PDF(Sci-hub)
Abstract：
BACKGROUND: The gut microbiota may influence the risk of breast cancer through effects on endogenous estrogens.
OBJECTIVE: The objective of the study was to investigate whether urinary estrogens and estrogen metabolites are associated with the diversity and composition of the fecal microbiome.
METHODS: This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado.
METHODS: A total of 60 women drawn from a random sample of healthy postmenopausal women (aged 55-69 y), without current or recent use of antibiotics or hormone therapy and no history of cancer or gastrointestinal disease participated in the study. OUTCOME MEASURES AND METHODS: Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity and composition of the fecal microbiome with parent estrogen (estrone + estradiol), total estrogens, and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer risk in previous studies.
RESULTS: The ratio of metabolites to parents was directly associated with whole-tree phylogenetic diversity (R = 0.35, P = .01). Relative abundances of the order Clostridiales (R = 0.32, P = .02) and the genus Bacteroides (R = -0.30, P = .03) were also correlated with the ratio of metabolites to parents. Associations were independent of age, body mass index, and study design factors.
CONCLUSIONS: Our data suggest that women with a more diverse gut microbiome exhibit an elevated urinary ratio of hydroxylated estrogen metabolites to parent estrogen. Further research is warranted to confirm and relate these findings to clinical disease.
OBJECTIVE: The objective of the study was to investigate whether urinary estrogens and estrogen metabolites are associated with the diversity and composition of the fecal microbiome.
METHODS: This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado.
METHODS: A total of 60 women drawn from a random sample of healthy postmenopausal women (aged 55-69 y), without current or recent use of antibiotics or hormone therapy and no history of cancer or gastrointestinal disease participated in the study. OUTCOME MEASURES AND METHODS: Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity and composition of the fecal microbiome with parent estrogen (estrone + estradiol), total estrogens, and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer risk in previous studies.
RESULTS: The ratio of metabolites to parents was directly associated with whole-tree phylogenetic diversity (R = 0.35, P = .01). Relative abundances of the order Clostridiales (R = 0.32, P = .02) and the genus Bacteroides (R = -0.30, P = .03) were also correlated with the ratio of metabolites to parents. Associations were independent of age, body mass index, and study design factors.
CONCLUSIONS: Our data suggest that women with a more diverse gut microbiome exhibit an elevated urinary ratio of hydroxylated estrogen metabolites to parent estrogen. Further research is warranted to confirm and relate these findings to clinical disease.
摘要：
背景：肠道菌群可能通过对内源性雌激素的影响影响乳腺癌的风险。
目的：本研究的目的是调查尿雌激素和雌激素代谢产物是否与粪便微生物组的多样性和组成相关。
方法：这是一项在科罗拉多州KaiserPermanente注册的女性的横断面研究。
方法：从健康绝经后妇女（年龄55-69岁）的随机抽样中抽取60名妇女，目前或近期未使用抗生素或激素治疗,且无癌症或胃肠道疾病史参与研究.结果测量和方法：通过液相色谱-串联质谱法测定尿中肌酐标准化的尿雌激素（雌酮和雌二醇）和13种羟基化的雌激素代谢产物。使用16SrRNA扩增子的焦磷酸测序评估粪便微生物组。一般线性模型用于测试粪便微生物组的多样性和组成与母体雌激素（雌酮雌二醇）的关联。总雌激素，和雌激素代谢物以及雌激素代谢物与母体雌激素的比例，在以前的研究中，这已经预测了绝经后乳腺癌的风险。
结果：代谢物与亲本的比例与全树系统发育多样性直接相关（R=0.35，P=0.01）。梭菌属（R=0.32，P=.02）和拟杆菌属（R=-0.30，P=.03）的相对丰度也与代谢物与亲本的比率相关。协会与年龄无关，身体质量指数,并研究设计因素。
结论：我们的数据表明，肠道微生物组更加多样化的女性表现出尿中羟基化雌激素代谢产物与母体雌激素的比例升高。需要进一步的研究来证实这些发现并将其与临床疾病联系起来。
目的：本研究的目的是调查尿雌激素和雌激素代谢产物是否与粪便微生物组的多样性和组成相关。
方法：这是一项在科罗拉多州KaiserPermanente注册的女性的横断面研究。
方法：从健康绝经后妇女（年龄55-69岁）的随机抽样中抽取60名妇女，目前或近期未使用抗生素或激素治疗,且无癌症或胃肠道疾病史参与研究.结果测量和方法：通过液相色谱-串联质谱法测定尿中肌酐标准化的尿雌激素（雌酮和雌二醇）和13种羟基化的雌激素代谢产物。使用16SrRNA扩增子的焦磷酸测序评估粪便微生物组。一般线性模型用于测试粪便微生物组的多样性和组成与母体雌激素（雌酮雌二醇）的关联。总雌激素，和雌激素代谢物以及雌激素代谢物与母体雌激素的比例，在以前的研究中，这已经预测了绝经后乳腺癌的风险。
结果：代谢物与亲本的比例与全树系统发育多样性直接相关（R=0.35，P=0.01）。梭菌属（R=0.32，P=.02）和拟杆菌属（R=-0.30，P=.03）的相对丰度也与代谢物与亲本的比率相关。协会与年龄无关，身体质量指数,并研究设计因素。
结论：我们的数据表明，肠道微生物组更加多样化的女性表现出尿中羟基化雌激素代谢产物与母体雌激素的比例升高。需要进一步的研究来证实这些发现并将其与临床疾病联系起来。
