首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1240651442298606214, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240651438955754377, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202403026, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1709222400000, receivedDateStr=2024-03-01, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773723954033, onlineDateStr=2026-03-17, pubDate=1719244800000, pubDateStr=2024-06-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773723954033, onlineIssueDateStr=2026-03-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773723954033, creator=13701087609, updateTime=1773723954033, updator=13701087609, issue=Issue{id=1240651438955754377, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='12', pageStart='2113', pageEnd='2912', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773723953236, creator=13701087609, updateTime=1773723953236, updator=13701087609, preIssue=null, nextIssue=null, ext=null, issueFiles=null}, startPage=2140, endPage=2145, ext={EN=ArticleExt(id=1240651443967939232, articleId=1240651442298606214, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Causal relationship between gut microbiota and uterine fibroids: a Mendelian randomization study, columnId=1228016567443718970, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods Advances, runingTitle=null, highlight=null, articleAbstract=
Objective

To assess the potential causal relationship between gut microbiota and the risk of uterine fibroids using a Mendelian randomization approach.

Methods

We used the genome-wide association study (GWAS) statistics of gut microbiota published by the Netherlands Microbiome Project in 2022 (n=7 738) and the GWAS data of uterine fibroids from the Finnish R9 database (31 661 uterine fibroid patients and 179 209 controls). Inverse variance weighting (IVW), MR-Egger regression and weighted median method were used to study the causal relationship between intestinal flora and uterine fibroids. Sensitivity analyses were performed to test the reliability of the results of the Mendelian randomization analysis.

Results

IVW results showed that Bacteroides (OR=1.045, 95%CI: 1.006-1.085), Ruminococcaceae (OR=1.119, 95%CI: 1.027-1.219), Roseobacter(OR=1.074, 95%CI: 1.004-1.149), Lactobacillus (OR=1.066, 95%CI: 1.017-1.118) and Firmicutes (OR=1.052, 95%CI: 1.003-1.102) were positively correlated with the incidence of uterine fibroids. No significant statistical difference was foundafter FDR correction (P>0.05).Bifidobacterium was negatively correlated with the incidence of uterine fibroids (OR=0.952,95%CI: 0.921-0.985). The causal association was statistically significant after FDR correction (P<0.05). No significant heterogeneity and horizontal pleiotropy were found in the sensitivity analysis.

Conclusion

Bifidobacterium may be a protective factor for the pathogenesis of uterine fibroids, while Bacteroides, Ruminococcaceae, Roseobacter, Lactobacillus and Firmicutes may be a potential risk factor for the pathogenesis of uterine fibroids. However, more studies are needed to verify the results. This study provides information about the microbiota that can be further studied, which is expected to improve the incidence and prognosis of uterine fibroids.

, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Wei LIANG, Ying LU, Xiao-xiao ZHANG, Xin GONG), CN=ArticleExt(id=1240651445662438150, articleId=1240651442298606214, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=肠道菌群与子宫肌瘤因果关系的孟德尔随机化研究, columnId=1228016567632462653, journalTitle=现代预防医学, columnName=流行病与统计方法, runingTitle=null, highlight=null, articleAbstract=
目的

采用孟德尔随机化方法来评估肠道菌群与子宫肌瘤风险之间的潜在因果关系。

方法

使用2022年荷兰微生物项目组发布的肠道菌群全基因组关联研究（GWAS）统计数据（n=7 738例）和芬兰R9数据库中子宫肌瘤的GWAS数据（31 661例子宫肌瘤患者和179 209例对照）。采用逆方差加权法（IVW）、MR-Egger回归法、加权中位数法来研究肠道菌群与子宫肌瘤之间的因果关系。敏感性分析用于检验孟德尔随机化分析结果是否可靠。

结果

IVW的结果显示肠道拟杆菌（OR=1.045，95%CI：1.006~1.085）、瘤胃球菌科（OR=1.119，95%CI：1.027~1.219）、罗氏菌属（OR=1.074，95%CI：1.004~1.149）、乳杆菌目（OR=1.066，95%CI：1.017~1.118）和厚壁菌（OR=1.052，95%CI：1.003~1.102）与子宫肌瘤的发病呈正相关，经FDR矫正后P>0.05，并未发现显著的统计学差异。而链状双歧杆菌（OR=0.952，95%CI：0.921~0.985）与子宫肌瘤的发病呈负相关，经FDR校正后P<0.05，表明二者之间的因果关联具有统计学意义。敏感性分析均未发现存在显著异质性和水平多效性。

结论

链状双歧杆菌可能是子宫肌瘤发病的保护因素，肠道拟杆菌、瘤胃球菌科、罗氏菌属、乳杆菌目和厚壁菌可能是子宫肌瘤发病的潜在危险因素，但有待更多研究进行验证。本研究提供了可进一步研究的菌群信息，这有望改善子宫肌瘤的发病与预后。

, correspAuthors=null, authorNote=null, correspAuthorsNote=
贡欣，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=CHDZgw75DrQF2LMm7FMkcA==, magXml=n8wcon/H6fdVbnqhbSeaMQ==, pdfUrl=null, pdf=9c78BIakxlRUVNka26o67w==, pdfFileSize=999361, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=TJ9vx9bgJesOfDknZXPQrA==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=WD1FVh8XPf1vAAHwtonxLw==, mapNumber=null, authorCompany=null, fund=null, authors=

梁伟（1999—），女，硕士在读，研究方向：中西医结合防治生殖内分泌疾病

, authorsList=梁伟, 卢英, 张晓晓, 贡欣)}, authors=[Author(id=1240651446186726200, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1240651446316749636, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651446186726200, language=EN, stringName=Wei LIANG, firstName=Wei, middleName=null, lastName=LIANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1240651447847670614, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651446186726200, language=CN, stringName=梁伟, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.北京中医药大学东方医院妇科，北京 100078, bio={"content":"

梁伟（1999—），女，硕士在读，研究方向：中西医结合防治生殖内分泌疾病

"}, bioImg=null, bioContent=

梁伟（1999—），女，硕士在读，研究方向：中西医结合防治生殖内分泌疾病

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1240651445960233761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, xref=1., ext=[AuthorCompanyExt(id=1240651445968622369, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China), AuthorCompanyExt(id=1240651445972816674, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.北京中医药大学东方医院妇科，北京 100078)])]), Author(id=1240651447973499743, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1240651448069968747, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651447973499743, language=EN, stringName=Ying LU, firstName=Ying, middleName=null, lastName=LU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1240651448158049143, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651447973499743, language=CN, stringName=卢英, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.北京中医药大学东方医院妇科，北京 100078, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1240651445960233761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, xref=1., ext=[AuthorCompanyExt(id=1240651445968622369, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China), AuthorCompanyExt(id=1240651445972816674, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.北京中医药大学东方医院妇科，北京 100078)])]), Author(id=1240651448283878274, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1240651448418096016, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651448283878274, language=EN, stringName=Xiao-xiao ZHANG, firstName=Xiao-xiao, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=null, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1240651448556508060, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651448283878274, language=CN, stringName=张晓晓, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2.北京中医药大学研究生院, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1240651446094451505, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, xref=2., ext=[AuthorCompanyExt(id=1240651446102840112, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651446094451505, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.北京中医药大学研究生院)])]), Author(id=1240651448682337188, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=zhongxiyigongxin@163.com, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1240651448816554933, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651448682337188, language=EN, stringName=Xin GONG, firstName=Xin, middleName=null, lastName=GONG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1240651448929801157, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, authorId=1240651448682337188, language=CN, stringName=贡欣, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.北京中医药大学东方医院妇科，北京 100078, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1240651445960233761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, xref=1., ext=[AuthorCompanyExt(id=1240651445968622369, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China), AuthorCompanyExt(id=1240651445972816674, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.北京中医药大学东方医院妇科，北京 100078)])])], keywords=[Keyword(id=1240651449072407511, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, orderNo=1, keyword=Uterine fibroids), Keyword(id=1240651449177265121, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, orderNo=2, keyword=Gut microbiota), Keyword(id=1240651449269539820, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, orderNo=3, keyword=Mendelian randomization), Keyword(id=1240651449412146163, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, orderNo=4, keyword=Genome-wide association study), Keyword(id=1240651449517003777, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, orderNo=5, keyword=Causal relationship), Keyword(id=1240651449634443269, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, orderNo=1, keyword=子宫肌瘤), Keyword(id=1240651449772855319, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, orderNo=2, keyword=肠道菌群), Keyword(id=1240651449902878754, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, orderNo=3, keyword=孟德尔随机化), Keyword(id=1240651450028707883, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, orderNo=4, keyword=全基因组关联研究), Keyword(id=1240651450179702842, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, orderNo=5, keyword=因果关系)], refs=[Reference(id=1240651453052801232, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2017, volume=124, issue=10, pageStart=1501, pageEnd=1512, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=Stewart EA, Cookson CL, Gandolfo RA, journalName=BJOG : an International Journal of Obstetrics and Gynaecology, refType=null, unstructuredReference=Stewart EA, Cookson CL, Gandolfo RA, et al. Epidemiology of uterine fibroids: a systematic review[J]. BJOG : an International Journal of Obstetrics and Gynaecology, 2017, 124(10): 1501-1512., articleTitle=Epidemiology of uterine fibroids: a systematic review, refAbstract=null), Reference(id=1240651453178630362, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2017, volume=52, issue=12, pageStart=793, pageEnd=800, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=子宫肌瘤的诊治中国专家共识专家组, journalName=中华妇产科杂志, refType=null, unstructuredReference=子宫肌瘤的诊治中国专家共识专家组．子宫肌瘤的诊治中国专家共识[J]．中华妇产科杂志，2017，52（12）：793-800．, articleTitle=子宫肌瘤的诊治中国专家共识, refAbstract=null), Reference(id=1240651453300265185, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2017, volume=52, issue=12, pageStart=793, pageEnd=800, url=null, language=null, rfNumber=[2], rfOrder=2, authorNames=Diagnosis and Treatment of Uterine Fibroids Chinese Expert Consensus Expert Group, journalName=Chinese Journal of Obstetrics and Gynecology, refType=null, unstructuredReference=Diagnosis and Treatment of Uterine Fibroids Chinese Expert Consensus Expert Group. Chinese expert consensus on the diagnosis and treatment of uterine fibroids[J]. Chinese Journal of Obstetrics and Gynecology, 2017, 52(12): 793-800., articleTitle=Chinese expert consensus on the diagnosis and treatment of uterine fibroids, refAbstract=null), Reference(id=1240651453447065839, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=140, issue=6, pageStart=1042, pageEnd=1048, url=null, language=null, rfNumber=[3], rfOrder=3, authorNames=Wegienka G, Havstad S, Coleman C, journalName=Obstetrics and Gynecology, refType=null, unstructuredReference=Wegienka G, Havstad S, Coleman C, et al. Ultrasound-confirmed, age-specific uterine leiomyoma incidence in a cohort of black individuals[J]. Obstetrics and Gynecology, 2022, 140(6): 1042-1048., articleTitle=Ultrasound-confirmed, age-specific uterine leiomyoma incidence in a cohort of black individuals, refAbstract=null), Reference(id=1240651453551923446, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2020, volume=189, issue=12, pageStart=1538, pageEnd=1546, url=null, language=null, rfNumber=[4], rfOrder=4, authorNames=Brasky TM, Bethea TN, Wesselink AK, journalName=American Journal of Epidemiology, refType=null, unstructuredReference=Brasky TM, Bethea TN, Wesselink AK, et al. Dietary fat intake and risk of uterine leiomyomata: a prospective ultrasound study[J]. American Journal of Epidemiology, 2020, 189(12): 1538-1546., articleTitle=Dietary fat intake and risk of uterine leiomyomata: a prospective ultrasound study, refAbstract=null), Reference(id=1240651453694529792, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2016, volume=18, issue=7, pageStart=2272, pageEnd=2286, url=null, language=null, rfNumber=[5], rfOrder=5, authorNames=Lv LX, Fang DQ, Shi D, journalName=Environmental Microbiology, refType=null, unstructuredReference=Lv LX, Fang DQ, Shi D, et al. Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis[J]. Environmental Microbiology, 2016, 18(7): 2272-2286., articleTitle=Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis, refAbstract=null), Reference(id=1240651453803581704, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2021, volume=11, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[6], rfOrder=6, authorNames=Chen YW, Zhou JH, Wang L, journalName=Frontiers in Cellular and Infection Microbiology, refType=null, unstructuredReference=Chen YW, Zhou JH, Wang L. Role and mechanism of gut microbiota in human disease[J]. Frontiers in Cellular and Infection Microbiology, 2021, 11: 625913., articleTitle=Role and mechanism of gut microbiota in human disease, refAbstract=null), Reference(id=1240651454034268431, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2023, volume=30, issue=12, pageStart=3443, pageEnd=3455, url=null, language=null, rfNumber=[7], rfOrder=7, authorNames=K VK, Bhat RG, Rao BK, journalName=Reproductive Sciences, refType=null, unstructuredReference=K VK, Bhat RG, Rao BK, et al. The gut microbiota: a novel player in the pathogenesis of uterine fibroids[J]. Reproductive Sciences, 2023, 30(12): 3443-3455., articleTitle=The gut microbiota: a novel player in the pathogenesis of uterine fibroids, refAbstract=null), Reference(id=1240651454206234896, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=22, issue=8, pageStart=978, pageEnd=987, url=null, language=null, rfNumber=[8], rfOrder=8, authorNames=刘明, 高亚, 杨珂璐, journalName=中国循证医学杂志, refType=null, unstructuredReference=刘明，高亚，杨珂璐，等．孟德尔随机化研究的报告规范(STROBE-MR)解读[J]．中国循证医学杂志，2022，22（8）：978-987．, articleTitle=孟德尔随机化研究的报告规范(STROBE-MR)解读, refAbstract=null), Reference(id=1240651454319481118, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=22, issue=8, pageStart=978, pageEnd=987, url=null, language=null, rfNumber=[8], rfOrder=9, authorNames=Liu M, Gao Y, Yang KL, journalName=Chinese Journal of Evidence-Based Medicine, refType=null, unstructuredReference=Liu M, Gao Y, Yang KL, et al. Interpretation of STROBE-MR:a statement for strengthening the reporting of observational studies in epidemiology using Mendelian randomization[J]. Chinese Journal of Evidence-Based Medicine, 2022, 22(8): 978-987., articleTitle=Interpretation of STROBE-MR:a statement for strengthening the reporting of observational studies in epidemiology using Mendelian randomization, refAbstract=null), Reference(id=1240651454411755810, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2017, volume=4, issue=4, pageStart=330, pageEnd=345, url=null, language=null, rfNumber=[9], rfOrder=10, authorNames=Zheng J, Baird D, Borges MC, journalName=Current Epidemiology Reports, refType=null, unstructuredReference=Zheng J, Baird D, Borges MC, et al. Recent developments in Mendelian randomization studies[J]. Current Epidemiology Reports, 2017, 4(4): 330-345., articleTitle=Recent developments in Mendelian randomization studies, refAbstract=null), Reference(id=1240651454541779247, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=54, issue=2, pageStart=143, pageEnd=151, url=null, language=null, rfNumber=[10], rfOrder=11, authorNames=Lopera-Maya EA, Kurilshikov A, Van der Graaf A, journalName=Nature Genetics, refType=null, unstructuredReference=Lopera-Maya EA, Kurilshikov A, Van der Graaf A, et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project[J]. Nature Genetics, 2022, 54(2): 143-151., articleTitle=Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project, refAbstract=null), Reference(id=1240651454663414068, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2019, volume=51, issue=4, pageStart=600, pageEnd=605, url=null, language=null, rfNumber=[11], rfOrder=12, authorNames=Sanna SRA, Van zuydam NR, Mahajan A, journalName=Nature Genetics, refType=null, unstructuredReference=Sanna SRA, Van zuydam NR, Mahajan A, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases[J]. Nature Genetics, 2019, 51(4): 600-605., articleTitle=Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases, refAbstract=null), Reference(id=1240651454772465982, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2017, volume=13, issue=11, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=13, authorNames=Hemani G, Tilling K, Davey Smith G, journalName=PLOS Genetics, refType=null, unstructuredReference=Hemani G, Tilling K, Davey Smith G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data[J]. PLOS Genetics, 2017, 13(11): e1007081., articleTitle=Orienting the causal relationship between imprecisely measured traits using GWAS summary data, refAbstract=null), Reference(id=1240651454873129289, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2023, volume=14, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[13], rfOrder=14, authorNames=Qu YM, Chen LL, Guo SJ, journalName=Frontiers in Endocrinology, refType=null, unstructuredReference=Qu YM, Chen LL, Guo SJ, et al. Genetic liability to multiple factors and uterine leiomyoma risk: a Mendelian randomization study[J]. Frontiers in Endocrinology, 2023, 14: 1133260., articleTitle=Genetic liability to multiple factors and uterine leiomyoma risk: a Mendelian randomization study, refAbstract=null), Reference(id=1240651455003152719, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=45, issue=4, pageStart=715, pageEnd=721, url=null, language=null, rfNumber=[14], rfOrder=15, authorNames=Chen YQ, Xiong NL, Xiao JX, journalName=Hypertension Research, refType=null, unstructuredReference=Chen YQ, Xiong NL, Xiao JX, et al. Association of uterine fibroids with increased blood pressure: a cross-sectional study and meta-analysis[J]. Hypertension Research, 2022, 45(4): 715-721., articleTitle=Association of uterine fibroids with increased blood pressure: a cross-sectional study and meta-analysis, refAbstract=null), Reference(id=1240651455087038808, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2016, volume=40, issue=4, pageStart=304, pageEnd=314, url=null, language=null, rfNumber=[15], rfOrder=16, authorNames=Bowden J, Davey smith G, Haycock PC, journalName=Genetic Epidemiology, refType=null, unstructuredReference=Bowden J, Davey smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with Some invalid instruments using a weighted median estimator[J]. Genetic Epidemiology, 2016, 40(4): 304-314., articleTitle=Consistent estimation in Mendelian randomization with Some invalid instruments using a weighted median estimator, refAbstract=null), Reference(id=1240651455187702112, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2003, volume=100, issue=16, pageStart=9440, pageEnd=9445, url=null, language=null, rfNumber=[16], rfOrder=17, authorNames=Storey JD, Tibshirani R, journalName=Proceedings of theNational Academy of Sciences of the United States of America, refType=null, unstructuredReference=Storey JD, Tibshirani R. Statistical significance for genomewide studies[J]. Proceedings of theNational Academy of Sciences of the United States of America, 2003, 100(16): 9440-9445., articleTitle=Statistical significance for genomewide studies, refAbstract=null), Reference(id=1240651456714428776, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2017, volume=474, issue=11, pageStart=1823, pageEnd=1836, url=null, language=null, rfNumber=[17], rfOrder=18, authorNames=Thursby E, Juge N, journalName=Biochemical Journal, refType=null, unstructuredReference=Thursby E, Juge N. Introduction to the human gut microbiota[J]. Biochemical Journal, 2017, 474(11): 1823-1836., articleTitle=Introduction to the human gut microbiota, refAbstract=null), Reference(id=1240651456840257905, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2021, volume=12, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[18], rfOrder=19, authorNames=He S, Li H, Yu ZH, journalName=Frontiers in Microbiology, refType=null, unstructuredReference=He S, Li H, Yu ZH, et al. The gut microbiome and sex Hormone-Related diseases[J]. Frontiers in Microbiology, 2021, 12: 711137., articleTitle=The gut microbiome and sex Hormone-Related diseases, refAbstract=null), Reference(id=1240651456945115510, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2016, volume=83, issue=6, pageStart=645, pageEnd=649, url=null, language=null, rfNumber=[19], rfOrder=20, authorNames=Breban M, journalName=Joint Bone Spine, refType=null, unstructuredReference=Breban M. Gut microbiota and inflammatory joint diseases[J]. Joint Bone Spine, 2016, 83(6): 645-649., articleTitle=Gut microbiota and inflammatory joint diseases, refAbstract=null), Reference(id=1240651457033195903, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2020, volume=20, issue=1, pageStart=98, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=21, authorNames=Wang WT, Li YB, Wu QJ, journalName=BMC Microbiology, refType=null, unstructuredReference=Wang WT, Li YB, Wu QJ, et al. High-throughput sequencing study of the effect of transabdominal hysterectomy on intestinal flora in patients with uterine fibroids[J]. BMC Microbiology, 2020, 20(1): 98., articleTitle=High-throughput sequencing study of the effect of transabdominal hysterectomy on intestinal flora in patients with uterine fibroids, refAbstract=null), Reference(id=1240651457138053514, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2013, volume=369, issue=14, pageStart=1344, pageEnd=1355, url=null, language=null, rfNumber=[21], rfOrder=22, authorNames=Bulun SE, journalName=New England Journal of Medicine, refType=null, unstructuredReference=Bulun SE. Uterine fibroids[J]. New England Journal of Medicine, 2013, 369(14): 1344-1355., articleTitle=Uterine fibroids, refAbstract=null), Reference(id=1240651457255494035, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2021, volume=32, issue=8, pageStart=554, pageEnd=565, url=null, language=null, rfNumber=[22], rfOrder=23, authorNames=Graham ME, Herbert WG, Song SD, journalName=Trends in Endocrinology & Metabolism, refType=null, unstructuredReference=Graham ME, Herbert WG, Song SD, et al. Gut and vaginal microbiomes on steroids: implications for women’s health[J]. Trends in Endocrinology & Metabolism, 2021, 32(8): 554-565., articleTitle=Gut and vaginal microbiomes on steroids: implications for women’s health, refAbstract=null), Reference(id=1240651457351963036, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2012, volume=12, issue=Suppl 1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[23], rfOrder=24, authorNames=Uccello M, Malaguarnera G, Basile F, journalName=BMC Surgery, refType=null, unstructuredReference=Uccello M, Malaguarnera G, Basile F, et al. Potential role of probiotics on colorectal cancer prevention[J]. BMC Surgery, 2012, 12 Suppl 1(Suppl 1): S35., articleTitle=Potential role of probiotics on colorectal cancer prevention, refAbstract=null), Reference(id=1240651457511346593, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=12, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[24], rfOrder=25, authorNames=Mao XT, Peng X, Pan Q, journalName=Frontiers in Cellular and Infection Microbiology, refType=null, unstructuredReference=Mao XT, Peng X, Pan Q, et al. Uterine fibroid patients reveal alterations in the gut microbiome[J]. Frontiers in Cellular and Infection Microbiology, 2022, 12: 863594., articleTitle=Uterine fibroid patients reveal alterations in the gut microbiome, refAbstract=null), Reference(id=1240651457616204198, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=40, issue=10, pageStart=155, pageEnd=159, url=null, language=null, rfNumber=[25], rfOrder=26, authorNames=冯艳霞, 刘霞, 乔娜, journalName=四川中医, refType=null, unstructuredReference=冯艳霞，刘霞，乔娜．大黄牡丹汤辅助治疗子宫肌瘤疗效及对肠道菌群和生殖激素的影响[J]．四川中医，2022，40（10）：155-159．, articleTitle=大黄牡丹汤辅助治疗子宫肌瘤疗效及对肠道菌群和生殖激素的影响, refAbstract=null), Reference(id=1240651457725256107, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=40, issue=10, pageStart=155, pageEnd=159, url=null, language=null, rfNumber=[25], rfOrder=27, authorNames=Feng YX, Liu X, Qiao N, journalName=Journal ofSichuan Traditional Chinese Medicine, refType=null, unstructuredReference=Feng YX, Liu X, Qiao N. Efficacy of using Dahuang Mudan decoction in the adjuvant treatment of uterine leiomyoma and its influence on intestinal flora and reproductive hormones[J]. Journal ofSichuan Traditional Chinese Medicine, 2022, 40(10): 155-159., articleTitle=Efficacy of using Dahuang Mudan decoction in the adjuvant treatment of uterine leiomyoma and its influence on intestinal flora and reproductive hormones, refAbstract=null), Reference(id=1240651457846890934, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2021, volume=16, issue=12, pageStart=1890, pageEnd=1894, url=null, language=null, rfNumber=[26], rfOrder=28, authorNames=张鸢, 吉贞料, journalName=世界中医药, refType=null, unstructuredReference=张鸢，吉贞料．基于肠道菌群稳态探讨大黄牡丹汤治疗子宫肌瘤的作用机制[J]．世界中医药，2021，16（12）：1890-1894．, articleTitle=基于肠道菌群稳态探讨大黄牡丹汤治疗子宫肌瘤的作用机制, refAbstract=null), Reference(id=1240651457960137148, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2021, volume=16, issue=12, pageStart=1890, pageEnd=1894, url=null, language=null, rfNumber=[26], rfOrder=29, authorNames=Zhang Y, Ji ZL, journalName=World Chinese Medicine, refType=null, unstructuredReference=Zhang Y, Ji ZL. Study on the mechanism of Dahuang Mudan decoction in the treatment of uterine leiomyoma based on the effect of intestinal flora on reproductive hormones[J]. World Chinese Medicine, 2021, 16(12): 1890-1894., articleTitle=Study on the mechanism of Dahuang Mudan decoction in the treatment of uterine leiomyoma based on the effect of intestinal flora on reproductive hormones, refAbstract=null), Reference(id=1240651458077577665, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=1, pageStart=1, pageEnd=20, url=null, language=null, rfNumber=[27], rfOrder=30, authorNames=Zafar H, Saier MHJ, journalName=Gut Microbes, refType=null, unstructuredReference=Zafar H, Saier MHJ. Gut bacteroides species in health and disease[J]. Gut Microbes, 2021, 13(1): 1-20., articleTitle=Gut bacteroides species in health and disease, refAbstract=null), Reference(id=1240651458157269450, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2019, volume=46, issue=1, pageStart=55, pageEnd=57, url=null, language=null, rfNumber=[28], rfOrder=31, authorNames=张亚芳, 吴青京, 王青慧, journalName=肿, refType=null, unstructuredReference=张亚芳，吴青京，王青慧，等．肠道菌群与子宫肌瘤的相关性分析[J]．肿，2019，46（1）：55-57．, articleTitle=肠道菌群与子宫肌瘤的相关性分析, refAbstract=null), Reference(id=1240651458274709965, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2019, volume=46, issue=1, pageStart=55, pageEnd=57, url=null, language=null, rfNumber=[28], rfOrder=32, authorNames=Zhang YF, Wu QJ, Wang QH, journalName=Cancer Research on Prevention and Treatment, refType=null, unstructuredReference=Zhang YF, Wu QJ, Wang QH, et al. Relationship between intestinal microflora and uterine myoma[J]. Cancer Research on Prevention and Treatment, 2019, 46(1): 55-57., articleTitle=Relationship between intestinal microflora and uterine myoma, refAbstract=null), Reference(id=1240651458358596050, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, doi=null, pmid=null, pmcid=null, year=2022, volume=2022, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[29], rfOrder=33, authorNames=Qiu JR, Yang MY, Ma YL, journalName=Evidence-based Complementary and Alternative Medicine: eCAM, refType=null, unstructuredReference=Qiu JR, Yang MY, Ma YL, et al. Effect of Ejiao (asini corii colla) and turtle carapace glue on gut microbiota in nude mice with uterine fibroids based on High-Throughput sequencing of 16SrRNA gene[J]. Evidence-based Complementary and Alternative Medicine: eCAM, 2022, 2022: 3934877., articleTitle=Effect of Ejiao (asini corii colla) and turtle carapace glue on gut microbiota in nude mice with uterine fibroids based on High-Throughput sequencing of 16SrRNA gene, refAbstract=null)], funds=[Fund(id=1240651452843086007, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, awardId=首发2018-4-4204, language=CN, fundingSource=首都卫生发展科研专项项目(首发2018-4-4204), fundOrder=null, country=null), Fund(id=1240651452931166403, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, awardId=QN-2020-18, language=CN, fundingSource=北京市中医药科技发展资金项目(QN-2020-18), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240651445960233761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, xref=1., ext=[AuthorCompanyExt(id=1240651445968622369, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China), AuthorCompanyExt(id=1240651445972816674, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651445960233761, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.北京中医药大学东方医院妇科，北京 100078)]), AuthorCompany(id=1240651446094451505, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, xref=2., ext=[AuthorCompanyExt(id=1240651446102840112, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, companyId=1240651446094451505, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.北京中医药大学研究生院)])], figs=[ArticleFig(id=1240651450322309193, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, label=Fig.1, caption=“Leave-one-out” analysis of gut microbiota and uterine fibroids, figureFileSmall=V08XhKR/gB0fhpTxT5+PcA==, figureFileBig=TJ9vx9bgJesOfDknZXPQrA==, tableContent=null), ArticleFig(id=1240651450431361105, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, label=图1, caption=肠道菌群与子宫肌瘤的“留一法”分析

注：A、B、C、D、E、F分别为肠道拟杆菌、罗氏菌属、乳杆菌目、链状双歧杆菌、瘤胃球菌科、厚壁菌与子宫肌瘤的“留一法”图。

, figureFileSmall=V08XhKR/gB0fhpTxT5+PcA==, figureFileBig=TJ9vx9bgJesOfDknZXPQrA==, tableContent=null), ArticleFig(id=1240651450666242155, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, label=Fig.2, caption=Funnel plot analysis of gut microbiota and uterine fibroids, figureFileSmall=q00QWvrCevp2b5h8vaj0iw==, figureFileBig=ohYU0hL+4F0jKTTbta0xIw==, tableContent=null), ArticleFig(id=1240651450775294069, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, label=图2, caption=肠道菌群与子宫肌瘤的漏斗图分析

注：A、B、C、D、E、F分别为肠道拟杆菌、罗氏菌属、乳杆菌目、链状双歧杆菌、瘤胃球菌科、厚壁菌与子宫肌瘤的漏斗图。

, figureFileSmall=q00QWvrCevp2b5h8vaj0iw==, figureFileBig=ohYU0hL+4F0jKTTbta0xIw==, tableContent=null), ArticleFig(id=1240651452264271998, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, label=Table 1, caption=

Results of MR Analysis of gut microbiota and uterine fibroids

, figureFileSmall=null, figureFileBig=null, tableContent=
菌属SNP（个）方法βSEOR（95%CI）PPFDR
肠道拟杆菌GCST900278228IVW0.0430.0191.045（1.006~1.085）0.0230.669
MR Egger0.0950.0851.100（0.930~1.299）0.308
WME0.0520.0251.053（1.002~1.107）0.040
罗氏菌属GCST9002771314IVW0.0720.0341.074（1.004~1.149）0.0370.698
MR Egger0.0860.1441.157（0.938~1.427）0.564
WME0.0710.0431.092（1.021~1.167）0.098
乳杆菌目GCST9002773911IVW0.0640.0241.066（1.017~1.118）0.0080.067
MR Egger0.1460.1070.908（0.470-1.755）0.206
WME0.0880.0340.918（0.785~1.074）0.011
链状双歧杆菌GCST900277566IVW-0.0490.0170.952（0.921~0.985）0.0040.030
MR Egger-0.1170.0820.890（0.758~1.044）0.226
WME-0.0550.0210.946（0.907~0.987）0.010
瘤胃球菌科GCST900276767IVW0.1120.0441.119（1.027~1.219）0.0100.519
MR Egger0.0670.1631.070（0.777~1.473）0.696
WME0.1320.0561.142（1.023~1.274）0.018
厚壁菌GCST9002765313IVW0.0500.0241.052（1.003~1.102）0.0350.669
MR Egger0.0860.0951.090（0.904~1.313）0.385
WME0.0680.0331.071（1.005~1.142）0.036
), ArticleFig(id=1240651452394295432, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, label=表1, caption=

肠道菌群与子宫肌瘤的MR分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
菌属SNP（个）方法βSEOR（95%CI）PPFDR
肠道拟杆菌GCST900278228IVW0.0430.0191.045（1.006~1.085）0.0230.669
MR Egger0.0950.0851.100（0.930~1.299）0.308
WME0.0520.0251.053（1.002~1.107）0.040
罗氏菌属GCST9002771314IVW0.0720.0341.074（1.004~1.149）0.0370.698
MR Egger0.0860.1441.157（0.938~1.427）0.564
WME0.0710.0431.092（1.021~1.167）0.098
乳杆菌目GCST9002773911IVW0.0640.0241.066（1.017~1.118）0.0080.067
MR Egger0.1460.1070.908（0.470-1.755）0.206
WME0.0880.0340.918（0.785~1.074）0.011
链状双歧杆菌GCST900277566IVW-0.0490.0170.952（0.921~0.985）0.0040.030
MR Egger-0.1170.0820.890（0.758~1.044）0.226
WME-0.0550.0210.946（0.907~0.987）0.010
瘤胃球菌科GCST900276767IVW0.1120.0441.119（1.027~1.219）0.0100.519
MR Egger0.0670.1631.070（0.777~1.473）0.696
WME0.1320.0561.142（1.023~1.274）0.018
厚壁菌GCST9002765313IVW0.0500.0241.052（1.003~1.102）0.0350.669
MR Egger0.0860.0951.090（0.904~1.313）0.385
WME0.0680.0331.071（1.005~1.142）0.036
), ArticleFig(id=1240651452549484698, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=EN, label=Table 2, caption=

Results of sensitivity analysis of gut microbiota and uterine fibroids

, figureFileSmall=null, figureFileBig=null, tableContent=
菌群方法Cochran Q异质性检验MR-Egger intercept多效性检验
Q值P值截距值P值
肠道拟杆菌GCST90027822IVW5.7620.568-0.0110.599
罗氏菌属GCST90027713IVW18.0540.155-0.0010.922
乳杆菌目GCST90027739IVW9.4940.486-0.0120.453
链状双歧杆菌GCST90027756IVW1.8860.8650.0210.443
瘤胃球菌科GCST90027676IVW1.5010.9590.0050.786
厚壁菌GCST90027653IVW12.2270.428-0.0050.704
), ArticleFig(id=1240651452671119528, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240651442298606214, language=CN, label=表2, caption=

肠道菌群与子宫肌瘤的敏感性分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
菌群方法Cochran Q异质性检验MR-Egger intercept多效性检验
Q值P值截距值P值
肠道拟杆菌GCST90027822IVW5.7620.568-0.0110.599
罗氏菌属GCST90027713IVW18.0540.155-0.0010.922
乳杆菌目GCST90027739IVW9.4940.486-0.0120.453
链状双歧杆菌GCST90027756IVW1.8860.8650.0210.443
瘤胃球菌科GCST90027676IVW1.5010.9590.0050.786
厚壁菌GCST90027653IVW12.2270.428-0.0050.704
)], attaches=null, journal=Journal(id=1227664546253402114, delFlag=0, nameCn=现代预防医学, nameEn=Modern Preventive Medicine, nameHistory1=null, nameHistory2=null, issn=1003-8507, eissn=null, cn=51-1365/R, coden=null, periodic=3, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=IeiuPXEZi6AA+k0VfvoiOQ==, journalPrice=null, startedYear=null, abbrevIsoEn=Modern Preventive Medicine, journalRemark=null, publicationField=null, createdTime=1770627636734, updatedTime=1770628902248, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=M, firstLetterEn=M, subjectCode=Life Sciences, subjectName=null, subjectCodeEn=Life Sciences, subjectNameEn=null, picCn=IeiuPXEZi6AA+k0VfvoiOQ==, picEn=/9iTl8/ndms4tBz1fL28Pg==, jcr=null, cjcr=null, exts=[JournalExt(id=1227669854342280188, language=CN, name=现代预防医学, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1770628902278, updatedTime=1770628902278, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=http://xdyfyxzz.paperopen.com/#/regist, submissionEditorUrl=http://xdyfyxzz.paperopen.com/#/Login, submissionReviewUrl=http://xdyfyxzz.paperopen.com/#/Login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1227669854396806141, language=EN, name=Modern Preventive Medicine, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1770628902291, updatedTime=1770628902291, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=http://xdyfyxzz.paperopen.com/#/regist, submissionEditorUrl=http://xdyfyxzz.paperopen.com/#/Login, submissionReviewUrl=http://xdyfyxzz.paperopen.com/#/Login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1227665162245664772, websiteList=[Website(id=1227687234141352800, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1227665162245664772, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/xdyfyx/CN, language=CN, createTime=1770633045945, createBy=18614031015, updateTime=1770633090526, updateBy=18614031015, name=现代预防医学-中文, tplId=1146099689490845704, title=现代预防医学, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1227687735088051072, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=articleTextType, value=kx, createTime=1770633165380, updateTime=1770633165380, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735071273853, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=banner, value=null, createTime=1770633165376, updateTime=1770633165376, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735113216899, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=grayFlag, value=0, createTime=1770633165386, updateTime=1770633165386, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735062885244, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=logo, value=https://castjournals.cast.org.cn/joweb/xdyfyx/CN/file/pic?fileId=/XB5plC0xuykmQnycvtyrw==, createTime=1770633165374, updateTime=1770633165374, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735125799813, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=minRunFlag, value=0, createTime=1770633165389, updateTime=1770633165389, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735083856767, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/xdyfyx/CN/file/pic, createTime=1770633165379, updateTime=1770633165379, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735121605508, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=silenceFlag, value=0, createTime=1770633165388, updateTime=1770633165388, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735079662462, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1770633165378, updateTime=1770633165378, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735096439681, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=themeColor, value=null, createTime=1770633165382, updateTime=1770633165382, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687735104828290, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234141352800, code=themeStyle, value=null, createTime=1770633165384, updateTime=1770633165384, creator=18614031015, updator=18614031015)]), Website(id=1227687234338485094, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1227665162245664772, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/xdyfyx/EN, language=EN, createTime=1770633045992, createBy=18614031015, updateTime=1770633115374, updateBy=18614031015, name=现代预防医学-英文, tplId=1146101810881728533, title=Modern Preventive Medicine, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1227687709129507332, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=articleTextType, value=kx, createTime=1770633159191, updateTime=1770633159191, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709108535809, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=banner, value=null, createTime=1770633159186, updateTime=1770633159186, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709167256071, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=grayFlag, value=0, createTime=1770633159200, updateTime=1770633159200, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709095952896, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=logo, value=https://castjournals.cast.org.cn/joweb/xdyfyx/EN/file/pic?fileId=/XB5plC0xuykmQnycvtyrw==, createTime=1770633159183, updateTime=1770633159183, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709179838985, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=minRunFlag, value=0, createTime=1770633159203, updateTime=1770633159203, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709121118723, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/xdyfyx/EN/file/pic, createTime=1770633159189, updateTime=1770633159189, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709171450376, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=silenceFlag, value=0, createTime=1770633159201, updateTime=1770633159201, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709112730114, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1770633159187, updateTime=1770633159187, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709133701637, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=themeColor, value=null, createTime=1770633159192, updateTime=1770633159192, creator=18614031015, updator=18614031015), WebsiteProps(id=1227687709154673158, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1227687234338485094, code=themeStyle, value=null, createTime=1770633159197, updateTime=1770633159197, creator=18614031015, updator=18614031015)])], journalTitle=现代预防医学, weixinUrl=null, journalUrl=http://xdyfyxzz.paperopen.com/, iacademicId=null, status=1, seqNo=null, journalTitleEn=Modern Preventive Medicine, journalPhotoCn=IeiuPXEZi6AA+k0VfvoiOQ==, journalPhotoEn=/9iTl8/ndms4tBz1fL28Pg==, journalFirstLetter=M, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false), detailUrlCn=https://castjournals.cast.org.cn/joweb/xdyfyx/CN/10.20043/j.cnki.MPM.202403026, detailUrlEn=https://castjournals.cast.org.cn/joweb/xdyfyx/EN/10.20043/j.cnki.MPM.202403026, pdfUrlCn=https://castjournals.cast.org.cn/joweb/xdyfyx/CN/PDF/10.20043/j.cnki.MPM.202403026, pdfUrlEn=https://castjournals.cast.org.cn/joweb/xdyfyx/EN/PDF/10.20043/j.cnki.MPM.202403026, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, reference=null)
收藏切换
肠道菌群与子宫肌瘤因果关系的孟德尔随机化研究
收藏切换
PDF下载
梁伟 1 , 卢英 1 , 张晓晓 2 , 贡欣 1
现代预防医学 | 流行病与统计方法 2024,51(12): 2140-2145
收起
收藏切换
现代预防医学 | 流行病与统计方法 2024, 51(12): 2140-2145
肠道菌群与子宫肌瘤因果关系的孟德尔随机化研究
全屏
梁伟1, 卢英1, 张晓晓2, 贡欣1
作者信息
  • 1.北京中医药大学东方医院妇科，北京 100078
  • 2.北京中医药大学研究生院

    • 梁伟（1999—），女，硕士在读，研究方向：中西医结合防治生殖内分泌疾病

通讯作者:

贡欣，E-mail：
Causal relationship between gut microbiota and uterine fibroids: a Mendelian randomization study
Wei LIANG1, Ying LU1, Xiao-xiao ZHANG2, Xin GONG1
Affiliations
  • Department of Gynecology, Dong Fang hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China
出版时间: 2024-06-25 doi: 10.20043/j.cnki.MPM.202403026
文章导航
收藏切换
摘要
收起
目的

采用孟德尔随机化方法来评估肠道菌群与子宫肌瘤风险之间的潜在因果关系。

方法

使用2022年荷兰微生物项目组发布的肠道菌群全基因组关联研究（GWAS）统计数据（n=7 738例）和芬兰R9数据库中子宫肌瘤的GWAS数据（31 661例子宫肌瘤患者和179 209例对照）。采用逆方差加权法（IVW）、MR-Egger回归法、加权中位数法来研究肠道菌群与子宫肌瘤之间的因果关系。敏感性分析用于检验孟德尔随机化分析结果是否可靠。

结果

IVW的结果显示肠道拟杆菌（OR=1.045，95%CI：1.006~1.085）、瘤胃球菌科（OR=1.119，95%CI：1.027~1.219）、罗氏菌属（OR=1.074，95%CI：1.004~1.149）、乳杆菌目（OR=1.066，95%CI：1.017~1.118）和厚壁菌（OR=1.052，95%CI：1.003~1.102）与子宫肌瘤的发病呈正相关，经FDR矫正后P>0.05，并未发现显著的统计学差异。而链状双歧杆菌（OR=0.952，95%CI：0.921~0.985）与子宫肌瘤的发病呈负相关，经FDR校正后P<0.05，表明二者之间的因果关联具有统计学意义。敏感性分析均未发现存在显著异质性和水平多效性。

结论

链状双歧杆菌可能是子宫肌瘤发病的保护因素，肠道拟杆菌、瘤胃球菌科、罗氏菌属、乳杆菌目和厚壁菌可能是子宫肌瘤发病的潜在危险因素，但有待更多研究进行验证。本研究提供了可进一步研究的菌群信息，这有望改善子宫肌瘤的发病与预后。

子宫肌瘤  /  肠道菌群  /  孟德尔随机化  /  全基因组关联研究  /  因果关系
Objective

To assess the potential causal relationship between gut microbiota and the risk of uterine fibroids using a Mendelian randomization approach.

Methods

We used the genome-wide association study (GWAS) statistics of gut microbiota published by the Netherlands Microbiome Project in 2022 (n=7 738) and the GWAS data of uterine fibroids from the Finnish R9 database (31 661 uterine fibroid patients and 179 209 controls). Inverse variance weighting (IVW), MR-Egger regression and weighted median method were used to study the causal relationship between intestinal flora and uterine fibroids. Sensitivity analyses were performed to test the reliability of the results of the Mendelian randomization analysis.

Results

IVW results showed that Bacteroides (OR=1.045, 95%CI: 1.006-1.085), Ruminococcaceae (OR=1.119, 95%CI: 1.027-1.219), Roseobacter(OR=1.074, 95%CI: 1.004-1.149), Lactobacillus (OR=1.066, 95%CI: 1.017-1.118) and Firmicutes (OR=1.052, 95%CI: 1.003-1.102) were positively correlated with the incidence of uterine fibroids. No significant statistical difference was foundafter FDR correction (P>0.05).Bifidobacterium was negatively correlated with the incidence of uterine fibroids (OR=0.952,95%CI: 0.921-0.985). The causal association was statistically significant after FDR correction (P<0.05). No significant heterogeneity and horizontal pleiotropy were found in the sensitivity analysis.

Conclusion

Bifidobacterium may be a protective factor for the pathogenesis of uterine fibroids, while Bacteroides, Ruminococcaceae, Roseobacter, Lactobacillus and Firmicutes may be a potential risk factor for the pathogenesis of uterine fibroids. However, more studies are needed to verify the results. This study provides information about the microbiota that can be further studied, which is expected to improve the incidence and prognosis of uterine fibroids.

Uterine fibroids  /  Gut microbiota  /  Mendelian randomization  /  Genome-wide association study  /  Causal relationship
梁伟, 卢英, 张晓晓, 贡欣. 肠道菌群与子宫肌瘤因果关系的孟德尔随机化研究. 现代预防医学, 2024 , 51 (12) : 2140 -2145 . DOI: 10.20043/j.cnki.MPM.202403026
Wei LIANG, Ying LU, Xiao-xiao ZHANG, Xin GONG. Causal relationship between gut microbiota and uterine fibroids: a Mendelian randomization study[J]. Modern Preventive Medicine, 2024 , 51 (12) : 2140 -2145 . DOI: 10.20043/j.cnki.MPM.202403026
正文
收起
子宫肌瘤是女性最常见的盆腔肿瘤之一，通常表现为异常子宫出血、盆腔压迫感或者疼痛等，严重者可能影响女性生殖能力，包括不孕、产科并发症和流产等不良结局[1]。流行病学统计显示，30～50岁育龄期女性发病率高达25%以上，且随着年龄增长而增加[2-3]。子宫肌瘤已知的危险因素包括遗传、激素、饮食习惯、肥胖和胃肠道疾病等[4]。
肠道菌群是由寄居在人体肠道内大量细菌构成的微生物群落，时刻影响着机体免疫功能，对人体激素合成与分泌、微量元素等影响深远。近年来，人体肠道菌群失调逐渐被证实与肿瘤、消化、代谢性疾病等在内的50多种疾病相关[5-6]。观察性研究发现，子宫肌瘤的生长和持续存在取决于体内雌激素、孕酮的水平，而雌激素的合成及分泌与肠道菌群的菌种和数量存在相关性[7]。然而，观察性研究会受到混杂因素和反向因果的干扰，存在一定偏倚，故两者的因果关系尚有待明确。
孟德尔随机化（Mendelian randomization，MR）是一种利用单核苷酸多态性（Single nucleotide polymorphism，SNP）作为工具变量来推断暴露表型与结局疾病之间因果关系的方法。MR分析中等位基因随机分配，在不受外部环境因素影响的情况下实现类似的随机化效应，故可以规避其他混杂因素和反向因果关联造成的偏差，从而提高研究的准确性和置信度[8-9]。目前，尚未有关于肠道菌群与子宫肌瘤因果关系的MR研究。因此，本研究采用MR的方法，探索肠道菌群与子宫肌瘤之间的因果关系，以期为子宫肌瘤的预防和治疗提供新的思路。
1　研究资料与方法
收起
1.1　研究设计
本研究将肠道菌群作为暴露因素，子宫肌瘤作为结局变量。利用两样本MR的方法进行因果分析，为了获得可靠的结果，需要满足MR的3个关键假设：（1）相关性假设：最终纳入的工具变量，即SNP与暴露（肠道菌群）密切相关；（2）独立性假设：SNP独立于已知的混杂因素；（3）排他性假设：SNP不能直接影响结局，只能通过与暴露（肠道菌群）的关联间接影响结局（子宫肌瘤）。
1.2　数据来源
肠道菌群遗传基因数据是来自2022年荷兰微生物项目组发布的一项大型全基因组关联研究（Genome-wide association study，GWAS）统计数据[10]，共有7 738名来自欧洲地区的参与者，涉及207个肠道相关微生物类群，并使用直接分类法进行分类，包括5个门、10个纲、13个目、26个科、48个属和105个种。该研究还发布了205种微生物作用通路，以丰富菌群微生物组成。子宫肌瘤的遗传数据则来自于2023年5月11日发布的芬兰R9数据库（https://r9.finngen.fi/），纳入诊断为子宫纤维肌瘤、子宫壁间肌瘤、子宫浆膜下平滑肌瘤、子宫粘膜下肌瘤及其他类型的子宫平滑肌瘤患者，涉及31 661例子宫肌瘤病例和179 209例对照，均为欧洲血统，总样本量为210 870例，SNP的数量为20 133 639。由于使用的数据都是公开数据库，因此不需要额外的伦理批准。
1.3　工具变量的选择
首先，筛选与特定细菌类群（P<1.0×10-5）密切相关的SNP作为工具变量[11]。基于欧洲基因组样本数据进行连锁不平衡分析，在分析过程中，具有回文结构的SNP被自动删除，运行参数设置为r2<0.001，kb=10 000；同时使用Steiger Test统计量检验MR分析的方向性[12]。其次，使用Phenoscanner排除与子宫肌瘤相关的混杂因素（体重指数、初潮年龄、冠状动脉疾病）[13-14]。最后，通过计算F统计值评估SNP和暴露之间相关性的统计强度，F>10表示存在弱工具变量偏差的可能性小，故剔除F<10的工具变量。F值计算公式如下：F=[（n-k-1）/k]×r2/（1-r2）。r2为SNP解释的暴露方差，n为暴露数据中样本数量，k为SNP的个数。r2的计算公式如下：r2=2×β2×EAF×（1-EAF）/2×β2×EAF×（1-EAF）+SE2×2×N×EAF（1-EAF）。其中，EAF为效应等位基因频率，β为等位基因效应值，SE为标准差。
本研究选择了207种肠道菌群的GWAS数据作为研究暴露，其中包括5个门、10个纲、13个目、26个科、48个属和105个种。并根据设定的筛选标准筛选出符合条件的不同菌种数目的SNP。计算Steiger Test统计量全部通过，说明没有反向因果关系。考虑到混杂因素的影响，进一步使用Phenoscanner排除混杂因素，删除与混杂因素相关的5个SNP。共筛选出8个与肠道拟杆菌相关SNP，14个罗氏菌相关SNP，11个乳杆菌目的SNP，6个链状双歧杆菌的SNP，7个瘤胃球菌科的SNP和13个厚壁菌的SNP。
1.4　两样本MR分析
本研究采用逆方差加权分析（Inversevariance weighted，IVW）为主要方法，其特点是回归分析时不考虑截距项，并且用结局方差的倒数作为权重来进行拟合。MR-Egger回归在存在基因多效性的情况下也能得到一致性的估计。加权中位数法（Weighted median，WME）在超过50%的无效SNP时，仍能提供稳定的因果效应估计[15]。因此，本研究将MR-Egger和WME作为辅助分析方法，当不存在水平多效性时，以IVW分析结果为主，P<0.05表示存在统计学意义的因果关系。根据肠道菌群的分类，并进行对结果错误发现率（False discovery rate，FDR）的分级校正，以推断肠道菌群和子宫肌瘤之间是否存在因果关系。当经FDR校正后的P值<0.05时，认为肠道菌群和子宫肌瘤的关联具有统计学意义[16]。
1.5　敏感性分析
敏感性包括异质性检验、水平多效性检验、“留一法”检验。Cochran Q检验判断MR分析结果的异质性，若P<0.05，则证明分析结果具有显著的异质性。水平多效性通过MR-Egger intercept进行检验，如果MR-Egger分析中存在显著的截距项（P>0.05），则表明存在潜在的水平多效性。此外，进行MR-PRESSO离群值检验，若检测到异常值，则将其移除并将剩余的SNP进行重新分析。采用留一法分析来评估因果关系是否由单个SNP决定以验证结果是否稳健。人体肠道菌群与子宫肌瘤的因果关系以优势比（Odds radio，OR）及其95%置信区间（Confidence interval，CI）表示，如果P<0.05，则为其可能存在因果关系提供证据。
所有统计分析均在RStudio软件（版本4.1.3）中进行，使用两样本MR和MR-PRESSO软件包分析。
2　结果
收起
以IVW方法为筛选结果，共发现6种肠道菌群与子宫肌瘤存在关联，经过FDR校正后，发现链状双歧杆菌（OR=0.952，95%CI：0.921~0.985，P=0.004，PFDR值=0.030）与子宫肌瘤的发病呈负相关，可能是子宫肌瘤发生的保护因素；而肠道拟杆菌、瘤胃球菌科、罗氏菌属、乳杆菌目和厚壁菌与子宫肌瘤的发病呈正相关，PFDR值矫正后，P>0.05，认为以上肠道菌群和子宫肌瘤的关联不具有统计学意义。见表1。
异质性Cochran Q检验结果显示P均大于0.05，表明所选的工具变量之间没有明显的异质性（见表2）。对MR-Egger的截距项进行统计检验，显示所有P值均大于0.05，认为没有水平多效性的存在（见表2）。“留一法”评估MR结果稳定性，发现纳入的SNP的效应值和总效应值大小较为接近，尚未出现明显的离群值（见图1）。漏斗图结果表明当逐个剔除SNP分析时，因果关联效应的散点基本呈对称分布，结果不存在潜在偏倚（见图2）。此外，Steiger Test统计量全部通过，说明没有反向因果关系。
3　讨论
收起
据我们所知，关于肠道微生物群和子宫肌瘤相关性的研究报道较少，亟待较高质量的研究明确二者之间的潜在联系。本研究首次通过MR方法评估肠道菌群与子宫肌瘤之间潜在的因果关系，基于IVW的结果显示肠道拟杆菌、罗氏菌属、瘤胃球菌科、厚壁菌与子宫肌瘤的发病存在正向因果关联。但FDR校正结果显示不存在显著因果关系；而乳杆菌目和链状双歧杆菌与子宫肌瘤的患病风险呈反向因果关联。经FDR校正之后，乳杆菌目为假阳性结果，不支持其对子宫肌瘤有保护作用，而链状双歧杆菌相对丰度的升高与子宫肌瘤的患病风险仍呈负相关。
人体肠道微生物群的组成可通过体内雌激素或其他激素的相互作用而发生变化，进而影响机体平衡，在生殖内分泌系统中起着至关重要的作用[17]。进一步研究发现肠道微生物群可通过其代谢物、免疫系统和慢性炎症之间的相互作用来调节性激素的水平[18]，相反，雌激素水平也可导致肠道菌群中的数量和菌株发生改变。Breban等[19]发现雌激素水平的降低可导致肠道菌群多样性的减少和厚壁细菌丰度的减少。此外，Wang等[20]研究发现当体内雌激素水平下降时，变形菌门和厚壁菌门增多，拟杆菌门减少，故肠道菌群和雌激素水平具有相关性。由于子宫肌瘤是激素依赖性肿瘤，雌激素水平的增加会显著增加患子宫肌瘤的风险[21]。因此，肠道菌群与子宫肌瘤的发生密切相关。
双歧杆菌是人体一种重要的肠道有益菌，对人体健康具有生物屏障、免疫增强和改善胃肠道功能等多种重要的生理功能。既往研究报道双歧杆菌属产生的β-葡萄糖醛酸酶能够与体内雌激素结合，增加水溶性，通过尿液代谢转化为游离形式，从而降低雌激素重吸收率，维持雌激素在生理水平发挥正常的生物学效应，降低雌激素代谢类疾病的患病风险[22-23]。Mao等[24]采用生物信息学分析方法检测肠道微生物群，结果发现与健康对照组相比，子宫肌瘤患者肠道菌群的多样性显著下降，在差异丰度分析上，子宫肌瘤患者的双歧杆菌、柠檬乳杆菌等细菌种类下调，而假单胞菌和羊膜普雷沃菌等细菌种类上调。有学者应用中药大黄牡丹汤辅助治疗子宫肌瘤，发现其可显著提高双歧杆菌和乳酸菌含量，进而调节肠道环境，缩小肌瘤体积[25-26]。这可能与提高白介素-6因子水平，降低肿瘤坏死因子-2α水平，激活NK细胞活性，纠正CD4+/CD8+细胞比值，增加了机体免疫功能有关。我们的研究发现链状双歧杆菌数量的增加可减少子宫肌瘤患病风险，FDR校正后显示链状双歧杆菌可能是子宫肌瘤发病的保护因素，我们考虑双歧杆菌丰度的增加能够使肠道微生物群处于平衡状态，进而维持体内雌激素处于正常水平，因此其与子宫肌瘤发病风险呈现负相关。
拟杆菌是一种重要的肠道基石菌属，其与人体具有共生关系，当拟杆菌进入到除胃肠区域以外的身体部位，可引起或加剧脓肿等感染[27]。张亚芳等[28]发现子宫肌瘤组的拟杆菌和变形菌门的水平显著低于空白对照组，拟杆菌门、变形菌门与子宫肌瘤的发生率呈负相关。Qiu等[29]采用基因测序技术对阿胶和龟甲壳胶等药物干预后大鼠子宫肌瘤的肠道菌群结构进行研究。多样性分析结果表明，给药后肠道菌群的丰度和多样性呈上升趋势，但无显著性差异，这可能与给药时间短有关系。此外，给药4周后大鼠的菌群结构与给药前有显著差异，包括厚壁菌门减少，拟杆菌门和变形菌门增加。进一步分析得出龟甲壳胶可能通过提高雌二醇的水平，降低肿瘤坏死因子-α等炎性因子水平，抑制炎症反应，从而发挥抗子宫肌瘤作用。我们的研究从遗传学角度证实肠道拟杆菌会增加子宫肌瘤的发病风险，但FDR校正结果未显示两者之间存在显著的因果关联，还需进一步验证。
本研究仍存在一定的局限性。首先，纳入研究的数据库均来自于欧洲血统，结论是否适合于亚洲、非洲等其他人种，尚有待进一步验证，以确认结果的普遍性。第二，MR分析方法是一种理论的因果关系分析方法，肠道微生物群与子宫肌瘤之间潜在的生物学机制尚不清楚，还需在人类和动物模型中进行深入的机制探讨。第三，本研究基于荷兰微生物项目组的GWAS数据集，可能缺少其他与子宫肌瘤有因果关系的微生物类群。最后，尽管本研究初步发现了肠道拟杆菌、瘤胃球菌科、罗氏菌属、乳杆菌目和厚壁菌可能是子宫肌瘤发病的潜在因素，但其结果并未通过FDR的校正阈值，考虑存在假阳性风险，后续研究需纳入更大样本的数据库及更多观察性研究进行验证。
本研究发现链状双歧杆菌可能是子宫肌瘤发病的保护因素，肠道拟杆菌、瘤胃球菌科、罗氏菌属、乳杆菌目和厚壁菌可能是子宫肌瘤发病的潜在危险因素，但有待更多研究进行验证。本研究提供了可进一步研究的菌群信息，这有望改善子宫肌瘤的发病与预后。
基金
收起
  • 首都卫生发展科研专项项目(首发2018-4-4204)
  • 北京市中医药科技发展资金项目(QN-2020-18)
文献
收起
参考文献 引证文献
排序方式：
[1]
Stewart EA, Cookson CL, Gandolfo RA, et al. Epidemiology of uterine fibroids: a systematic review[J]. BJOG : an International Journal of Obstetrics and Gynaecology, 2017, 124(10): 1501-1512.
[2]
子宫肌瘤的诊治中国专家共识专家组．子宫肌瘤的诊治中国专家共识[J]．中华妇产科杂志，2017，52（12）：793-800．
Diagnosis and Treatment of Uterine Fibroids Chinese Expert Consensus Expert Group. Chinese expert consensus on the diagnosis and treatment of uterine fibroids[J]. Chinese Journal of Obstetrics and Gynecology, 2017, 52(12): 793-800.
[3]
Wegienka G, Havstad S, Coleman C, et al. Ultrasound-confirmed, age-specific uterine leiomyoma incidence in a cohort of black individuals[J]. Obstetrics and Gynecology, 2022, 140(6): 1042-1048.
[4]
Brasky TM, Bethea TN, Wesselink AK, et al. Dietary fat intake and risk of uterine leiomyomata: a prospective ultrasound study[J]. American Journal of Epidemiology, 2020, 189(12): 1538-1546.
[5]
Lv LX, Fang DQ, Shi D, et al. Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis[J]. Environmental Microbiology, 2016, 18(7): 2272-2286.
[6]
Chen YW, Zhou JH, Wang L. Role and mechanism of gut microbiota in human disease[J]. Frontiers in Cellular and Infection Microbiology, 2021, 11: 625913.
[7]
K VK, Bhat RG, Rao BK, et al. The gut microbiota: a novel player in the pathogenesis of uterine fibroids[J]. Reproductive Sciences, 2023, 30(12): 3443-3455.
[8]
刘明，高亚，杨珂璐，等．孟德尔随机化研究的报告规范(STROBE-MR)解读[J]．中国循证医学杂志，2022，22（8）：978-987．
Liu M, Gao Y, Yang KL, et al. Interpretation of STROBE-MR:a statement for strengthening the reporting of observational studies in epidemiology using Mendelian randomization[J]. Chinese Journal of Evidence-Based Medicine, 2022, 22(8): 978-987.
[9]
Zheng J, Baird D, Borges MC, et al. Recent developments in Mendelian randomization studies[J]. Current Epidemiology Reports, 2017, 4(4): 330-345.
[10]
Lopera-Maya EA, Kurilshikov A, Van der Graaf A, et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project[J]. Nature Genetics, 2022, 54(2): 143-151.
[11]
Sanna SRA, Van zuydam NR, Mahajan A, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases[J]. Nature Genetics, 2019, 51(4): 600-605.
[12]
Hemani G, Tilling K, Davey Smith G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data[J]. PLOS Genetics, 2017, 13(11): e1007081.
[13]
Qu YM, Chen LL, Guo SJ, et al. Genetic liability to multiple factors and uterine leiomyoma risk: a Mendelian randomization study[J]. Frontiers in Endocrinology, 2023, 14: 1133260.
[14]
Chen YQ, Xiong NL, Xiao JX, et al. Association of uterine fibroids with increased blood pressure: a cross-sectional study and meta-analysis[J]. Hypertension Research, 2022, 45(4): 715-721.
[15]
Bowden J, Davey smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with Some invalid instruments using a weighted median estimator[J]. Genetic Epidemiology, 2016, 40(4): 304-314.
[16]
Storey JD, Tibshirani R. Statistical significance for genomewide studies[J]. Proceedings of theNational Academy of Sciences of the United States of America, 2003, 100(16): 9440-9445.
[17]
Thursby E, Juge N. Introduction to the human gut microbiota[J]. Biochemical Journal, 2017, 474(11): 1823-1836.
[18]
He S, Li H, Yu ZH, et al. The gut microbiome and sex Hormone-Related diseases[J]. Frontiers in Microbiology, 2021, 12: 711137.
[19]
Breban M. Gut microbiota and inflammatory joint diseases[J]. Joint Bone Spine, 2016, 83(6): 645-649.
[20]
Wang WT, Li YB, Wu QJ, et al. High-throughput sequencing study of the effect of transabdominal hysterectomy on intestinal flora in patients with uterine fibroids[J]. BMC Microbiology, 2020, 20(1): 98.
[21]
Bulun SE. Uterine fibroids[J]. New England Journal of Medicine, 2013, 369(14): 1344-1355.
[22]
Graham ME, Herbert WG, Song SD, et al. Gut and vaginal microbiomes on steroids: implications for women’s health[J]. Trends in Endocrinology & Metabolism, 2021, 32(8): 554-565.
[23]
Uccello M, Malaguarnera G, Basile F, et al. Potential role of probiotics on colorectal cancer prevention[J]. BMC Surgery, 2012, 12 Suppl 1(Suppl 1): S35.
[24]
Mao XT, Peng X, Pan Q, et al. Uterine fibroid patients reveal alterations in the gut microbiome[J]. Frontiers in Cellular and Infection Microbiology, 2022, 12: 863594.
[25]
冯艳霞，刘霞，乔娜．大黄牡丹汤辅助治疗子宫肌瘤疗效及对肠道菌群和生殖激素的影响[J]．四川中医，2022，40（10）：155-159．
Feng YX, Liu X, Qiao N. Efficacy of using Dahuang Mudan decoction in the adjuvant treatment of uterine leiomyoma and its influence on intestinal flora and reproductive hormones[J]. Journal ofSichuan Traditional Chinese Medicine, 2022, 40(10): 155-159.
[26]
张鸢，吉贞料．基于肠道菌群稳态探讨大黄牡丹汤治疗子宫肌瘤的作用机制[J]．世界中医药，2021，16（12）：1890-1894．
Zhang Y, Ji ZL. Study on the mechanism of Dahuang Mudan decoction in the treatment of uterine leiomyoma based on the effect of intestinal flora on reproductive hormones[J]. World Chinese Medicine, 2021, 16(12): 1890-1894.
[27]
Zafar H, Saier MHJ. Gut bacteroides species in health and disease[J]. Gut Microbes, 2021, 13(1): 1-20.
[28]
张亚芳，吴青京，王青慧，等．肠道菌群与子宫肌瘤的相关性分析[J]．肿，2019，46（1）：55-57．
Zhang YF, Wu QJ, Wang QH, et al. Relationship between intestinal microflora and uterine myoma[J]. Cancer Research on Prevention and Treatment, 2019, 46(1): 55-57.
[29]
Qiu JR, Yang MY, Ma YL, et al. Effect of Ejiao (asini corii colla) and turtle carapace glue on gut microbiota in nude mice with uterine fibroids based on High-Throughput sequencing of 16SrRNA gene[J]. Evidence-based Complementary and Alternative Medicine: eCAM, 2022, 2022: 3934877.
2024年第51卷第12期
PDF下载
63
30
引用本文
BibTeX
文章信息
doi: 10.20043/j.cnki.MPM.202403026
  • 接收时间：2024-03-01
  • 首发时间：2026-03-17
  • 出版时间：2024-06-25
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2024-03-01
基金
首都卫生发展科研专项项目(首发2018-4-4204)
北京市中医药科技发展资金项目(QN-2020-18)
作者信息
    1.北京中医药大学东方医院妇科，北京 100078
    2.北京中医药大学研究生院

通讯作者:

贡欣，E-mail：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/xdyfyx/CN/10.20043/j.cnki.MPM.202403026
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
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
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62199257
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持