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Article(id=1241771813873713372, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241771801366299468, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202404068, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1712073600000, receivedDateStr=2024-04-03, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773991071432, onlineDateStr=2026-03-20, pubDate=1729785600000, pubDateStr=2024-10-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773991071432, onlineIssueDateStr=2026-03-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773991071432, creator=13701087609, updateTime=1773991071432, updator=13701087609, issue=Issue{id=1241771801366299468, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='20', pageStart='3649', pageEnd='3840', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773991068450, creator=13701087609, updateTime=1773991676896, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241774353457681403, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241771801366299468, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241774353457681404, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241771801366299468, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=3816, endPage=3822, ext={EN=ArticleExt(id=1241771814960038132, articleId=1241771813873713372, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Mendelian randomization analysis of gut microbiota-mediated effects of testosterone on endometriosis, columnId=null, journalTitle=Modern Preventive Medicine, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective

To explore the causal relationship between testosterone and endometriosis, andto identify and quantify the role of gut microbiota as a potential mediator through Mendelian randomization analysis.

Methods

Utilizing the summary data from the IEU GWAS database for testosterone (n=199 569) and endometriosis (8 288 cases and 68 969 controls) as the exposure and outcome variables, and the aggregated gut microbiota data from the MiBioGen Consortium (n=18 340) as the mediator, a bidirectional, two-step Mendelian randomization analysis was conducted. Causal relationships were assessed using inverse varianceweighted, MR-Egger, weighted median, weighted model, and simple modelto assess causality, while sensitivity analysis was conducted to ensure the robustness of the findings.

Results

Impact of testosterone on endometriosis:Inverse variance weighted estimates suggested that testosterone had negative causal effects on endometriosis (OR=0.804, 95%CI:0.670-0.964, P=0.018).Impact of endometriosis on testosterone:Reverse Mendelian randomization showed that endometriosis did not present a causal effect on testosterone (OR=0.991, 95%CI:0.958-1.026, P=0.616).The class Melainabacteria, one of the gut microbiotas, accounted for a 17.21% reduction in the risk of endometriosis associated with testosterone (mediation proportion: 17.21%, 95%CI:0.090-0.264, P=0.035).

Conclusion

Testosterone is one of the protective factors of endometriosis.Low testosterone levels increase the risk of endometriosis.Gut microbiota may be a mediator of the causal effect of testosterone on endometriosis.

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目的

基于孟德尔随机化分析探讨睾酮和子宫内膜异位症之间的因果关系，并确定和量化肠道菌群作为潜在介质的作用。

方法

使用IEUGWAS数据库中的睾酮（n=199 569）和子宫内膜异位症（病例组8 288例，对照组68 969例）的汇总数据分别作为暴露和结局，MiBioGen联盟的肠道菌群汇总数据（n=18 340）作为中介，进行双向、两步法孟德尔随机化分析。采用逆方差加权法、MR-Egger回归法、加权中位数法、加权模型法和简单模型法评估因果关系，敏感性分析检验结果是否稳健。

结果

逆方差加权法显示睾酮与子宫内膜异位症呈负向因果关系（OR=0.804，95% CI:0.670~0.964，P=0.018）；反向孟德尔随机化显示，子宫内膜异位症对睾酮不呈现因果效应（OR=0.991，95% CI:0.958~1.026，P=0.616）；肠道菌群中的黑色杆菌纲占睾酮（中介占比：17.21%，95% CI:0.090~0.264，P=0.035）相关的子宫内膜异位症风险降低的17.21%。

结论

睾酮是子宫内膜异位症的保护性因素之一，睾酮水平低会增加子宫内膜异位症的患病风险。肠道菌群可能是睾酮对子宫内膜异位症因果关系的中介因素。

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马秀丽，E-mail：
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点，除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=EFkTDq8AagLxTNdnrNLx+Q==, magXml=W9/C4EXMoFl583Vkx8JV0A==, pdfUrl=null, pdf=hkGUrQV07EbNMqdrhlG2hg==, pdfFileSize=1093901, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=Z6JECsuKgMfX7Hh/pUV7Cg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=aQD5s2BgS/Pn6j1d98WThA==, mapNumber=null, authorCompany=null, fund=null, authors=

李晓颖（1999—），女，硕士在读，研究方向：女性盆腔痛症的中医药治疗、宫颈HPV感染的中西医结合治疗

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李晓颖（1999—），女，硕士在读，研究方向：女性盆腔痛症的中医药治疗、宫颈HPV感染的中西医结合治疗

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李晓颖（1999—），女，硕士在读，研究方向：女性盆腔痛症的中医药治疗、宫颈HPV感染的中西医结合治疗

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Pathogenesis of endometriosis: the origin of pain and subfertility[J]. Cells (Basel, Switzerland), 2021, 10(6): 1381., articleTitle=Pathogenesis of endometriosis: the origin of pain and subfertility, refAbstract=null), Reference(id=1241771828956431185, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2021, volume=397, issue=10276, pageStart=839, pageEnd=852, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=Taylor HS, Kotlyar AM, Flores VA, journalName=Lancet, refType=null, unstructuredReference=Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations[J]. Lancet, 2021, 397(10276): 839-852., articleTitle=Endometriosis is a chronic systemic disease: clinical challenges and novel innovations, refAbstract=null), Reference(id=1241771829057094487, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2023, volume=29, issue=6, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=Lissaman AC, Girling JE, Cree LM, journalName=Molecular Human Reproduction, refType=null, unstructuredReference=Lissaman AC, Girling JE, Cree LM, et al. Androgen signalling in the ovaries and endometrium[J]. Molecular Human Reproduction, 2023, 29(6): gaad017., articleTitle=Androgen signalling in the ovaries and endometrium, refAbstract=null), Reference(id=1241771829161952089, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2020, volume=246, issue=3, pageStart=R75, pageEnd=R93, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=Gibson DA, Simitsidellis I, Collins F, journalName=Journal of Endocrinology, refType=null, unstructuredReference=Gibson DA, Simitsidellis I, Collins F, et al. Androgens, oestrogens and endometrium: a fine balance between perfection and pathology[J]. Journal of Endocrinology, 2020, 246(3): R75-R93., articleTitle=Androgens, oestrogens and endometrium: a fine balance between perfection and pathology, refAbstract=null), Reference(id=1241771829258421085, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2021, volume=3, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=Evans SF, Hull ML, Hutchinson MR, journalName=Frontiers in Reproductive Health, refType=null, unstructuredReference=Evans SF, Hull ML, Hutchinson MR, et al. Androgens, endometriosis and pain[J]. Frontiers in Reproductive Health, 2021, 3: 792920., articleTitle=Androgens, endometriosis and pain, refAbstract=null), Reference(id=1241771829354890080, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2023, volume=108, issue=1, pageStart=72, pageEnd=80, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=Bishop CV, Takahashi DL, Luo FZ, journalName=Biology of Reproduction, refType=null, unstructuredReference=Bishop CV, Takahashi DL, Luo FZ, et al. The combined impact of testosterone and western-style diet on endometriosis severity and progression in rhesus macaques†[J]. Biology of Reproduction, 2023, 108(1): 72-80., articleTitle=The combined impact of testosterone and western-style diet on endometriosis severity and progression in rhesus macaques†, refAbstract=null), Reference(id=1241771829468136294, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2024, volume=14, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=Tang F, Deng MQ, Xu CY, journalName=Frontiers in Cellular and Infection Microbiology, refType=null, unstructuredReference=Tang F, Deng MQ, Xu CY, et al. Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis[J]. Frontiers in Cellular and Infection Microbiology, 2024, 14: 1328419., articleTitle=Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis, refAbstract=null), Reference(id=1241771829577188205, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2020, volume=27, issue=4, pageStart=1064, pageEnd=1073, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=Perrotta AR, Borrelli GM, Martins CO, journalName=Reproductive Sciences, refType=null, unstructuredReference=Perrotta AR, Borrelli GM, Martins CO, et al. The vaginal microbiome as a Tool to predict rASRM stage of disease in endometriosis: a pilot study[J]. Reproductive Sciences, 2020, 27(4): 1064-1073., articleTitle=The vaginal microbiome as a Tool to predict rASRM stage of disease in endometriosis: a pilot study, refAbstract=null), Reference(id=1241771829694628717, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2021, volume=304, issue=5, pageStart=1363, pageEnd=1373, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=Shan J, Ni ZX, Cheng W, journalName=Archives of Gynecology and Obstetrics, refType=null, unstructuredReference=Shan J, Ni ZX, Cheng W, et al. Gut microbiota imbalance and its correlations with hormone and inflammatory factors in patients with stage 3/4 endometriosis[J]. Archives of Gynecology and Obstetrics, 2021, 304(5): 1363-1373., articleTitle=Gut microbiota imbalance and its correlations with hormone and inflammatory factors in patients with stage 3/4 endometriosis, refAbstract=null), Reference(id=1241771829812069232, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2023, volume=35, issue=4, pageStart=473, pageEnd=476, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=李应雯, 刘敏, 袁浩, journalName=中国微生态学杂志, refType=null, unstructuredReference=李应雯，刘敏，袁浩，等．睾酮与肠道菌群关系的研究进展[J]．中国微生态学杂志，2023，35（4）：473-476．, articleTitle=睾酮与肠道菌群关系的研究进展, refAbstract=null), Reference(id=1241771829996618610, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2023, volume=35, issue=4, pageStart=473, pageEnd=476, url=null, language=null, rfNumber=[10], rfOrder=10, authorNames=Li YW, Liu M, Yuan H, journalName=Chinese Journal of Microecology, refType=null, unstructuredReference=Li YW, Liu M, Yuan H, et al. Relationship between testosterone and intestinal flora:research progress[J]. Chinese Journal of Microecology, 2023, 35(4): 473-476. (In Chinese), articleTitle=Relationship between testosterone and intestinal flora:research progress, refAbstract=null), Reference(id=1241771830084698995, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2022, volume=41, issue=6, pageStart=1100, pageEnd=1119, url=null, language=null, rfNumber=[11], rfOrder=11, authorNames=Shapland CY, Zhao QY, Bowden J, journalName=Medicine Statistics, refType=null, unstructuredReference=Shapland CY, Zhao QY, Bowden J. Profile-likelihood Bayesian model averaging for two-sample summary data Mendelian randomization in the presence of horizontal pleiotropy[J]. Medicine Statistics, 2022, 41(6): 1100-1119., articleTitle=Profile-likelihood Bayesian model averaging for two-sample summary data Mendelian randomization in the presence of horizontal pleiotropy, refAbstract=null), Reference(id=1241771830193750902, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2021, volume=11, issue=1, pageStart=24, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=12, authorNames=Garitazelaia A, Rueda-Martínez A, Arauzo R, journalName=Life, refType=null, unstructuredReference=Garitazelaia A, Rueda-Martínez A, Arauzo R, et al. A systematic two-sample mendelian randomization analysis identifies shared genetic origin of endometriosis and associated phenotypes[J]. Life, 2021, 11(1): 24., articleTitle=A systematic two-sample mendelian randomization analysis identifies shared genetic origin of endometriosis and associated phenotypes, refAbstract=null), Reference(id=1241771830273442680, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2022, volume=54, issue=1, pageStart=52, pageEnd=61, url=null, language=null, rfNumber=[13], rfOrder=13, authorNames=Liu XM, Tong X, Zou YA, journalName=Nature Genetics, refType=null, unstructuredReference=Liu XM, Tong X, Zou YA, et al. Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome[J]. Nature Genetics, 2022, 54(1): 52-61., articleTitle=Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome, refAbstract=null), Reference(id=1241771830374105979, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2023, volume=13, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=14, authorNames=Zhai QL, Wu HY, Zheng SY, journalName=Frontiers in Cellular and Infection Microbiology, refType=null, unstructuredReference=Zhai QL, Wu HY, Zheng SY, et al. Association between gut microbiota and NAFLD/NASH: a bidirectional two-sample Mendelian randomization study[J]. Frontiers in Cellular and Infection Microbiology, 2023, 13: 1294826., articleTitle=Association between gut microbiota and NAFLD/NASH: a bidirectional two-sample Mendelian randomization study, refAbstract=null), Reference(id=1241771830495740798, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2023, volume=21, issue=1, pageStart=482, pageEnd=null, url=null, language=null, rfNumber=[15], rfOrder=15, authorNames=Mcgrath IM, Montgomery GW, Mortlock S, journalName=BMC Medicine, refType=null, unstructuredReference=Mcgrath IM, Montgomery GW, Mortlock S, et al. Polygenic risk score phenome-wide association study reveals an association between endometriosis and testosterone[J]. BMC Medicine, 2023, 21(1): 482., articleTitle=Polygenic risk score phenome-wide association study reveals an association between endometriosis and testosterone, refAbstract=null), Reference(id=1241771830592209792, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2021, volume=9, issue=1, pageStart=174, pageEnd=191, url=null, language=null, rfNumber=[16], rfOrder=16, authorNames=Dinsdale N, Nepomnaschy P, Crespi B, journalName=Evolution, Medicine, and Public Health, refType=null, unstructuredReference=Dinsdale N, Nepomnaschy P, Crespi B. The evolutionary biology of endometriosis[J]. Evolution, Medicine, and Public Health, 2021, 9(1): 174-191., articleTitle=The evolutionary biology of endometriosis, refAbstract=null), Reference(id=1241771830676095875, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2020, volume=2020, issue=3, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=17, authorNames=Crestani A, Arfi A, Ploteau S, journalName=Human Reproduction Open, refType=null, unstructuredReference=Crestani A, Arfi A, Ploteau S, et al. Anogenital distance in adult women is a strong marker of endometriosis: results of a prospective study with laparoscopic and histological findings[J]. Human Reproduction Open, 2020, 2020(3): hoaa023., articleTitle=Anogenital distance in adult women is a strong marker of endometriosis: results of a prospective study with laparoscopic and histological findings, refAbstract=null), Reference(id=1241771830768370567, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2022, volume=30, issue=3, pageStart=329, pageEnd=339.e5, url=null, language=null, rfNumber=[18], rfOrder=18, authorNames=Li D, Liu R, Wang M, journalName=Cell Host & Microbe, refType=null, unstructuredReference=Li D, Liu R, Wang M, et al. 3β-Hydroxysteroid dehydrogenase expressed by gut microbes degrades testosterone and is linked to depression in males[J]. Cell Host & Microbe, 2022, 30(3): 329-339.e5., articleTitle=3β-Hydroxysteroid dehydrogenase expressed by gut microbes degrades testosterone and is linked to depression in males, refAbstract=null), Reference(id=1241771830856450953, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2020, volume=11, issue=1, pageStart=4822, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=19, authorNames=Daisley BA, Chanyi RM, Abdur-Rashid K, journalName=Nature Communications, refType=null, unstructuredReference=Daisley BA, Chanyi RM, Abdur-Rashid K, et al. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients[J]. Nature Communications, 2020, 11(1): 4822., articleTitle=Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients, refAbstract=null), Reference(id=1241771830944531340, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2019, volume=64, issue=6, pageStart=889, pageEnd=898, url=null, language=null, rfNumber=[20], rfOrder=20, authorNames=Yao G, Wu SG, Zeng XC, journalName=Folia Microbiologica, refType=null, unstructuredReference=Yao G, Wu SG, Zeng XC, et al. Different gut microbiome composition in obese Guizhou minipigs between female and castrated male[J]. Folia Microbiologica, 2019, 64(6): 889-898., articleTitle=Different gut microbiome composition in obese Guizhou minipigs between female and castrated male, refAbstract=null), Reference(id=1241771831028417423, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, doi=null, pmid=null, pmcid=null, year=2021, volume=11, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=21, authorNames=Huang LJ, Liu BD, Liu ZH, journalName=Frontiers in Cellular and Infection Microbiology, refType=null, unstructuredReference=Huang LJ, Liu BD, Liu ZH, et al. Gut microbiota exceeds cervical microbiota for early diagnosis of endometriosis[J]. 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注：A为T与EMS的双向MR分析，c为T对EMS的总效应，d为EMS对T的总效应。B为两步法MR分析，a为T对GM的总效应, b为GM对EMS的总效应，c’为T对EMS的直接效应。

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注：图A为黑色杆菌纲；B为芽孢杆菌目；C为普氏菌科；D为厌氧菌属；E为反刍真杆菌属；F为欧陆森氏菌属；G为颤螺菌属。

, figureFileSmall=rY2FIfFDjcBieeLmMSeszg==, figureFileBig=67RnNfoaGo97sKgF1mLocw==, tableContent=null), ArticleFig(id=1241771826276270888, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=EN, label=Fig.7, caption=Forest plot of T and GM based on IVW, figureFileSmall=Y/Ze/WW5oJxFwhkimqRHBQ==, figureFileBig=t9FbuUPN2os99z01bA0oFQ==, tableContent=null), ArticleFig(id=1241771826406294315, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=CN, label=图7, caption=基于IVW法的T与GM的MR分析森林图, figureFileSmall=Y/Ze/WW5oJxFwhkimqRHBQ==, figureFileBig=t9FbuUPN2os99z01bA0oFQ==, tableContent=null), ArticleFig(id=1241771826502763311, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=EN, label=Table 1, caption=

ThecausalrelationshipbetweenTandEMS

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露结局SNPs数方法β标准误P值OR值（95%CI）
TEMS103IVW-0.2180.0930.0180.804（0.670~0.964）
MREgger-0.1650.1700.3340.848（0.608~1.182）
Weightedmedian-0.1340.1160.2500.875（0.697~1.098）
Simplemode-0.0190.2050.9250.981（0.656~1.466）
Weightedmode-0.1170.1050.2700.890（0.724~1.094）
), ArticleFig(id=1241771828016907058, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=CN, label=表1, caption=

T与EMS的因果关系

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露结局SNPs数方法β标准误P值OR值（95%CI）
TEMS103IVW-0.2180.0930.0180.804（0.670~0.964）
MREgger-0.1650.1700.3340.848（0.608~1.182）
Weightedmedian-0.1340.1160.2500.875（0.697~1.098）
Simplemode-0.0190.2050.9250.981（0.656~1.466）
Weightedmode-0.1170.1050.2700.890（0.724~1.094）
), ArticleFig(id=1241771828125958968, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=EN, label=Table 2, caption=

The results of sensitivity analysis on the relationship between T andEMS

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露结局异质性检验水平多效性检验
IVW法
QP值		MREgger
QP值		MREgger
intercep t值		MREgger
intercept P值
TEMS0.2200.2010.0010.854
EMST<0.001<0.0010.0090.314
), ArticleFig(id=1241771828255982395, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=CN, label=表2, caption=

T与EMS的敏感性分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露结局异质性检验水平多效性检验
IVW法
QP值		MREgger
QP值		MREgger
intercep t值		MREgger
intercept P值
TEMS0.2200.2010.0010.854
EMST<0.001<0.0010.0090.314
), ArticleFig(id=1241771828365034301, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=EN, label=Table 3, caption=

Results of reverse MR analysis between EMS and T

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露结局SNPs数方法β标准误P值OR值（95%CI）
EMST11IVW-0.0090.0170.6160.991（0.958~1.026）
MREgger-0.0660.0570.2720.936（0.838~1.046）
Weighted median-0.0070.0120.5610.993（0.970~1.017）
Simple mode-0.0170.0210.4470.983（0.944~1.025）
Weighted mode-0.0150.0190.4400.985（0.948~1.022）
), ArticleFig(id=1241771828478280514, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813873713372, language=CN, label=表3, caption=

EMS与T反向MR分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露结局SNPs数方法β标准误P值OR值（95%CI）
EMST11IVW-0.0090.0170.6160.991（0.958~1.026）
MREgger-0.0660.0570.2720.936（0.838~1.046）
Weighted median-0.0070.0120.5610.993（0.970~1.017）
Simple mode-0.0170.0210.4470.983（0.944~1.025）
Weighted mode-0.0150.0190.4400.985（0.948~1.022）
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肠道菌群介导睾酮对子宫内膜异位症影响的孟德尔随机化分析
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李晓颖 , 马秀丽 , 孙凌逸 , 李娜 , 阙绮莹 , 吴晓婷 , 仇梦
现代预防医学 | 临床与预防 2024,51(20): 3816-3822
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现代预防医学 | 临床与预防 2024, 51(20): 3816-3822
肠道菌群介导睾酮对子宫内膜异位症影响的孟德尔随机化分析
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李晓颖, 马秀丽 , 孙凌逸, 李娜, 阙绮莹, 吴晓婷, 仇梦
作者信息
  • 北京中医药大学东直门医院妇科,北京 100700

    • 李晓颖（1999—），女，硕士在读，研究方向：女性盆腔痛症的中医药治疗、宫颈HPV感染的中西医结合治疗

通讯作者:

马秀丽，E-mail：
Mendelian randomization analysis of gut microbiota-mediated effects of testosterone on endometriosis
Xiao-ying LI, Xiu-li MA , Ling-yi SUN, Na LI, Qi-ying QUE, Xiao-ting WU, Meng QIU
Affiliations
  • Obstetrics and Gynecology Department of Dongzhimen Hospital, Beijing University of Chinese Medicine, No 5, Dongcheng District, Beijing 100700, China
出版时间: 2024-10-25 doi: 10.20043/j.cnki.MPM.202404068
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摘要
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目的

基于孟德尔随机化分析探讨睾酮和子宫内膜异位症之间的因果关系，并确定和量化肠道菌群作为潜在介质的作用。

方法

使用IEUGWAS数据库中的睾酮（n=199 569）和子宫内膜异位症（病例组8 288例，对照组68 969例）的汇总数据分别作为暴露和结局，MiBioGen联盟的肠道菌群汇总数据（n=18 340）作为中介，进行双向、两步法孟德尔随机化分析。采用逆方差加权法、MR-Egger回归法、加权中位数法、加权模型法和简单模型法评估因果关系，敏感性分析检验结果是否稳健。

结果

逆方差加权法显示睾酮与子宫内膜异位症呈负向因果关系（OR=0.804，95% CI:0.670~0.964，P=0.018）；反向孟德尔随机化显示，子宫内膜异位症对睾酮不呈现因果效应（OR=0.991，95% CI:0.958~1.026，P=0.616）；肠道菌群中的黑色杆菌纲占睾酮（中介占比：17.21%，95% CI:0.090~0.264，P=0.035）相关的子宫内膜异位症风险降低的17.21%。

结论

睾酮是子宫内膜异位症的保护性因素之一，睾酮水平低会增加子宫内膜异位症的患病风险。肠道菌群可能是睾酮对子宫内膜异位症因果关系的中介因素。

孟德尔随机化  /  子宫内膜异位症  /  睾酮  /  肠道菌群  /  因果推断
Objective

To explore the causal relationship between testosterone and endometriosis, andto identify and quantify the role of gut microbiota as a potential mediator through Mendelian randomization analysis.

Methods

Utilizing the summary data from the IEU GWAS database for testosterone (n=199 569) and endometriosis (8 288 cases and 68 969 controls) as the exposure and outcome variables, and the aggregated gut microbiota data from the MiBioGen Consortium (n=18 340) as the mediator, a bidirectional, two-step Mendelian randomization analysis was conducted. Causal relationships were assessed using inverse varianceweighted, MR-Egger, weighted median, weighted model, and simple modelto assess causality, while sensitivity analysis was conducted to ensure the robustness of the findings.

Results

Impact of testosterone on endometriosis:Inverse variance weighted estimates suggested that testosterone had negative causal effects on endometriosis (OR=0.804, 95%CI:0.670-0.964, P=0.018).Impact of endometriosis on testosterone:Reverse Mendelian randomization showed that endometriosis did not present a causal effect on testosterone (OR=0.991, 95%CI:0.958-1.026, P=0.616).The class Melainabacteria, one of the gut microbiotas, accounted for a 17.21% reduction in the risk of endometriosis associated with testosterone (mediation proportion: 17.21%, 95%CI:0.090-0.264, P=0.035).

Conclusion

Testosterone is one of the protective factors of endometriosis.Low testosterone levels increase the risk of endometriosis.Gut microbiota may be a mediator of the causal effect of testosterone on endometriosis.

Mendelian randomization  /  Endometriosis  /  Testosterone  /  Gut microbiota  /  Causal inference
李晓颖, 马秀丽, 孙凌逸, 李娜, 阙绮莹, 吴晓婷, 仇梦. 肠道菌群介导睾酮对子宫内膜异位症影响的孟德尔随机化分析. 现代预防医学, 2024 , 51 (20) : 3816 -3822 . DOI: 10.20043/j.cnki.MPM.202404068
Xiao-ying LI, Xiu-li MA, Ling-yi SUN, Na LI, Qi-ying QUE, Xiao-ting WU, Meng QIU. Mendelian randomization analysis of gut microbiota-mediated effects of testosterone on endometriosis[J]. Modern Preventive Medicine, 2024 , 51 (20) : 3816 -3822 . DOI: 10.20043/j.cnki.MPM.202404068
正文
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子宫内膜异位症（Endometriosis,EMS）是一种常见的复杂的妇科疾病，是指当子宫腔内壁含有腺体、间质、血管及淋巴管等组织的粘膜层出现在子宫体以外的部位，并且生长、浸润、反复出血而导致的一系列病症[1]，育龄期女性患病率约为10%，常表现为不孕和疼痛[2]。目前经血逆流种植学说、淋巴及静脉播散学说、体腔上皮化生学说、免疫与炎症因素、遗传与环境因素等是已经提出的可能导致EMS的理论和假说，然而EMS的发病机制迄今为止尚不明确。
睾酮（Testosterone,T）是雄激素之一，少量存在于女性体内，其受体在月经周期的不同阶段具有差异性表达，对子宫内膜生物学具有重要的调控作用[3]。EMS病灶虽然具有雌激素依赖性特征，但即使在循环雌激素水平受抑制的情况下，病灶仍然可能维持生长状态[4]。有研究表明T水平异常低下可能会增加罹患EMS的风险或加剧已存在的症状[5]。而一部分研究却发现高水平的T可能通过代谢功能障碍间接导致EMS患病风险增加[6]。因此，T与EMS之间的关系尚未明确，其具体机制还需进一步研究。
人类肠道中栖息着庞大且复杂的生态微生物群落，随着对肠道菌群（gutmicrobiota,GM）研究的逐渐深入，越来越多的研究报道了GM失衡可以通过多种途径促进异位病灶的血管生成和侵袭生长[7]。而一项收集了深度3cm直肠拭子的研究却发现，EMS患者和对照组之间的GM没有差异[8]。此外，T通过肝肠循环被重吸收入血，其变化可能会直接影响GM的分布，失调的GM可能导致肠粘膜通透性增高，脂多糖进入血液循环，激活免疫细胞，释放炎症因子，影响免疫微环境，引发全身慢性炎症反应，进而导致异位病灶的粘附、侵袭和生长[9-10]。总之，T、GM与EMS之间密切相关，基于目前的研究我们推测T水平可能通过引起GM的改变，致使EMS的发生与进展。然而，T诱导疾病发生的机制尚未十分明确，且GM自身具有复杂性，是否为T与EMS之间的潜在中介因子还需更深入地研究与探讨。
孟德尔随机化（MendelianRandomization,MR）以遗传学作为工具变量来评估暴露因素与结局之间的因果关系，而遗传变异与后代无关且随机分配，因此MR分析提供了一种不受混杂因素的影响，可以评估因果序列的新方法[11]。本文采用MR分析的目的是确定T与EMS之间是否存在因果关系，并评估GM介导T对EMS影响的中介效应，以期为预防和治疗EMS提供新的视角。
1　材料和方法
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1.1　研究设计
T和EMS分别作为暴露和结局变量进行双向两样本MR分析推断暴露和结局的因果关系。将GM作为暴露因素、EMS作为结局变量，T作为暴露因素、GM作为结局变量，进行两步法MR分析推断可能存在的中介因素。敏感性分析评估结果的可靠性。具体见图1。
1.2　数据来源
EMS和T的大规模全基因组关联研究（genome-wideassociationstudy，GWAS）数据来源于英国布里斯托尔大学整合流行病学单位开发的IEUOpenGWAS数据库（https://gwas.mrcieu.ac.uk/），其中EMS的GWASID为：finnb-N14_ENDOMETRIOSIS[12] ，研究使用了芬兰生物银行国家网络收集的样本，由欧洲血统的8 288例病例和68 969例对照组成，共有16 377 306个单核苷酸多态性 （singlenucleotidepolymorphisms,SNPs）。T的GWASID为ieu-b-4864，来自一项检测了199 569名欧洲女性T水平的研究，包括12 321 875个SNPs。
GM数据来自MiBioGen联盟（https://mibiogen.gcc.rug.nl/）的GWAS汇总数据。包括来自24个不同队列的18 340名个体，其中欧洲血统的参与者有13 266人。本文排除了3个未知科与12个未知属共15个没有特定名称的GM，最终纳入9门、32科、20目、16纲和119属共196种细菌进行分析。
文中使用的汇总数据均来源于可免费下载的已获得伦理批准的公共数据，本研究不需要单独的伦理批准。
1.3　工具变量的筛选
本研究利用GWAS数据，筛选暴露中符合条件的SNPs作为工具变量进行MR分析，依赖于3个核心假设：①关联性假设：最终纳入的工具变量和暴露强相关；②独立性假设：工具变量独立于已知的混杂因素；③排他性假设：工具变量不能直接影响结果，只通过暴露因素影响结果。
因此，为了保证研究结果的全面性和准确性，预先根据以下步骤对T、EMS及GM分别作为暴露数据时进行筛选：（1）选择与暴露具有强相关性（P<5×10-8）的SNPs；（2）为了保证初步筛选的SNPs位点之间相互独立，避免连锁不平衡（Linkagedisequilibrium，LD）的产生，进一步设置参数r2<0.001，物理距离=10 000 kb；（3）删除缺失等位基因的SNPs和回文SNPs；（4）使用F统计量评估工具变量的强度，
公式为：
其中N为暴露的总样本数，K为筛选出的SNPs个数，R2是SNPs解释暴露的程度。MAF是最小等位基因频率,在计算R2时可以和效应等位基因频率等价，β为等位基因效应值，s是β的标准误，剔除F<10的SNPs避免弱工具变量偏倚；（5）应用MR-PRESSO法用于检验异常值，比较去除异常值前后的因果估计差异，剔除工具变量中离群值，矫正水平多效性后再进行MR分析。
由于GM样本量较少，根据以上标准预先筛选后的符合P<5×10-8、r2<0.001，物理距离=10 000 kb的工具变量极少，为了增加统计功效以获得更全面的研究结果，我们将GM数据的显著性阈值调整为P<1×10-5[13]，同时以r2<0.01,物理距离=10 000 kb[14]进行去LD分析以获得更具包容性的结果。
1.4　MR分析
本研究应用逆方差加权（Inverse variance weighted，IVW）法作为主要MR分析方法，MR-Egger回归法、加权中位数法（Weighted median）、加权模型法（Weighted mode）和简单模型法（Simple mode）作为补充方法分析暴露与结局的因果效应。结果用比值比（odds ratio，OR）和95%置信区间（95%confidence interval，95%CI）表示，检验水准α=0.05。两步法MR分析的总体效应可以分解为直接效应（不通过中介）效应和间接效应（通过中介），如图2所示，T对EMS的总效应c分解为T对EMS的直接效应（c’=c-a×b）和T通过中介变量（a×b）介导的间接效应。中介效应占比为间接效应除以总效应，同时用系数乘积法计算95%CI。
1.5　敏感性分析
为了评估MR分析因果效应的稳健性，进行敏感性分析揭示可能存在的干扰因素提升结果的可信度和解释力。Cochran Q检验用于评估选定SNPs之间的异质性，P>0.05代表不存在异质性，选择固定效应IVW模型，否则应用随机效应IVW模型。MR-Egger截距用于检验水平多效性，P>0.05表示不存在水平多效性。留一法分析通过移除单个SNP来判断是否存在具有强影响的SNPs，导致IVW法估计值被其影响,以检验数据是否稳定。
所有数据分析用R语言（4.2.2版）软件的“TwoSampleMR”（0.5.8版）、“MR-PRESSO”程序包进行。
2　结果
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2.1　双向MR分析结果
2.1.1　T对EMS的影响
基于工具变量的筛选标准，剔除MR-PRESSO检验提示的两个异常值rs11031005、rs7521867，共获得103个SNPs，IVW法显示T与EMS呈负向因果关系（OR=0.804，95% CI:0.670~0.964，P=0.018），差异有显著性意义。5种MR分析结果见表1；散点图见图3。
敏感性分析Cochran Q检验结果表明，工具变量之间不存在明显的异质性；MR-Egger截距结果未表现出水平多效性，IVW法可以作为分析因果关系的主要标准，见表2。留一法分析结果未见明显离群值，表明研究结果的可靠性。漏斗图中显示的因果效应分布基本对称，进一步说明了上述结果的稳定性，不受潜在因素影响而发生偏倚，见图4。
2.1.2　反向MR分析结果
五种方法均提示EMS对T无因果关系（P>0.05），详见表3。MR-PRESSO方法没有检测到潜在的异常值。敏感性分析Cochran Q检验P<0.05，表明存在异质性，采用随机效应模型进行分析。MR-Egger截距的P值>0.05，证明水平多效性不显著。
2.2　两步法MR分析结果
2.2.1　GM对EMS的影响
为了探索T对EMS的因果效应机制，以GM为中介进行两步法MR分析。将GM作为暴露，EMS作为结局，196个GM共获得了2151个SNPs，9门（106个SNPs）、16纲（191个SNPs）、20目（234个SNPs）、32科（370个SNPs）和119属（1250个SNPs）。共得到7个细菌类群的84个SNPs可能与EMS有关，包括1 纲（10个SNPs）、1目（9个SNPs）、1科（16个SNPs）和4属（49个SNPs）。分别是黑色杆菌纲（classMelainabacteria）、芽孢杆菌目（orderBacillales）、普氏菌科（family Prevotellaceae）、厌氧菌属（genusAnaerotruncus）、反刍真杆菌属（genusEubacteriumruminantiumgroup）、欧陆森氏菌属（genusOlsenella）、颤螺菌属（genus Oscillospira）。
IVW法显示芽孢杆菌目（OR=1.106，95% CI：1.004~1.218，P=0.042）、普氏菌科（OR=1.194，95% CI：1.021~1.397，P=0.026）、厌氧菌属（OR=1.252，95% CI：1.028~1.525，P=0.025）、欧陆森氏菌属（OR=1.110，95% CI：1.007~1.223，P=0.036）、颤螺菌属（OR=1.215，95% CI：1.014~1.456，P=0.035）与EMS呈正相关；黑色杆菌纲（OR=0.863，95% CI：0.752~0.991，P=0.037）、反刍真杆菌属（OR=0.881，95% CI：0.795~0.976，P=0.015）与EMS呈负相关，MR分析结果见图5，散点图见图6。敏感性分析未表现出明显的异质性和水平多效性。
2.2.2　T对GM的影响
以T为暴露，与EMS相关的7种GM为结局的MR分析结果见图7。IVW法显示T与黑色杆菌纲（OR=1.290，95% CI：1.101~1.512，P=0.002）呈显著正相关。敏感性分析没有表现明显的异质性与水平多效性。
2.2.3　GM介导的T与EMS之间的关联比例
两步法MR分析揭示了T对黑色杆菌纲（P<0.05；β>0）的正因果效应和黑色杆菌纲对EMS（P<0.05；β<0）的负因果效应，提示GM中的黑色杆菌纲是连接T与EMS的一个重要中介变量，占T（间接效应β=-0.038，中介占比：17.21%，95%CI=0.090~0.264，P=0.035）相关的EMS风险降低的17.21%。
3　讨论
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本研究借助MR分析从遗传角度预测T与EMS的因果关系及可能存在的中介因素，结果显示T与EMS之间存在负向因果关系，表明T低水平可能与EMS的患病风险增加有关，T可能是EMS的保护性因素之一。反向MR结果显示，EMS对T无因果关系，没有强有力的证据表明EMS对T有影响。两步法MR分析提示，GM中的黑色杆菌纲可能是T和EMS因果关系中的重要中介因素。此外，芽孢杆菌目、普氏菌科、厌氧菌属、欧陆森氏菌属、颤螺菌属与EMS呈正向因果关系；黑色杆菌纲、反刍真杆菌属与EMS呈负向因果关系。
既往有研究探讨了T和EMS之间的关系，提示T水平低可能对EMS产生影响。一项基于英国生物银行进行的多基因风险评分研究指出，性别特异性在EMS的遗传倾向性中占据了核心地位，而这种差异可能是由T决定的[15]。有学者提出了EMS可能由产前T低水平引起的假说。胎儿期较低的T暴露水平还表现在女性较短的肛门与外生殖器之间的距离[16]，并且临床和超声检查证据也表明这与EMS的患病风险增加有关[17]。我们的研究进一步证实了T水平低会增加EMS的患病风险。T在体内主要由肝脏代谢，其代谢产物通过胆汁排入肠道，如果仍然具有生物活性，可能会通过肠壁再次被重新吸收回血液，最终通过粪便或尿液排出体外，因此T与GM存在着密切的关系[18]。GM的多样性和组成同样受到性别的影响，并且与性激素的差异有关。T水平低可以改变GM的分布。分析雄激素剥夺法治疗前列腺癌患者的GM发现，其体内的棒状杆菌属减少，嗜黏蛋白阿克曼氏菌增加[19]。一项动物实验对去势公猪与母猪的GM组成和功能进行测序，在两组内均观察到厚壁菌门/拟杆菌门比例增加[20]。同时，越来越多的观察性研究和实验认为GM的生态平衡失调会促进EMS的进展。Shan等[9]发现EMS患者的GM多样性降低，厚壁菌门/拟杆菌门比率升高，普氏菌7号是最丰富的分类单元。Huang等[21]发现EMS患者粪便和腹腔液中的微生物群落特征显著，具有分泌脂多糖潜能的革兰阴性菌，如假单胞菌科和普氏菌科丰度明显增加。脂多糖是一种由革兰阴性菌产生的内毒素，研究显示EMS小鼠的GM失衡可以损伤肠壁屏障，显著增加腹腔内的脂多糖水平，通过门静脉系统与免疫细胞上的Toll样受体4结合，激活NF-κB炎性通道，释放炎症因子，导致局部甚至全身的免疫炎症反应[22]。GM还可以影响T淋巴细胞分化，从而引起机体免疫反应的变化，其中Th17细胞在EMS患者的腹腔液中显著增加，影响异位病灶的免疫微环境，进而影响疾病的发生和发展[23]。
本文的优势在于目前尚未有关于GM介导T对EMS影响的报道。首次利用双向两样本MR分析和两步法MR分析探索GM是否介导了两者的因果关系；其次，利用公开数据库进行两样本MR分析，从基因层面探讨T和EMS之间的因果关系，不受反向因果和潜在混杂因素的影响，同时避免了人力物力财力的浪费等。
本研究存在以下几个方面的局限性。本文使用的GWAS数据绝大多数为欧洲人群，可能产生由于人口分层导致的工具变量偏差，不适用于其他人群；其次，GM的GWAS数据集中样本数较少，阈值调低后可能存在混杂因素，增加假阳性结果和多效性问题的风险，希望将来有更大的GWAS数据可供验证；第三，结果提示GM介导的中介占比较低，需要进行更多的研究探索其他潜在的危险因素可能作为中介。
综上所述，MR分析发现T是EMS的保护因素，T水平低会增加EMS的患病风险，此外，GM可能是T和EMS因果关系中的中介因素。EMS的发生和发展是一个复杂的病理过程，涉及遗传、免疫、内分泌、生活方式和环境因素等诸多方面的相互作用，本研究为后续深入探索EMS的发病机制、优化诊断方式及治疗方法提供了新的思路和方向。
基金
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  • 国家自然科学基金面上项目(81774360)
  • 北京中医药大学东直门医院2023科技创新专项(DZMKJCX-2023-006)
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参考文献 引证文献
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[1]
ruber TM, Mechsner S. Pathogenesis of endometriosis: the origin of pain and subfertility[J]. Cells (Basel, Switzerland), 2021, 10(6): 1381.
[2]
Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations[J]. Lancet, 2021, 397(10276): 839-852.
[3]
Lissaman AC, Girling JE, Cree LM, et al. Androgen signalling in the ovaries and endometrium[J]. Molecular Human Reproduction, 2023, 29(6): gaad017.
[4]
Gibson DA, Simitsidellis I, Collins F, et al. Androgens, oestrogens and endometrium: a fine balance between perfection and pathology[J]. Journal of Endocrinology, 2020, 246(3): R75-R93.
[5]
Evans SF, Hull ML, Hutchinson MR, et al. Androgens, endometriosis and pain[J]. Frontiers in Reproductive Health, 2021, 3: 792920.
[6]
Bishop CV, Takahashi DL, Luo FZ, et al. The combined impact of testosterone and western-style diet on endometriosis severity and progression in rhesus macaques†[J]. Biology of Reproduction, 2023, 108(1): 72-80.
[7]
Tang F, Deng MQ, Xu CY, et al. Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis[J]. Frontiers in Cellular and Infection Microbiology, 2024, 14: 1328419.
[8]
Perrotta AR, Borrelli GM, Martins CO, et al. The vaginal microbiome as a Tool to predict rASRM stage of disease in endometriosis: a pilot study[J]. Reproductive Sciences, 2020, 27(4): 1064-1073.
[9]
Shan J, Ni ZX, Cheng W, et al. Gut microbiota imbalance and its correlations with hormone and inflammatory factors in patients with stage 3/4 endometriosis[J]. Archives of Gynecology and Obstetrics, 2021, 304(5): 1363-1373.
[10]
李应雯，刘敏，袁浩，等．睾酮与肠道菌群关系的研究进展[J]．中国微生态学杂志，2023，35（4）：473-476．
Li YW, Liu M, Yuan H, et al. Relationship between testosterone and intestinal flora:research progress[J]. Chinese Journal of Microecology, 2023, 35(4): 473-476. (In Chinese)
[11]
Shapland CY, Zhao QY, Bowden J. Profile-likelihood Bayesian model averaging for two-sample summary data Mendelian randomization in the presence of horizontal pleiotropy[J]. Medicine Statistics, 2022, 41(6): 1100-1119.
[12]
Garitazelaia A, Rueda-Martínez A, Arauzo R, et al. A systematic two-sample mendelian randomization analysis identifies shared genetic origin of endometriosis and associated phenotypes[J]. Life, 2021, 11(1): 24.
[13]
Liu XM, Tong X, Zou YA, et al. Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome[J]. Nature Genetics, 2022, 54(1): 52-61.
[14]
Zhai QL, Wu HY, Zheng SY, et al. Association between gut microbiota and NAFLD/NASH: a bidirectional two-sample Mendelian randomization study[J]. Frontiers in Cellular and Infection Microbiology, 2023, 13: 1294826.
[15]
Mcgrath IM, Montgomery GW, Mortlock S, et al. Polygenic risk score phenome-wide association study reveals an association between endometriosis and testosterone[J]. BMC Medicine, 2023, 21(1): 482.
[16]
Dinsdale N, Nepomnaschy P, Crespi B. The evolutionary biology of endometriosis[J]. Evolution, Medicine, and Public Health, 2021, 9(1): 174-191.
[17]
Crestani A, Arfi A, Ploteau S, et al. Anogenital distance in adult women is a strong marker of endometriosis: results of a prospective study with laparoscopic and histological findings[J]. Human Reproduction Open, 2020, 2020(3): hoaa023.
[18]
Li D, Liu R, Wang M, et al. 3β-Hydroxysteroid dehydrogenase expressed by gut microbes degrades testosterone and is linked to depression in males[J]. Cell Host & Microbe, 2022, 30(3): 329-339.e5.
[19]
Daisley BA, Chanyi RM, Abdur-Rashid K, et al. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients[J]. Nature Communications, 2020, 11(1): 4822.
[20]
Yao G, Wu SG, Zeng XC, et al. Different gut microbiome composition in obese Guizhou minipigs between female and castrated male[J]. Folia Microbiologica, 2019, 64(6): 889-898.
[21]
Huang LJ, Liu BD, Liu ZH, et al. Gut microbiota exceeds cervical microbiota for early diagnosis of endometriosis[J]. Frontiers in Cellular and Infection Microbiology, 2021, 11: 788836.
[22]
Ni ZX, Ding J, Zhao QQ, et al. Alpha-linolenic acid regulates the gut microbiota and the inflammatory environment in a mouse model of endometriosis[J]. American Journal of Reproductive Immunology, 2021, 86(4): e13471.
[23]
Guo CS, Zhang CY. Role of the gut microbiota in the pathogenesis of endometriosis: a review[J]. Frontiers in Microbiology, 2024, 15: 1363455.
2024年第51卷第20期
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doi: 10.20043/j.cnki.MPM.202404068
  • 接收时间：2024-04-03
  • 首发时间：2026-03-20
  • 出版时间：2024-10-25
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  • 收稿日期：2024-04-03
基金
国家自然科学基金面上项目(81774360)
北京中医药大学东直门医院2023科技创新专项(DZMKJCX-2023-006)
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    北京中医药大学东直门医院妇科,北京 100700

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马秀丽，E-mail：
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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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