Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wenhuaxi Road, Jinan, Shandong 250012, China.
Cryomedicine Lab, Qilu Hospital of Shandong University, No. 107 Wenhuaxi Road, Jinan, Shandong 250012, China.
Hum Reprod. 2018 Apr 1;33(4):607-616. doi: 10.1093/humrep/dex372.
What happens to the gut microbiota during development of murine endometriosis?
Mice with the persistence of endometrial lesions for 42 days develop a distinct composition of gut microbiota.
Disorders in the immune system play fundamental roles in changing the intestinal microbiota. No study has used high-throughput DNA sequencing to show how endometriosis changes the gut microbiota, although endometriosis is accompanied by abnormal cytokine expression and immune cell dysfunction.
STUDY DESIGN, SIZE, DURATION: This study includes a prospective and randomized experiment on an animal endometriosis model induced via the intraperitoneal injection of endometrial tissues.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The mice were divided into endometriosis and mock groups and were sacrificed at four different time points for model confirmation and fecal sample collection. To detect gut microbiota, 16S ribosomal-RNA gene sequencing was performed. Alpha diversity was used to analyze the complexity and species diversity of the samples through six indices. Beta diversity analysis was utilized to evaluate the differences in species complexity. Principal coordinate analysis and unweighted pair-group method with arithmetic means clustering were performed to determine the clustering features. The microbial features differentiating the fecal microbiota were characterized by linear discriminant analysis effect size method.
The endometriosis and mock mice shared similar diversity and richness of gut microbiota. However, different compositions of gut microbiota were detected 42 days after the modeling. Among the discriminative concrete features, the Firmicutes/Bacteroidetes ratio was elevated in mice with endometriosis, indicating that endometriosis may induce dysbiosis. Bifidobacterium, which is known as a commonly used probiotic, was also increased in mice with endometriosis.
N/A.
LIMITATIONS, REASONS FOR CAUTION: More control groups should be further studied to clarify the specificity of the dysbiosis induced by endometriosis. This study was performed only on mice. Thus, additional data acquired from patients with endometriosis are needed in future research. We only detected the changes of gut microbiota at 42 days after the modeling, while the long-term effect of endometriosis on gut microbiota remains poorly understood. Moreover, we only revealed a single effect of endometriosis on gut microbiota.
This study provided the first comprehensive data on the association of endometriosis and gut microbiota from high-throughput sequencing technology. The gut microbiota changed with the development of endometriosis in a murine model. The communication between the host and the gut microbiota is bidirectional, and further studies should be performed to clarify their relationship.
STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Grant (81571417) from the National Science Foundation of China and Grant (2015GSF118092) from the Technology Development Plan of Shandong Province. The authors report no conflict of interest.
在小鼠子宫内膜异位症发展过程中,肠道微生物群会发生什么变化?
患有子宫内膜病变 42 天的小鼠会产生独特的肠道微生物群组成。
免疫系统紊乱在改变肠道微生物群方面起着至关重要的作用。尽管子宫内膜异位症伴随着异常的细胞因子表达和免疫细胞功能障碍,但尚无研究使用高通量 DNA 测序来显示子宫内膜异位症如何改变肠道微生物群,尽管子宫内膜异位症伴随着异常的细胞因子表达和免疫细胞功能障碍。
研究设计、大小、持续时间:这是一项在通过腹腔内注射子宫内膜组织诱导的动物子宫内膜异位症模型上进行的前瞻性、随机实验。
参与者/材料、设置、方法:将小鼠分为子宫内膜异位症组和模拟组,并在四个不同时间点进行模型确认和粪便样本采集。为了检测肠道微生物群,进行了 16S 核糖体 RNA 基因测序。通过六个指标的 alpha 多样性分析来评估样本的复杂性和物种多样性。利用 beta 多样性分析评估物种复杂性的差异。主坐标分析和不带权重的分组方法与算术平均值聚类用于确定聚类特征。通过线性判别分析效应量方法对区分粪便微生物群的微生物特征进行了表征。
子宫内膜异位症和模拟小鼠的肠道微生物群具有相似的多样性和丰富度。然而,在建模 42 天后检测到不同的肠道微生物群组成。在区分具体特征中,患有子宫内膜异位症的小鼠的厚壁菌门/拟杆菌门比值升高,表明子宫内膜异位症可能导致肠道菌群失调。双歧杆菌是一种常用的益生菌,在患有子宫内膜异位症的小鼠中也增加了。
无。
局限性、谨慎的原因:需要进一步研究更多的对照组,以明确子宫内膜异位症引起的菌群失调的特异性。本研究仅在小鼠中进行,因此,未来的研究需要来自子宫内膜异位症患者的更多数据。我们仅在建模后 42 天检测到肠道微生物群的变化,而子宫内膜异位症对肠道微生物群的长期影响仍知之甚少。此外,我们只揭示了子宫内膜异位症对肠道微生物群的单一影响。
本研究首次从高通量测序技术提供了子宫内膜异位症与肠道微生物群关联的全面数据。在小鼠模型中,肠道微生物群随着子宫内膜异位症的发展而变化。宿主与肠道微生物群之间的交流是双向的,需要进一步研究以阐明它们之间的关系。
研究资助/利益冲突:本研究得到国家自然科学基金(81571417)和山东省技术发展计划(2015GSF118092)的支持。作者没有报告利益冲突。