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Article(id=1241329579642647233, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241329570129956900, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202501024, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1735747200000, receivedDateStr=2025-01-02, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773885634575, onlineDateStr=2026-03-19, pubDate=1752076800000, pubDateStr=2025-07-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773885634575, onlineIssueDateStr=2026-03-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773885634575, creator=13701087609, updateTime=1773885634575, updator=13701087609, issue=Issue{id=1241329570129956900, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='13', pageStart='2305', pageEnd='2496', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773885632307, creator=13701087609, updateTime=1773885763730, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241330121425080472, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241329570129956900, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241330121425080473, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241329570129956900, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2450, endPage=2458, ext={EN=ArticleExt(id=1241329580024328932, articleId=1241329579642647233, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Gut microbiome characteristics of Tibetan hyperuricemia patients in Lhasa based on metagenomic sequencing, columnId=1228016572065837304, journalTitle=Modern Preventive Medicine, columnName=Experimental Technology and Applications, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the compositional and functional differences in gut microbiota between Tibetan hyperuricemia patients and healthy controls in Lhasa.

Methods

From the Southwest China Natural Population Cohort, 108 Tibetan participants were enrolled and stratified into hyperuricemia and control groups based on serum uric acid levels. Fecal samples underwent metagenomic sequencing, with bioinformatics analyses comparing microbial composition and function. Spearman correlation and linear regression assessed phenotype-microbiome associations.

Results

Hyperuricemia patients showed significantly reduced α-diversity (W=938.000, P=0.046). Fusobacterium varium (LDA=4.315, P<0.001), Bifidobacterium pseudolongum (LDA=4.284, P=0.018), and Oscillibacter sp. PEA192 (LDA=4.259, P=0.050) were enriched in hyperuricemia, whereas Bacteroides uniformis (LDA=4.032, P<0.001), Phocaeicola dorei (LDA=3.750, P=0.028), and Bacteroides fragilis (LDA=3.945, P=0.005) predominated in controls. B. pseudolongum positively correlated with hyperuricemia (r=0.267, P=0.005), while B. uniformis showed negative association (r=-0.305, P=0.001).

Conclusion

Tibetan hyperuricemia patients exhibit gut dysbiosis characterized by reduced beneficial bacteria and increased pathogenic species, which may contribute to disease pathogenesis.

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目的

探究藏族地区高尿酸血症人群和正常人群的肠道微生物的物种构成及差异，可为藏族人群防治高尿酸血症来提供研究基础。

方法

基于西南地区自然人群队列拉萨地区的随访调查数据，根据纳排标准选择108名拉萨藏族居民作为研究对象，收集其人口学和人体测量信息、血和粪便样本，根据血清尿酸值分为高尿酸血症组和正常人群组。通过宏基因组测序测定粪便中的微生物组，采用生物信息学比较不同人群肠道微生物组的组成差异和功能差异，并使用Spearman秩相关和线性回归分析人群表型与肠道微生物的相关性。

结果

高尿酸血症人群的α多样性显著降低(W=938.000，P=0.046)。变形弗菌(Fusobacterium varium，LDA=4.315, P<0.001)、伪长双歧杆菌(Bifidobacterium pseudolongum，LDA=4.284, P=0.018)、摆动杆菌PEA192株(Oscillibacter sp. PEA192，LDA=4.259, P=0.050)等菌在高尿酸血症人群中富集，但单形拟杆菌(Bacteroides uniformis，LDA=4.032, P<0.001)、多雷菲欧克菌(Phocaeicola dorei，LDA= 3.750, P=0.028)、脆弱拟杆菌(Bacteroides fragilis，LDA=3.945, P=0.005)等菌在正常人群中富集。伪长双歧杆菌与高尿酸血症显著正相关(r=0.267, P=0.005)，单形拟杆菌与高尿酸血症显著负相关(r=-0.305, P=0.001)。

结论

藏族高尿酸血症人群的肠道微生物失调，呈现有益菌减少、有害菌增多的特征，与高尿酸血症的发生发展密切相关。

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游奴佳，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=XuBx4aM0Q60XRYDidfCUtA==, magXml=3p4PV1BJ0bAyHdS/QK5Lrw==, pdfUrl=null, pdf=yuZJaANMLTszuHa4DQpQ4w==, pdfFileSize=1652472, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=H3KDXqy2IfoDJvl+PSdqAw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=IS6nPfL2I/unjwvwyvydEA==, mapNumber=null, authorCompany=null, fund=null, authors=

袁文怡（2001—），女，硕士在读，研究方向：微生物、公众健康与检验

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袁文怡（2001—），女，硕士在读，研究方向：微生物、公众健康与检验

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袁文怡（2001—），女，硕士在读，研究方向：微生物、公众健康与检验

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Microbiome, 2022, 10(1): 195., articleTitle=Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling, refAbstract=null), Reference(id=1241329777123053679, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, doi=null, pmid=null, pmcid=null, year=2023, volume=300, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=22, authorNames=Niu C, Hu XL, Yuan ZW, journalName=Journal of Ethnopharmacology, refType=null, unstructuredReference=Niu C, Hu XL, Yuan ZW, et al. Pulsatilla decoction improves DSS-induced colitis via modulation of fecal-bacteria-related short-chain fatty acids and intestinal barrier integrity[J] . Journal of Ethnopharmacology, 2023, 300: 115741., articleTitle=Pulsatilla decoction improves DSS-induced colitis via modulation of fecal-bacteria-related short-chain fatty acids and intestinal barrier integrity, refAbstract=null), Reference(id=1241329777219522674, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, doi=null, pmid=null, pmcid=null, year=2024, volume=135, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[22], rfOrder=23, authorNames=Cao ZB, Wang XZ, Liu HJ, journalName=Phytomedicine, refType=null, unstructuredReference=Cao ZB, Wang XZ, Liu HJ, et al. Gut microbiota mediate the alleviation effect of Xiehuo-Guzheng granules on β cell dedifferentiation in type 2 diabetes mellitus[J] . Phytomedicine, 2024,135: 156151., articleTitle=Gut microbiota mediate the alleviation effect of Xiehuo-Guzheng granules on β cell dedifferentiation in type 2 diabetes mellitus, refAbstract=null)], funds=[Fund(id=1241329772148609038, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, awardId=2020YFC2008005; 2023YFC3604702; 2017YFC0907305, language=CN, fundingSource=国家重点研发计划(2020YFC2008005; 2023YFC3604702; 2017YFC0907305), fundOrder=null, country=null), Fund(id=1241329774644219919, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, awardId=2024ZYD0098, language=CN, fundingSource=四川省科技厅-中央引导地方科技发展项目(2024ZYD0098), fundOrder=null, country=null), Fund(id=1241329774757466130, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, awardId=XZ202201ZD0001G, language=CN, fundingSource=西藏自治区重大科技专项(XZ202201ZD0001G), fundOrder=null, country=null), Fund(id=1241329774849740822, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, awardId=XZ202303ZY0007G, language=CN, fundingSource=西藏自治区科技计划专项(XZ202303ZY0007G), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241329762401047048, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, xref=1., ext=[AuthorCompanyExt(id=1241329762409435657, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, companyId=1241329762401047048, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=West China School of Public Health/West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China), AuthorCompanyExt(id=1241329762417824266, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, companyId=1241329762401047048, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.四川大学华西公共卫生学院/华西第四医院，四川 成都 610041)]), AuthorCompany(id=1241329762535264788, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, xref=2., ext=[AuthorCompanyExt(id=1241329762543653398, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, companyId=1241329762535264788, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.四川大学华西医院国家老年疾病临床医学研究中心)]), AuthorCompany(id=1241329762652705313, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, xref=3., ext=[AuthorCompanyExt(id=1241329762656899617, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, companyId=1241329762652705313, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.成都市西藏自治区人民政府驻成都办事处医院骨科)]), AuthorCompany(id=1241329762862420525, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, xref=4., ext=[AuthorCompanyExt(id=1241329762866614830, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, companyId=1241329762862420525, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=4.四川省成都市四川大学华西医院骨科研究所)]), AuthorCompany(id=1241329762950500916, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, xref=5., ext=[AuthorCompanyExt(id=1241329762963083832, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, companyId=1241329762950500916, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=5.西藏自治区疾病预防控制中心)]), AuthorCompany(id=1241329763055358529, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, xref=6., ext=[AuthorCompanyExt(id=1241329763063747138, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, companyId=1241329763055358529, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=6.西藏大学)])], figs=[ArticleFig(id=1241329767501321108, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Figure 1, caption=The difference of intestinal microbial composition between the Tibetan population with hyperuricemia and the normal population, figureFileSmall=DtJP5Inl9mGVT6FUpeMHEQ==, figureFileBig=H3KDXqy2IfoDJvl+PSdqAw==, tableContent=null), ArticleFig(id=1241329767677481887, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=图1, caption=藏族HUA人群和正常人群肠道微生物组成差异

注：A为门水平下的肠道微生物差异；B为种水平下的肠道微生物差异。

, figureFileSmall=DtJP5Inl9mGVT6FUpeMHEQ==, figureFileBig=H3KDXqy2IfoDJvl+PSdqAw==, tableContent=null), ArticleFig(id=1241329767828476842, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Figure 2, caption=Comparison of relative abundance of intestinal microbiome metabolic pathways at different levels between two groups of Tibetan population

(A) Top 5 at the secondary level (B) Top 10 at the tertiary level

, figureFileSmall=TtrZzO5q4pTxnw+NXd3s2A==, figureFileBig=aRLYHcYwp/zJRbxNnaEKqQ==, tableContent=null), ArticleFig(id=1241329768088523705, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=图2, caption=藏族两组人群不同水平下肠道微生物组的代谢通路的相对丰度比较

注：A为前五的二级通路；B为前十的三级通路。

, figureFileSmall=TtrZzO5q4pTxnw+NXd3s2A==, figureFileBig=aRLYHcYwp/zJRbxNnaEKqQ==, tableContent=null), ArticleFig(id=1241329770198258623, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Figure 3, caption=Comparison of alpha and beta diversity of gut microbiota species in participants with hyperuricemia and normal populations, figureFileSmall=5Ku2PdUqNI0ITGFu62NGtg==, figureFileBig=smI9IhTIonfZoo8TwWEbVw==, tableContent=null), ArticleFig(id=1241329770353447877, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=图3, caption=藏族HUA人群和正常人群肠道微生物群种水平的α和β多样性的比较

注：A为Shannon指数；B为Simpson指数；C为PCoA分析。

, figureFileSmall=5Ku2PdUqNI0ITGFu62NGtg==, figureFileBig=smI9IhTIonfZoo8TwWEbVw==, tableContent=null), ArticleFig(id=1241329770491859911, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Figure 4, caption=Comparison of alpha and beta diversity of gut microbiota species between Tibetan hyperuricemia and normal subgroup population, figureFileSmall=kBoKqWNRJm46nFlqMuR77g==, figureFileBig=okSkUGBUNXBJXzJrHF21AQ==, tableContent=null), ArticleFig(id=1241329770647049168, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=图4, caption=藏族HUA人群和正常亚组人群肠道微生物群种水平的α和β多样性的比较

注：A为Shannon指数；B为Simpson指数；C为PCoA分析。

, figureFileSmall=kBoKqWNRJm46nFlqMuR77g==, figureFileBig=okSkUGBUNXBJXzJrHF21AQ==, tableContent=null), ArticleFig(id=1241329770739323860, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Figure 5, caption=Differential species in participants with hyperuricemia and normal populations, figureFileSmall=D28XnYZtuOo9utNWrPzXNA==, figureFileBig=kDdVooNBQOlBkPBzQrnuOA==, tableContent=null), ArticleFig(id=1241329770856764383, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=图5, caption=HUA人群和正常人群的肠道差异物种

注：A为属水平差异物种；B为种水平差异物种。

, figureFileSmall=D28XnYZtuOo9utNWrPzXNA==, figureFileBig=kDdVooNBQOlBkPBzQrnuOA==, tableContent=null), ArticleFig(id=1241329770957427687, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Figure 6, caption=Results of Spearman rank correlation analysis between differential species and population phenotypes, figureFileSmall=eWtaObQN/NVnl4bI3Vq/lQ==, figureFileBig=tvnLTgGSmiz/7DqDmRSXJg==, tableContent=null), ArticleFig(id=1241329771083256813, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=图6, caption=差异物种与人群表型Spearman秩相关分析结果

注：图中颜色根据Spearman相关系数方向进行标注，白色表示负相关，黑色表示正相关；“+”“-”代表P<0.05，“++”“--”代表P<0.01；UA尿酸；Gr肌酐；UREA尿素。

, figureFileSmall=eWtaObQN/NVnl4bI3Vq/lQ==, figureFileBig=tvnLTgGSmiz/7DqDmRSXJg==, tableContent=null), ArticleFig(id=1241329771225863156, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Figure 7, caption=Heatmap of phenotype-associated differential species based on linear regression analysis, figureFileSmall=BvRn/13LcHyunjltcO7cUA==, figureFileBig=bptLVKHTRqqRfNV73EaSpA==, tableContent=null), ArticleFig(id=1241329771410412537, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=图7, caption=基于线性回归分析的表型相关差异物种的热图

注：使用CLR对微生物组丰度数据进行转换，并对BMI、年龄、性别、吸烟状况和饮酒状况等协变量进行校正；通过分层聚类分析，基于关联Z分数（Z-score）对差异物种进行聚类；白色表示负相关，黑色表示正相关；“+”“-”代表P<0.05，“++”“--”代表P<0.01；UA尿酸；Gr肌酐；UREA尿素。

, figureFileSmall=BvRn/13LcHyunjltcO7cUA==, figureFileBig=bptLVKHTRqqRfNV73EaSpA==, tableContent=null), ArticleFig(id=1241329771582379006, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=EN, label=Table 1, caption=

Basic characteristics of Tibetan hyperuricemia population and normal population ［（），n（%），M（P25，P75）］

, figureFileSmall=null, figureFileBig=null, tableContent=
基本特征HUA组（n=33）正常组（n=75）统计量P值
年龄（岁）49.87±9.6749.94±10.35-0.0320.975
性别16.146<0.001
男26 (78.78)26 (34.67)
女7 (21.21)49 (65.33)
最高教育程度—0.826
未正规上过学14 (42.42)35 (46.67)
小学16 (48.48)28 (37.33)
初中3 (9.09)10 (13.33)
高中（包括中专/技校）0 (0.00)1 (1.33)
大学（包括研究生）0 (0.00)1 (1.33)
吸烟状况4.5090.036
吸烟9 (27.27)7 (9.33)
不吸烟/戒烟24 (72.72)68 (90.67)
饮酒状况6.1870.013
饮酒15 (45.45)15 (20.00)
从不饮酒18 (54.54)60 (80.00)
体力活动17.00 (6.41, 29.65）12.17 (7.04, 17.34)1 458.5000.141
BMI(kg/m2)27.50±2.8925.30±3.753.2910.002
腰臀比0.94 (0.91, 0.97)0.92 (0.87, 0.97)1 506.5000.040
腰高比0.60±0.050.58±0.061.3910.168
收缩压（mm Hg）115.67 (107.00, 126.33)113.00 (103.00, 128.00)1 354.0000.437
舒张压 (mm Hg)77.36±8.2878.90±11.85-0.7740.441
心率（次/分）71.13±8.8973.01±11.20-0.9330.354
空腹血糖(mmol/L)4.59 (4.29, 4.93)4.93 (4.48, 5.32)881.5000.018
糖化血红蛋白(%)5.80 (5.50, 6.20)5.80 (5.45, 6.20)1 261.5000.872
总胆固醇(mmol/L)4.37±1.104.14±1.380.8870.378
甘油三酯(mmol/L)1.22 (0.92, 1.68)0.95 (0.64, 1.27)1 674.0000.004
低密度脂蛋白 (mmol/L)2.78 (2.19, 3.12)2.23 (1.85, 2.86)1 493.0000.089
高密度脂蛋白 (mmol/L)1.04±0.331.07±0.38-0.4080.684
尿酸(μmol/L)439.00 (427.80, 500.50)284.70 (248.95, 346.35)2 423.000<0.001
尿素(mmol/L)4.48±1.264.52±1.32-0.1160.908
肌酐(μmol/L)78.92±14.1664.03±10.455.427<0.001
尿酸碱度6.00 (5.00, 6.00)6.00 (4.75, 6.00)1 174.5000.981
布里斯托粪便性状（Bristol stool scale）—0.093
性状10 (0.00)3 (4.05)
性状20 (0.00)4 (5.41)
性状30 (0.00)2 (2.70)
性状420 (62.50)40 (54.10)
性状53 (9.38)15 (20.30)
性状65 (15.60)9 (12.20)
性状74 (12.50)1 (1.35)
薯类摄入(g/w)700.00 (200.00, 1 050.00)350.00 (200.00, 700.00)1 451.0000.152
红肉及其制品(g/w)350.00 (350.00, 700.00)350.00 (212.50, 700.00)1 310.5000.619
家禽及其制品(g/w)17.50 (0.00, 100.00)17.50 (0.00, 100.00)1 212.5000.864
蛋类及其制品(g/w)120.00 (11.67, 210.00)100.00 (29.00, 250.00)1 174.0000.672
新鲜蔬菜(g/w)700.00 (350.00, 1 400.00)700.00 (650.00, 1 400.00)1 196.5000.779
豆制品(g/w)4.67 (0.00, 90.00)0.00 (0.00, 50.00)1 399.0000.230
新鲜水果(g/w)400.00 (200.00, 1 050.00)700.00 (200.00, 1 400.00)1 111.5000.398
乳类及其制品(g/w)150.00 (46.67, 700.00)200.00 (15.23, 500.00)1 258.0000.893
杂粮摄入(g/w)655.67 (354.50, 812.00)674.60 (404.50, 1 009.00)1 199.5000.802
饮茶摄入(g/w)14.00 (7.00, 33.60)28.00 (14.00, 59.50)973.5000.076
蛋白质摄入(g/w)322.19 (263.86, 432.62)312.15 (213.55, 428.92)1 315.0000.608
脂肪摄入(g/w)433.97 (273.73, 601.99)421.79 (289.37, 647.12)1 247.0000.952
碳水化合物摄入(g/w)1 804.27±624.091 709.47±689.010.7040.484
盐摄入(g/w)23.01 (8.63, 43.15)15.53 (7.98, 33.14)1 362.5000.406
糍粑摄入量(g/w)1 050.00 (560.00, 1 120.00)1 050.00 (525.00, 1 050.00)0.0550.814
藏面摄入量(g/w)1 050.00 (600.00, 1 050.00)620.00 (300.00, 1 050.00)0.5010.479
酥油茶摄入量(g/w)2 100.00 (1 050.00, 4 200.00)4 200.00 (920.00, 7 700.00)1.5710.210
), ArticleFig(id=1241329771750150144, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241329579642647233, language=CN, label=表1, caption=

藏族HUA人群和正常人群基本特征［（），n（%），M（P25，P75）］

, figureFileSmall=null, figureFileBig=null, tableContent=
基本特征HUA组（n=33）正常组（n=75）统计量P值
年龄（岁）49.87±9.6749.94±10.35-0.0320.975
性别16.146<0.001
男26 (78.78)26 (34.67)
女7 (21.21)49 (65.33)
最高教育程度—0.826
未正规上过学14 (42.42)35 (46.67)
小学16 (48.48)28 (37.33)
初中3 (9.09)10 (13.33)
高中（包括中专/技校）0 (0.00)1 (1.33)
大学（包括研究生）0 (0.00)1 (1.33)
吸烟状况4.5090.036
吸烟9 (27.27)7 (9.33)
不吸烟/戒烟24 (72.72)68 (90.67)
饮酒状况6.1870.013
饮酒15 (45.45)15 (20.00)
从不饮酒18 (54.54)60 (80.00)
体力活动17.00 (6.41, 29.65）12.17 (7.04, 17.34)1 458.5000.141
BMI(kg/m2)27.50±2.8925.30±3.753.2910.002
腰臀比0.94 (0.91, 0.97)0.92 (0.87, 0.97)1 506.5000.040
腰高比0.60±0.050.58±0.061.3910.168
收缩压（mm Hg）115.67 (107.00, 126.33)113.00 (103.00, 128.00)1 354.0000.437
舒张压 (mm Hg)77.36±8.2878.90±11.85-0.7740.441
心率（次/分）71.13±8.8973.01±11.20-0.9330.354
空腹血糖(mmol/L)4.59 (4.29, 4.93)4.93 (4.48, 5.32)881.5000.018
糖化血红蛋白(%)5.80 (5.50, 6.20)5.80 (5.45, 6.20)1 261.5000.872
总胆固醇(mmol/L)4.37±1.104.14±1.380.8870.378
甘油三酯(mmol/L)1.22 (0.92, 1.68)0.95 (0.64, 1.27)1 674.0000.004
低密度脂蛋白 (mmol/L)2.78 (2.19, 3.12)2.23 (1.85, 2.86)1 493.0000.089
高密度脂蛋白 (mmol/L)1.04±0.331.07±0.38-0.4080.684
尿酸(μmol/L)439.00 (427.80, 500.50)284.70 (248.95, 346.35)2 423.000<0.001
尿素(mmol/L)4.48±1.264.52±1.32-0.1160.908
肌酐(μmol/L)78.92±14.1664.03±10.455.427<0.001
尿酸碱度6.00 (5.00, 6.00)6.00 (4.75, 6.00)1 174.5000.981
布里斯托粪便性状（Bristol stool scale）—0.093
性状10 (0.00)3 (4.05)
性状20 (0.00)4 (5.41)
性状30 (0.00)2 (2.70)
性状420 (62.50)40 (54.10)
性状53 (9.38)15 (20.30)
性状65 (15.60)9 (12.20)
性状74 (12.50)1 (1.35)
薯类摄入(g/w)700.00 (200.00, 1 050.00)350.00 (200.00, 700.00)1 451.0000.152
红肉及其制品(g/w)350.00 (350.00, 700.00)350.00 (212.50, 700.00)1 310.5000.619
家禽及其制品(g/w)17.50 (0.00, 100.00)17.50 (0.00, 100.00)1 212.5000.864
蛋类及其制品(g/w)120.00 (11.67, 210.00)100.00 (29.00, 250.00)1 174.0000.672
新鲜蔬菜(g/w)700.00 (350.00, 1 400.00)700.00 (650.00, 1 400.00)1 196.5000.779
豆制品(g/w)4.67 (0.00, 90.00)0.00 (0.00, 50.00)1 399.0000.230
新鲜水果(g/w)400.00 (200.00, 1 050.00)700.00 (200.00, 1 400.00)1 111.5000.398
乳类及其制品(g/w)150.00 (46.67, 700.00)200.00 (15.23, 500.00)1 258.0000.893
杂粮摄入(g/w)655.67 (354.50, 812.00)674.60 (404.50, 1 009.00)1 199.5000.802
饮茶摄入(g/w)14.00 (7.00, 33.60)28.00 (14.00, 59.50)973.5000.076
蛋白质摄入(g/w)322.19 (263.86, 432.62)312.15 (213.55, 428.92)1 315.0000.608
脂肪摄入(g/w)433.97 (273.73, 601.99)421.79 (289.37, 647.12)1 247.0000.952
碳水化合物摄入(g/w)1 804.27±624.091 709.47±689.010.7040.484
盐摄入(g/w)23.01 (8.63, 43.15)15.53 (7.98, 33.14)1 362.5000.406
糍粑摄入量(g/w)1 050.00 (560.00, 1 120.00)1 050.00 (525.00, 1 050.00)0.0550.814
藏面摄入量(g/w)1 050.00 (600.00, 1 050.00)620.00 (300.00, 1 050.00)0.5010.479
酥油茶摄入量(g/w)2 100.00 (1 050.00, 4 200.00)4 200.00 (920.00, 7 700.00)1.5710.210
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基于宏基因组测序技术的拉萨藏族高尿酸血症患者肠道微生物特征研究
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袁文怡 1 , 窦青瑜 2 , 孔清泉 3, 4 , 尼玛曲措 5 , 多吉卓玛 6 , 赵星 1 , 杨淑娟 1 , 曾沛斌 1 , 游奴佳 1
现代预防医学 | 实验技术及其应用 2025,52(13): 2450-2458
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现代预防医学 | 实验技术及其应用 2025, 52(13): 2450-2458
基于宏基因组测序技术的拉萨藏族高尿酸血症患者肠道微生物特征研究
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袁文怡1, 窦青瑜2, 孔清泉3, 4, 尼玛曲措5, 多吉卓玛6, 赵星1, 杨淑娟1, 曾沛斌1, 游奴佳1
作者信息
  • 1.四川大学华西公共卫生学院/华西第四医院，四川 成都 610041
  • 2.四川大学华西医院国家老年疾病临床医学研究中心
  • 3.成都市西藏自治区人民政府驻成都办事处医院骨科
  • 4.四川省成都市四川大学华西医院骨科研究所
  • 5.西藏自治区疾病预防控制中心
  • 6.西藏大学

    • 袁文怡（2001—），女，硕士在读，研究方向：微生物、公众健康与检验

通讯作者:

游奴佳，E-mail:
Gut microbiome characteristics of Tibetan hyperuricemia patients in Lhasa based on metagenomic sequencing
Wen-yi YUAN1, Qing-yu DOU2, Qing-quan KONG3, 4, NYIMA Qu-cuo5, DORJE Zhuo-ma6, Xing ZHAO1, Shu-juan YANG1, Pei-bin ZENG1, Nu-jia YOU1
Affiliations
  • West China School of Public Health/West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China
出版时间: 2025-07-10 doi: 10.20043/j.cnki.MPM.202501024
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摘要
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目的

探究藏族地区高尿酸血症人群和正常人群的肠道微生物的物种构成及差异，可为藏族人群防治高尿酸血症来提供研究基础。

方法

基于西南地区自然人群队列拉萨地区的随访调查数据，根据纳排标准选择108名拉萨藏族居民作为研究对象，收集其人口学和人体测量信息、血和粪便样本，根据血清尿酸值分为高尿酸血症组和正常人群组。通过宏基因组测序测定粪便中的微生物组，采用生物信息学比较不同人群肠道微生物组的组成差异和功能差异，并使用Spearman秩相关和线性回归分析人群表型与肠道微生物的相关性。

结果

高尿酸血症人群的α多样性显著降低(W=938.000，P=0.046)。变形弗菌(Fusobacterium varium，LDA=4.315, P<0.001)、伪长双歧杆菌(Bifidobacterium pseudolongum，LDA=4.284, P=0.018)、摆动杆菌PEA192株(Oscillibacter sp. PEA192，LDA=4.259, P=0.050)等菌在高尿酸血症人群中富集，但单形拟杆菌(Bacteroides uniformis，LDA=4.032, P<0.001)、多雷菲欧克菌(Phocaeicola dorei，LDA= 3.750, P=0.028)、脆弱拟杆菌(Bacteroides fragilis，LDA=3.945, P=0.005)等菌在正常人群中富集。伪长双歧杆菌与高尿酸血症显著正相关(r=0.267, P=0.005)，单形拟杆菌与高尿酸血症显著负相关(r=-0.305, P=0.001)。

结论

藏族高尿酸血症人群的肠道微生物失调，呈现有益菌减少、有害菌增多的特征，与高尿酸血症的发生发展密切相关。

藏族  /  高尿酸血症  /  肠道菌群  /  宏基因组
Objective

To investigate the compositional and functional differences in gut microbiota between Tibetan hyperuricemia patients and healthy controls in Lhasa.

Methods

From the Southwest China Natural Population Cohort, 108 Tibetan participants were enrolled and stratified into hyperuricemia and control groups based on serum uric acid levels. Fecal samples underwent metagenomic sequencing, with bioinformatics analyses comparing microbial composition and function. Spearman correlation and linear regression assessed phenotype-microbiome associations.

Results

Hyperuricemia patients showed significantly reduced α-diversity (W=938.000, P=0.046). Fusobacterium varium (LDA=4.315, P<0.001), Bifidobacterium pseudolongum (LDA=4.284, P=0.018), and Oscillibacter sp. PEA192 (LDA=4.259, P=0.050) were enriched in hyperuricemia, whereas Bacteroides uniformis (LDA=4.032, P<0.001), Phocaeicola dorei (LDA=3.750, P=0.028), and Bacteroides fragilis (LDA=3.945, P=0.005) predominated in controls. B. pseudolongum positively correlated with hyperuricemia (r=0.267, P=0.005), while B. uniformis showed negative association (r=-0.305, P=0.001).

Conclusion

Tibetan hyperuricemia patients exhibit gut dysbiosis characterized by reduced beneficial bacteria and increased pathogenic species, which may contribute to disease pathogenesis.

Tibetan  /  Hyperuricemia  /  Gut microbiota  /  Metagenomics
袁文怡, 窦青瑜, 孔清泉, 尼玛曲措, 多吉卓玛, 赵星, 杨淑娟, 曾沛斌, 游奴佳. 基于宏基因组测序技术的拉萨藏族高尿酸血症患者肠道微生物特征研究. 现代预防医学, 2025 , 52 (13) : 2450 -2458 . DOI: 10.20043/j.cnki.MPM.202501024
Wen-yi YUAN, Qing-yu DOU, Qing-quan KONG, NYIMA Qu-cuo, DORJE Zhuo-ma, Xing ZHAO, Shu-juan YANG, Pei-bin ZENG, Nu-jia YOU. Gut microbiome characteristics of Tibetan hyperuricemia patients in Lhasa based on metagenomic sequencing[J]. Modern Preventive Medicine, 2025 , 52 (13) : 2450 -2458 . DOI: 10.20043/j.cnki.MPM.202501024
正文
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高尿酸血症（hyperuricemia，HUA）与痛风的患病率呈现持续增长趋势，已成为当前公共卫生领域的重要挑战[1]。该病症的核心特征表现为血液中尿酸浓度异常升高以及嘌呤代谢失调[2]。若长期处于高尿酸状态，会促使尿酸盐结晶在关节部位逐渐积聚，进而引发急性或慢性痛风性关节炎[3]。近年来，肠道微生物群与高尿酸血症的关联备受关注，然而针对藏族人群的相关研究仍较为匮乏。本研究聚焦于藏族人群，通过对比分析高尿酸血症患者与健康个体的肠道微生物组成差异，旨在填补该领域的研究空白，同时，为藏族人群高尿酸血症的防治策略奠定理论基础。
1　对象与方法
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1.1　研究对象
中国西南地区自然人群研究(Chinese multi-ethnic cohort, CMEC)在2017年启动，且在2019年9月完成基线数据收集，共纳入了99 556名参与者，随访阶段于2020年7月启动，约10%的基线人群参与了随访调查，本研究收集了2020年7—12月来自拉萨的111名藏族参与者的粪便样本[4]。收集其社会人口学、疾病史、个体测量等，男性血清尿酸浓度超过7.0 mg/dl（420 μmol/L）或女性血清尿酸浓度高于6.0 mg/dl（360 μmol/L）即可诊断为HUA，最终共纳入108名参与者（已排除一个月内服用过抗生素的人群），依据上述标准将其分为HUA组和正常组[5]。本研究已获得四川大学医学伦理委员会审批（批件号：K2020022），所有参与者充分了解研究内容并签署了知情同意书。
1.2　粪便收集
随访研究期间，所有参与者的粪便均在当日现场采集，2021年6月完成测序分析。采集过程中用无菌聚丙烯标本杯收集新鲜粪便样本，所有粪便样本在4℃下运输，保存于-80℃环境，直至对其DNA提取。
1.3　宏基因组测序和数据处理
宏基因组测序工作由诺禾致源生物信息科技有限公司（中国）完成，采用Illumina NovaSeq6000测序平台。数据处理过程中，用Kneaddata调用Trimmomatic（v.0.39）进行序列质量控制，去除接头序列和低质量读段，随后通过Bowtie2（v.2.4.5）与人类基因组的参考序列（GRCh38/hg38）比对以去除宿主污染[6]。使用Kraken2 (v.2.1.2)鉴定宏基因组的分类组成[7]，并在每个水平(门、目、科、属和种)上进行量化。使用HUMAnN3 (v.3.0.1)定量分析编码微生物代谢通路的基因[8]。
1.4　统计学处理
所有数据采用R软件（v.4.4.0）进行分析。符合正态分布的计量资料，用（）描述；而非正态分布的数据用［M（P25，P75）］来呈现。多组间差异的分析根据数据的类型选用方差分析（ANOVA）或者Wilcoxon秩和检验。计数资料用频数及构成比（%）呈现，而组间的比较用χ2检验或者Fisher确切概率法。微生物组的分析中，使用R语言的vegan包（v.2.6.4）计算香农指数（Shannon指数）和辛普森指数（Simpson指数）衡量Alpha多样性。Beta多样性使用Bray-Curtis距离分析，用主坐标分析（principal coordinate analysis, PCoA）进行可视化，置换多元方差分析（permutational multivariate analysis of variance，PERMANOVA）对组间差异显著性差异进行分析。为减少混杂因素的影响，本研究在HUA组和正常组之间进行了亚组分析。通过倾向性评分匹配（propensity score matching, PSM）方法，筛选出在性别、年龄、身体质量指数（body mass index，BMI）与HUA组相匹配的正常组亚组，并进行多样性分析。线性判别分析效应大小（linear discriminant analysis effect size, LEfSe）方法用于识别差异的菌群。为探究差异菌群和表型的关联，用线性回归（linear regression），微生物组数据以种水平相对丰度的几何均值为基准，通过中心对数变换（centered log-ratio transformation, CLR）进行归一化处理。同时，对BMI、年龄、性别、吸烟情况及饮酒情况等混杂因素进行校正，检验水准α=0.05。
2　结果
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2.1　受试者的基本信息
如表1所示，本研究共纳入108名藏族的受试者，分别为HUA组以及正常组。两组间性别、吸烟状况、饮酒状况、BMI、腰臀比、空腹血糖（FBG）、甘油三酯（TG）、尿酸、肌酐均存在统计学差异（P<0.05）。除了FBG在HUA组显著低于正常组之外，BMI、腰臀比、TG、尿酸、肌酐均为HUA组显著高于正常组。糖化血红蛋白（HbA1C）、总胆固醇（TC）、尿素、尿酸碱度（UpH）的差异在两组之间没有统计学意义。
2.2　肠道微生物物种和功能组成
通过藏族人群的肠道微生物的物种的注释结果表明，门水平上可以发现，排名前五的菌门之中，厚壁菌门（Firmicutes，H= 7.642，P=0.006，FDR=0.011）和放线菌门（Actinobacteria，H=8.016，P=0.005，FDR=0.011）相对丰度是在高尿酸血症人群中明显较高，但拟杆菌门（Bacteroidetes，H=9.680，P=0.002，FDR=0.011）在正常人群中较高，见图1A。进一步在种水平分析发现，丰度排名前10的菌种中，青春双歧杆菌（Bifidobacterium adolescentis，H=5.590，P=0.018，FDR=0.050）和产气柯林斯菌（Collinsella aerofaciens，H=14.024，P=0.001，FDR= 0.002）的相对丰度在HUA人群中较高，而普通拟杆菌(Phocaeicola vulgatus， H=4.800，P=0.029，FDR= 0.063)的相对丰度在正常人群中较高，见图1B。
通过藏族人群的肠道微生物代谢通路的注释结果表明，二级通路中，氨基酸生物合成（amino acid biosynthesis）通路等五条通路为主要的通路，排名前五的通路平均丰度之和约占总丰度的61%。三级代谢通路可以看出，主要的两个通路分别为蔗糖生物合成（PWY-7238）通路和鸟苷酸核糖核苷酸生物合成（PWY-7221）通路。以上可以看出，HUA人群和正常人群在二级和三级代谢通路的组成结构上没有表现出显著差异。见图2。
α多样性表示了物种含量、均匀度和丰富度。研究结果显示，HUA组的Shannon指数和Simpson指数均低于正常人群，见图3A、B，但仅Shannon指数的差异具有统计学意义(W=938.000，P=0.046)，两种指数的降低表明HUA人群肠道微生物物种多样性的降低。β多样性分析可用于评估不同组别间微生物群落的相似性和差异性。本研究用PCoA分析，见图3，PERMANOVA结果表明，HUA人群和正常人群物种组成的差异具有统计学意义（R2=0.034, P=0.040），见图3C。
通过PSM，从正常人群（n=75）中筛选出与HUA组（n=33）在性别、年龄和BMI上均衡匹配的正常亚组（n=33，所有P>0.05）。为了检验亚组间的多样性差异，本研究重新进行了α和β多样性的分析。结果显示，正常亚组的Shannon指数和Simpson指数与HUA组相比，差异均不具有统计学意义，见图4A、B，表明两组在物种丰富度和均匀性上的差异较小。通过PCoA分析，观察到正常亚组与HUA组的微生物群落在空间分布上有所重叠，见图4C。尽管如此，PERMANOVA分析结果表明，正常亚组与HUA组之间的微生物群落结构仍然存在显著差异（R2=0.030, P=0.017）。
2.3　差异物种分析
为深入探究两种不同人群肠道菌群的差异物种，本研究在排除非细菌界微生物的基础上，采用LEfSe分析方法，在属水平上鉴定出17个具有显著差异的菌属，见图5A，HUA组明显富集梭杆菌属(Fusobacterium，LDA=4.327, P<0.001)等8个菌属，而正常人群中明显富集拟杆菌属(Bacteroides，LDA=4.686, P<0.001)等9个菌属。在种水平分析中，见图5B，本研究共鉴定出39个差异显著的菌种，其中按LDA值排序前30位的菌种如图示，变形弗菌(LDA=4.315, P<0.001)、伪长双歧杆菌(LDA=4.284, P=0.018)、摆动杆菌PEA192株(LDA= 4.259, P=0.050)等菌在HUA人群中明显富集，而单形拟杆菌(LDA=4.032, P<0.001)、脆弱拟杆菌(LDA=3.945, P=0.005)、多雷菲欧克菌(LDA=3.750, P=0.028)等菌在正常人群中明显富集。
2.4　差异物种与人群表型的关联
计算HUA组和正常组之间的39个差异物种和3个人口学变量（年龄、性别、最高教育程度）、2个生活方式变量（吸烟情况、饮酒情况）、6个人体测量变量（BMI、布里斯托粪便性状、腰臀比、腰高比、收缩压、舒张压）、4个血生化变量（尿酸、肌酐、尿素、UpH）、14个膳食变量（蛋白质摄入量、脂肪摄入量、碳水化合物摄入量、薯类摄入量、红肉类及制品摄入量、家禽及制品摄入量、蛋类及制品摄入量、新鲜蔬菜摄入量、杂粮摄入量、饮茶摄入量、盐摄入量、糍粑摄入量、藏面摄入量、酥油茶摄入量）间的Spearman秩相关系数。如图6所示，变形弗菌(r=0.217, P=0.024)、伪长双歧杆菌(r=0.267, P=0.005)、脆性乳杆菌(Lactobacillus crispatus，r=0.236, P=0.014)等菌与HUA呈显著正相关，相反的，单形拟杆菌(r=-0.305, P=0.001)、卡克拟杆菌(Bacteroides.caccae，r=-0.191, P=0.048)、脆弱拟杆菌(r=-0.248, P=0.009)等菌与HUA显著负相关。差异物种与尿酸的关联中呈现类似的结果。此外，沙氏另枝菌(Alistipes.shahii，r=-0.227, P=0.018)和盲肠拟杆菌(Bacteroides.caecimuris，r=-0.221, P=0.022)与尿酸呈显著负相关，巨肠另枝菌(Alistipes.megaguti，r=0.239, P=0.013)与尿酸呈显著正相关；木聚糖拟杆菌(Bacteroides.xylanisolvens，r=-0.208, P=0.031)与尿素呈显著负相关，而哈尔滨产乙醇杆菌(Ethanoligenens.harbinense，r=0.236, P=0.014)与尿素呈显著正相关；阴道斯内菌(Sneathia.vaginalis，r=0.244, P=0.013)、无色小体菌(Acholeplasma.axanthum，r=0.232, P=0.018)与尿酸碱度显著正相关，多雷菲欧克菌(r=-0.201, P=0.040)、赫氏拟杆菌(Bacteroides.helcogenes，r=-0.222, P=0.023)等菌与尿酸碱度显著负相关。
本研究用多重线性回归模型，纳入BMI、年龄、性别、吸烟状况和饮酒状况等混杂因素，分析差异物种和特定表型的相关性。如图7所示，与之前的结果类似，乌氏奥尔森菌(Olsenella uli，P=0.009)、阿拉伯马赛菌(Arabia massiliensis，P<0.001)与HUA呈显著正相关，副拟杆菌CT06株(Parabacteroides sp. CT06，P=0.009)与HUA显著负相关。此外，变形弗菌(P= 0.041)与尿酸显著正相关；单形拟杆菌(P=0.036)等菌与尿素呈显著负相关，查帕西斯瘤胃球菌(Ruminococcus.champanellensis，P=0.049)、哈尔滨产乙醇杆菌(P=0.009)与尿素显著正相关；约氏乳杆菌(Lactobacillus johnsonii，P<0.001)、博尔特肠球菌(Enterocloster.bolteae， P=0.030)、阴道斯内菌(P= 0.011)、无色小体菌(P=0.032)与尿酸碱度显著正相关，口腔生物连翘坦纳菌(Tannerella.forsythia，P=0.039)与尿酸碱度显著负相关。
3　讨论
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HUA的发病机制复杂，近些年来，肠道菌群紊乱与HUA的关系日益受到重视。本研究通过宏基因组测序技术，全面讨论了藏族高尿酸血症患者与正常人群的肠道微生物组特征差异，为HUA的微生态机制研究提供了新的视角。
首先，本研究发现HUA患者的肠道微生物α多样性（Shannon指数）显著降低，提示HUA患者的肠道菌群生态系统稳定性下降，这可能削弱其对外界环境变化（如饮食、生活方式等）的适应能力，进而增加代谢紊乱的风险[9-10]。与此同时，β多样性分析显示，两组人群之间的菌群组成存在显著差异，表明HUA患者的肠道微生物群落结构与正常人群存在显著不同，这可能反映了不同代谢状态下肠道菌群的适应性变化。已有研究表明，肠道微生物多样性降低是多种代谢性疾病（如糖尿病、肥胖）中常见的现象，这表明菌群多样性可能在维持宿主代谢平衡中发挥重要作用[11]。
在菌群组成方面，本研究发现HUA患者对比正常人群，肠道中的厚壁菌门和放线菌门丰度是显著升高的，而拟杆菌门的丰度是显著降低的。这一变化提示肠道菌群的生态位平衡可能受到干扰，尤其是厚壁菌门中某些条件致病菌的过度富集和拟杆菌门中有益菌的减少[12-13]。在种水平上，HUA患者肠道中伪长双歧杆菌和变形弗菌显著富集，而单形拟杆菌和脆弱拟杆菌在正常人群中显著富集[14]。此外，伪长双歧杆菌和变形弗菌与血清尿酸水平显著正相关，而单形拟杆菌与尿酸水平呈显著负相关。这些菌群的分布特征可能反映了HUA患者肠道菌群的促炎性失调和代谢紊乱[15]。
在代谢通路方面，本研究发现HUA患者肠道微生物中富集了核苷和核苷酸生物合成类通路（如PWY-7229和PWY-6125），这些通路可能通过促进嘌呤代谢，增加尿酸生成或加剧促炎反应[16-17]。此外，正常人群中富集了前体代谢产物/能量的产生类通路（如CENTFERM-PWY和PWY-6590），这些通路通常与短链脂肪酸（如丁酸盐和乙酸盐）的合成密切相关，短链脂肪酸已被证明具有维持肠道屏障功能、抑制炎症和调节代谢的作用[18]。这些结果表明，HUA患者可能存在微生物代谢通路的功能失衡，未来可通过短链脂肪酸补充剂或饮食调整的方式改善HUA相关的代谢紊乱[19]。
本研究表明，拉萨藏族人群的肠道微生物组成具有显著独特性，与汉族人群存在明显差异。藏族人群的传统饮食以糍粑（由青稞制成的高纤维主食）和牛羊肉等红肉为主，糍粑是由青稞面、豌豆或燕麦等材料制成的。糍粑摄入与卡克拟杆菌和另枝分菌丰度显著正相关，这些菌群能够通过代谢膳食纤维生成短链脂肪酸，从而改善肠道屏障功能和宿主代谢稳态[20-21]。另一方面，红肉摄入与戈登卡特里小鼠杆菌（Muribaculum gordoncarteri）和变形弗菌丰度显著负相关，可能通过减少潜在促炎菌群的富集，降低其对肠道屏障功能的破坏[22]。这表明，糍粑等高纤维食物的摄入对益生菌的增殖具有积极作用，而红肉的适量摄入可能通过抑制致病菌群的活性在肠道微生态平衡中发挥潜在保护作用。未来针对藏族人群的饮食干预，应结合传统饮食的益处，注重膳食纤维的补充，同时合理控制红肉的摄入比例。
尽管本研究揭示了HUA与肠道微生物之间的潜在关联，但仍存在一些局限。第一，样本量较小且仅集中于拉萨藏族人群，结果的推广性可能受到影响，第二，横断面研究设计难以建立变量间的因果关系。因此，未来研究建议仍需要结合纵向队列研究和动物实验，通过多中心研究进一步验证这些发现，并深入探讨菌群失调在HUA发生和发展中的因果关系和具体机制。
综上，本研究通过宏基因组测序技术，分析了藏族HUA患者的肠道微生物组特征，揭示了肠道菌群失调与代谢通路失衡在HUA中的潜在作用，为病理生理和机制研究提供了研究基础。同时强调人群流行病学和动物实验在验证研究发现中的重要性。
基金
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  • 国家重点研发计划(2020YFC2008005; 2023YFC3604702; 2017YFC0907305)
  • 四川省科技厅-中央引导地方科技发展项目(2024ZYD0098)
  • 西藏自治区重大科技专项(XZ202201ZD0001G)
  • 西藏自治区科技计划专项(XZ202303ZY0007G)
文献
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参考文献 引证文献
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2025年第52卷第13期
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doi: 10.20043/j.cnki.MPM.202501024
  • 接收时间：2025-01-02
  • 首发时间：2026-03-19
  • 出版时间：2025-07-10
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  • 收稿日期：2025-01-02
基金
国家重点研发计划(2020YFC2008005; 2023YFC3604702; 2017YFC0907305)
四川省科技厅-中央引导地方科技发展项目(2024ZYD0098)
西藏自治区重大科技专项(XZ202201ZD0001G)
西藏自治区科技计划专项(XZ202303ZY0007G)
作者信息
    1.四川大学华西公共卫生学院/华西第四医院，四川 成都 610041
    2.四川大学华西医院国家老年疾病临床医学研究中心
    3.成都市西藏自治区人民政府驻成都办事处医院骨科
    4.四川省成都市四川大学华西医院骨科研究所
    5.西藏自治区疾病预防控制中心
    6.西藏大学

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游奴佳，E-mail:
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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
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