integration of appropriate contamination controls. There is also a scarcity of evidence on the functionality of microbial microenvironments in endometrial cancer. This work addresses that knowledge gap by interrogating the genuine, contamination-free microbial signatures in the female genital tract and rectum of women with endometrial cancer and the mechanistic role of microbiome on carcinogenic processes.
RESULTS: Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) and rectum of 61 patients (37 endometrial cancer; 24 benign controls). We performed 16S rRNA gene sequencing of the V1-V2 hypervariable regions and qPCR of the 16S rRNA gene to qualitatively and quantitatively assess microbial communities and used 3D benign and endometrial cancer organoids to evaluate the effect of microbial products of L. crispatus, which was found depleted in endometrial cancer patients following primary analysis, on endometrial cell proliferation and inflammation. We found that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus, increased bacterial diversity and enrichment of Porphyromonas, Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media exerted an anti-proliferative effect at high concentrations but had minimal impact on cytokine and chemokine profiles.
CONCLUSIONS: Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology and what is the functional significance of this finding remain to be elucidated to guide future screening tools and microbiome-based therapeutics. Video Abstract.
RESULTS: Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) and rectum of 61 patients (37 endometrial cancer; 24 benign controls). We performed 16S rRNA gene sequencing of the V1-V2 hypervariable regions and qPCR of the 16S rRNA gene to qualitatively and quantitatively assess microbial communities and used 3D benign and endometrial cancer organoids to evaluate the effect of microbial products of L. crispatus, which was found depleted in endometrial cancer patients following primary analysis, on endometrial cell proliferation and inflammation. We found that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus, increased bacterial diversity and enrichment of Porphyromonas, Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media exerted an anti-proliferative effect at high concentrations but had minimal impact on cytokine and chemokine profiles.
CONCLUSIONS: Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology and what is the functional significance of this finding remain to be elucidated to guide future screening tools and microbiome-based therapeutics. Video Abstract.
摘要：
背景：子宫内膜癌是一种多因素的炎症性疾病，代谢和潜在的微生物线索参与疾病的发病机制。迄今为止，子宫内膜癌微生物组的特征很少，并且由于缺乏适当的污染控制措施，研究常常高估了细菌生物量。关于子宫内膜癌中微生物微环境的功能的证据也很少。这项工作通过询问真实的，子宫内膜癌女性生殖道和直肠中无污染的微生物特征以及微生物组对致癌过程的机制作用。
结果：在这里，我们对生殖道的不同区域（阴道，子宫颈,子宫内膜,61例患者的输卵管和卵巢）和直肠（37例子宫内膜癌；24例良性对照）。我们对V1-V2高变区进行了16SrRNA基因测序，并对16SrRNA基因进行了qPCR，以定性和定量评估微生物群落，并使用3D良性和子宫内膜癌类器官来评估卷曲乳杆菌微生物产物的作用。主要分析后发现子宫内膜癌患者耗尽，子宫内膜细胞增殖和炎症。我们发现，患有和不患有子宫内膜癌的女性的上生殖道在数量和组成上都具有与背景污染物不同的微生物群。子宫内膜癌与宫颈阴道和直肠细菌负荷减少以及乳酸杆菌相对丰度的消耗有关。包括柳条,增加细菌多样性和卟啉菌的富集，普雷沃氏菌,下生殖道和子宫内膜的嗜肽和厌氧球菌。用crispatus条件培养基治疗良性和恶性子宫内膜类器官在高浓度下具有抗增殖作用，但对细胞因子和趋化因子谱的影响最小。
结论：我们的发现提供了证据，表明一些女性的上生殖道含有可检测水平的细菌，其组成与子宫内膜癌有关。这是癌症病理生理学的原因还是结果，以及这一发现的功能意义还有待阐明，以指导未来的筛查工具和基于微生物组的疗法。视频摘要。
结果：在这里，我们对生殖道的不同区域（阴道，子宫颈,子宫内膜,61例患者的输卵管和卵巢）和直肠（37例子宫内膜癌；24例良性对照）。我们对V1-V2高变区进行了16SrRNA基因测序，并对16SrRNA基因进行了qPCR，以定性和定量评估微生物群落，并使用3D良性和子宫内膜癌类器官来评估卷曲乳杆菌微生物产物的作用。主要分析后发现子宫内膜癌患者耗尽，子宫内膜细胞增殖和炎症。我们发现，患有和不患有子宫内膜癌的女性的上生殖道在数量和组成上都具有与背景污染物不同的微生物群。子宫内膜癌与宫颈阴道和直肠细菌负荷减少以及乳酸杆菌相对丰度的消耗有关。包括柳条,增加细菌多样性和卟啉菌的富集，普雷沃氏菌,下生殖道和子宫内膜的嗜肽和厌氧球菌。用crispatus条件培养基治疗良性和恶性子宫内膜类器官在高浓度下具有抗增殖作用，但对细胞因子和趋化因子谱的影响最小。
结论：我们的发现提供了证据，表明一些女性的上生殖道含有可检测水平的细菌，其组成与子宫内膜癌有关。这是癌症病理生理学的原因还是结果，以及这一发现的功能意义还有待阐明，以指导未来的筛查工具和基于微生物组的疗法。视频摘要。
