Probiotic Bifidobacterium lactis V9 Regulates the Secretion of Sex Hormones in Polycystic Ovary Syndrome Patients through the Gut-Brain Axis
Probiotic Bifidobacterium lactis V9 Regulates the Secretion of Sex Hormones in Polycystic Ovary Syndrome Patients through the Gut-Brain Axis
复制标题
益生菌乳双歧杆菌 V9 通过肠脑轴调节多囊卵巢综合症患者性激素的分泌
DOI：
10.1128/msystems.00017-19
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发表时间：
2019-03-01
期刊：
影响因子：
6.4
通讯作者：
Zhang, Heping
中科院分区：
文献类型：
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作者：
Zhang, Jiachao;Sun, Zhihong;Zhang, Heping
多囊卵巢综合征（PCOS）是一种常见的代谢紊乱的育龄妇女在世界各地。通过两阶段的临床实验，我们首次揭示了PCOS患者肠道微生物组的不平衡。通过将鸟枪法宏基因组序列分箱和注释到宏基因组物种（MGS）中，61个MGS被鉴定为潜在的PCOS相关微生物生物标志物。在第二阶段，我们监测了益生菌乳酸双歧杆菌V9对PCOS患者肠道菌群、代谢参数、肠脑介质和性激素的影响。值得注意的是，我们观察到参与患者的PCOS相关临床指标和肠道微生物菌群对B摄入的反应不一致。乳酸菌V9益生菌。因此，益生菌的有效宿主肠道定殖对其作为益生菌发挥功能的能力至关重要。最后，我们提出了一个潜在的机制，其中B。lactis V9通过操纵PCOS患者的肠道微生物组来调节性激素水平。摘要虽然一些研究调查了多囊卵巢综合征（PCOS）妇女的肠道微生物群，但与PCOS相关的微生物的功能和代谢机制以及潜在的微生物生物标志物尚未确定。为了解决这一差距，我们设计了一个两阶段的实验，在这个实验中，我们进行了鸟枪宏基因组测序，并监测了PCOS患者的代谢参数，肠-脑介质和性激素。在第一阶段，我们确定了PCOS患者肠道微生物群的不平衡，观察到粪杆菌属，双歧杆菌属和布劳特氏菌属在对照组中明显更丰富，而副拟杆菌属和梭菌属在PCOS组中富集。在第二阶段，我们监测了益生菌乳酸双歧杆菌V9对14名PCOS患者的肠道微生物组，肠脑介质和性激素的影响。值得注意的是，我们观察到9名志愿者的促黄体生成素（LH）和LH/促卵泡激素（LH/FSH）水平显著下降，而性激素和肠道短链脂肪酸（SCFAs）水平显著升高。而其余5名志愿者上述指标变化不明显。两组中活乳双歧杆菌V9细胞数量的分析结果与临床和SCFA结果高度一致。因此，益生菌乳酸双歧杆菌V9的有效宿主肠道定殖对于其作为益生菌发挥功能的能力至关重要。最后，我们提出了一种潜在的机制，描述了益生菌如何通过操纵PCOS患者的肠道微生物组来调节性激素水平。多囊卵巢综合征（PCOS）是一种常见的代谢性疾病。通过两阶段的临床实验，我们首次揭示了PCOS患者肠道微生物组的不平衡。通过将鸟枪法宏基因组序列分箱和注释到宏基因组物种（MGS）中，61个MGS被鉴定为潜在的PCOS相关微生物生物标志物。在第二阶段，我们监测了益生菌乳酸双歧杆菌V9对PCOS患者肠道菌群、代谢参数、肠脑介质和性激素的影响。值得注意的是，我们观察到参与患者的PCOS相关临床指标和肠道微生物菌群对B摄入的反应不一致。乳酸菌V9益生菌。因此，益生菌的有效宿主肠道定殖对其作为益生菌发挥功能的能力至关重要。最后，我们提出了一个潜在的机制，其中B。lactis V9通过操纵PCOS患者的肠道微生物组来调节性激素水平。
Polycystic ovary syndrome (PCOS) is a common metabolic disorder among women of reproductive age worldwide. Through a two-phase clinical experiment, we first revealed an imbalance in the intestinal microbiome of PCOS patients. By binning and annotating shotgun metagenomic sequences into metagenomic species (MGS), 61 MGSs were identified as potential PCOS-related microbial biomarkers. In the second stage, we monitored the impact of the probiotic Bifidobacterium lactis V9 on the intestinal microbiota, metabolic parameters, gut-brain mediators, and sex hormones of PCOS patients. Notably, we observed that the PCOS-related clinical indices and the intestinal microbiotas of the participating patients exhibited an inconsistent response to the intake of the B. lactis V9 probiotic. Therefore, effective host gut colonization of the probiotic was crucial for its ability to function as a probiotic. Finally, we propose a potential mechanism by which B. lactis V9 regulates the levels of sex hormones by manipulating the intestinal microbiome in PCOS patients. ABSTRACT Although a few studies have investigated the intestinal microbiota of women with polycystic ovary syndrome (PCOS), the functional and metabolic mechanisms of the microbes associated with PCOS, as well as potential microbial biomarkers, have not yet been identified. To address this gap, we designed a two-phase experiment in which we performed shotgun metagenomic sequencing and monitored the metabolic parameters, gut-brain mediators, and sex hormones of PCOS patients. In the first stage, we identified an imbalance in the intestinal microbiota of the PCOS patients, observing that Faecalibacterium, Bifidobacterium, and Blautia were significantly more abundant in the control group, whereas Parabacteroides and Clostridium were enriched in the PCOS group. In the second stage, we monitored the impact of the probiotic Bifidobacterium lactis V9 on the intestinal microbiome, gut-brain mediators, and sex hormones of 14 PCOS patients. Notably, we observed that the levels of luteinizing hormone (LH) and LH/follicle-stimulating hormone (LH/FSH) decreased significantly in 9 volunteers, whereas the levels of sex hormones and intestinal short-chain fatty acids (SCFAs) increased markedly. In contrast, the changes in the indices mentioned above were indistinct in the remaining 5 volunteers. The results of an analysis of the number of viable Bifidobacterium lactis V9 cells in the two groups were highly consistent with the clinical and SCFA results. Therefore, effective host gut colonization of the probiotic Bifidobacterium lactis V9 was crucial for its ability to function as a probiotic. Finally, we propose a potential mechanism describing how probiotics regulate the levels of sex hormones by manipulating the intestinal microbiome in PCOS patients. IMPORTANCE Polycystic ovary syndrome (PCOS) is a common metabolic disorder among women of reproductive age worldwide. Through a two-phase clinical experiment, we first revealed an imbalance in the intestinal microbiome of PCOS patients. By binning and annotating shotgun metagenomic sequences into metagenomic species (MGS), 61 MGSs were identified as potential PCOS-related microbial biomarkers. In the second stage, we monitored the impact of the probiotic Bifidobacterium lactis V9 on the intestinal microbiota, metabolic parameters, gut-brain mediators, and sex hormones of PCOS patients. Notably, we observed that the PCOS-related clinical indices and the intestinal microbiotas of the participating patients exhibited an inconsistent response to the intake of the B. lactis V9 probiotic. Therefore, effective host gut colonization of the probiotic was crucial for its ability to function as a probiotic. Finally, we propose a potential mechanism by which B. lactis V9 regulates the levels of sex hormones by manipulating the intestinal microbiome in PCOS patients.