Article(id=1324078053667778637, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324078037817504735, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202506332, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1750348800000, receivedDateStr=2025-06-20, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793614408174, onlineDateStr=2026-11-02, pubDate=1770652800000, pubDateStr=2026-02-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793614408174, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793614408174, creator=13701087609, updateTime=1793614408174, updator=13701087609, issue=Issue{id=1324078037817504735, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='3', pageStart='385', pageEnd='576', issueExtLink='null', onlineDate='null', pubDate='1770652800000', pubDateStr='2026-02-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793614404396, creator='13701087609', updateTime=1793614474144, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1324078330420527919, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324078037817504735, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1324078330420527920, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324078037817504735, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=471, endPage=478, ext={EN=ArticleExt(id=1324078055353888846, articleId=1324078053667778637, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Multi-omics investigation of oral-gut fungal diversity and metabolic signatures in childhood asthma, columnId=1228016568949474136, journalTitle=Modern Preventive Medicine, columnName=Child and Adolescent Health, Maternal and Child Health, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the characteristic changes and co-occurrence phenomenon of oral and intestinal fungal communities in children with asthma, and to explore the relationship between fungi and metabolism in asthma pathogenesis.

Methods

Thirty asthmatic children and thirty healthy controls were enrolled. Oral swabs and fecal samples were collected for metagenomic sequencing analysis of oral and intestinal fungal communities. Untargeted metabolomics was used to detect fecal metabolites. Multivariate statistical analysis and network models were employed to decipher microbe-metabolite associations.

Results

Compared with healthy controls, asthmatic children showed significant alterations in α-diversity and β-diversity (Bray-Curtis distance) of oral and intestinal fungi. In the oral cavity, the relative abundance of genera such as Hanseniaspora and Jimgerdemannia was elevated, while that of genera such as Beauveria was reduced. In the gut, the relative abundance of the phylum Ascomycota was elevated, while genera such as Mucor showed a reduction in relative abundance. The co-occurrence network revealed shared fungi like Candida_f_Debaryomycetac along the oral-gut axis in the asthma group. Metabolomics identified significantly elevated ceramides and decreased α-linolenic acid and lysophosphatidylcholine in the asthmatic group,with Emmonsia showing a positive correlation with ceramides.

Conclusion

Altered oral-gut fungal community abundance and characteristic metabolic profile changes were associated with childhood asthma. The "oral-gut" co-occurrence of fungal communities may synergistically contribute to airway inflammation in conjunction with lipid metabolism dysregulation.

, authors=Jin-yan HUI1, Xin-feng XU1, Xin-yao JIANG1, Yu-ling BAO2, Shu-yuan CAO1, Qian WU1, authorsList=Jin-yan HUI, Xin-feng XU, Xin-yao JIANG, Yu-ling BAO, Shu-yuan CAO, Qian WU, authorCompany=null, correspAuthors=Qian WU, 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, fund=null), CN=ArticleExt(id=1324078056423436375, articleId=1324078053667778637, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=哮喘儿童口腔和肠道真菌多样性及代谢谱的多组学研究, columnId=1228016570031604578, journalTitle=现代预防医学, columnName=儿少卫生与妇幼保健, runingTitle=null, highlight=null, articleAbstract=
目的

探讨哮喘儿童口腔与肠道真菌群落的特征变化及共存现象,揭示真菌与代谢在哮喘发生发展中的关系。

方法

纳入30例哮喘儿童和30例健康对照儿童,采集咽拭子及粪便样本进行宏基因组测序分析口腔和肠道真菌群落,结合非靶向代谢组学检测粪便代谢物,通过多元统计分析与网络模型解析微生物-代谢物关联。

结果

与健康对照儿童相比,哮喘儿童的口腔与肠道真菌α多样性以及β多样性(Bray-Curtis距离)显著改变,口腔中Hanseniaspora、Jimgerdemannia等属丰度增加,Beauveria等属丰度减少;肠道中子囊菌门丰度上升,毛霉菌等属丰度减少。共现网络显示哮喘儿童的口腔和肠道存在共有真菌,如Candida_f_Debaryomycetac属。代谢组学发现哮喘儿童神经酰胺显著升高,α-亚麻酸和溶血磷脂酰胆碱降低,且Emmonsia与神经酰胺呈正相关。

结论

儿童哮喘伴随口腔-肠道真菌群落丰度改变及特征性代谢谱变化、真菌群落“口-肠”共存现象与脂质代谢异常可能协同促进气道炎症。

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惠锦言(2002—),男,硕士在读,研究方向:公共卫生

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吴倩,E-mail:
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Correlation of aspergillus skin hypersensitivity with the duration and severity of asthma[J].Monaldi Archives for Chest Disease, 2017, 87(3): 826., articleTitle=Correlation of aspergillus skin hypersensitivity with the duration and severity of asthma, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1324078056633151576, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, xref=1., ext=[AuthorCompanyExt(id=1324078056658317401, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, companyId=1324078056633151576, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Health Inspection and Quarantine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China), AuthorCompanyExt(id=1324078056666706010, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, companyId=1324078056633151576, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.南京医科大学公共卫生学院卫生检验与检疫学系,江苏 南京 211166)]), AuthorCompany(id=1324078056754786395, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, xref=2., ext=[AuthorCompanyExt(id=1324078056763175004, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, companyId=1324078056754786395, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.南京医科大学附属南京市儿童医院)])], figs=[ArticleFig(id=1324078060965867653, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=EN, label=Figure 1, caption=Changes in oral and gut fungal diversity in children with asthma, figureFileSmall=GILnSiLc0cwJmpoaIREbsw==, figureFileBig=QcakE6LjnR7F4IYFA3G0kQ==, tableContent=null), ArticleFig(id=1324078061058142342, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=CN, label=图1, caption=哮喘儿童口腔和肠道真菌微生物多样性改变

注:图A为哮喘组与对照组口腔及肠道真菌群的Chao、Sobs、Shannon和Simpson指数比较;图B为口腔和肠道菌群的PCoA及Bray-Curtis distance分析;图A采用t检验进行统计分析;图B采用Wilcoxn符号秩和检验。

, figureFileSmall=GILnSiLc0cwJmpoaIREbsw==, figureFileBig=QcakE6LjnR7F4IYFA3G0kQ==, tableContent=null), ArticleFig(id=1324078061255274631, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=EN, label=Figure 2, caption=Changes in oral and gut fungal composition in children with asthma, figureFileSmall=dSrr0QhucUe3Gx5x1BkVdg==, figureFileBig=nslz3Z3frwmJzGpnJKt/bQ==, tableContent=null), ArticleFig(id=1324078061339160712, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=CN, label=图2, caption=哮喘儿童的口腔和肠道微生物组成及变化

注:A为柱状图,显示哮喘患组与对照组口腔和粪便微真菌在门水平和属水平的相对丰度;B为两组间口腔和粪便微生物门和属水平的组间比较;采用Wilcoxon秩和检验进行统计分析,*P<0.05;**P<0.01;***P< 0.001。

, figureFileSmall=dSrr0QhucUe3Gx5x1BkVdg==, figureFileBig=nslz3Z3frwmJzGpnJKt/bQ==, tableContent=null), ArticleFig(id=1324078061418852489, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=EN, label=Figure 3, caption=Shared fungal communities in the oral cavity and gut of children with asthma, figureFileSmall=QuxY02Uh4mtA9txJpZQKhA==, figureFileBig=2KCV0DhoU7gGdxZTF5opbA==, tableContent=null), ArticleFig(id=1324078061502738570, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=CN, label=图3, caption=哮喘儿童口腔和肠道中的共有真菌群

注:A为哮喘和对照组中前 18 个共有属的相对丰度;B为哮喘组和对照组口腔和肠道微生物属的共现网络分析;C为两组口腔和肠道共有真菌群相对丰度的差异分析;*P<0.05, Wilcoxon 秩和检验。

, figureFileSmall=QuxY02Uh4mtA9txJpZQKhA==, figureFileBig=2KCV0DhoU7gGdxZTF5opbA==, tableContent=null), ArticleFig(id=1324078061590818955, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=EN, label=Figure 4, caption=Correlations between asthma-related fungal species and metabolites in feces, figureFileSmall=YKVqbutIrUJ5RENCjRIxhw==, figureFileBig=6DvZrYELtqkwHaqqXiJ34Q==, tableContent=null), ArticleFig(id=1324078061662122124, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078053667778637, language=CN, label=图4, caption=哮喘相关微生物种类与粪便代谢物之间的相关性分析

注:A为PCA,显示哮喘儿童粪便代谢组的变化;B为差异脂质代谢物的热图分析;C为粪便中差异真菌种与差异代谢物之间斯皮尔曼相关性的热图;*P<0.05,**P<0.01,斯皮尔曼检验;D为基于差异真菌群落和脂质代谢物变量关系的RDA分析;FA脂肪酰;GP甘油磷脂;GL甘油酯;SP鞘脂;ST胆固醇脂。

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哮喘儿童口腔和肠道真菌多样性及代谢谱的多组学研究
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惠锦言 1 , 徐欣丰 1 , 姜心瑶 1 , 包玉玲 2 , 曹淑源 1 , 吴倩 1
现代预防医学 | 儿少卫生与妇幼保健 2026,53(3): 471-478
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现代预防医学 |儿少卫生与妇幼保健 2026 , 53 (3) : 471 -478
哮喘儿童口腔和肠道真菌多样性及代谢谱的多组学研究
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惠锦言(2002—),男,硕士在读,研究方向:公共卫生

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惠锦言1, 徐欣丰1, 姜心瑶1, 包玉玲2, 曹淑源1, 吴倩1
作者信息
  • 1.南京医科大学公共卫生学院卫生检验与检疫学系,江苏 南京 211166
  • 2.南京医科大学附属南京市儿童医院
通讯作者:
吴倩,E-mail:
作者简介:

惠锦言(2002—),男,硕士在读,研究方向:公共卫生

Multi-omics investigation of oral-gut fungal diversity and metabolic signatures in childhood asthma
Jin-yan HUI1, Xin-feng XU1, Xin-yao JIANG1, Yu-ling BAO2, Shu-yuan CAO1, Qian WU1
Affiliations
  • Department of Health Inspection and Quarantine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
出版时间: 2026-02-10 doi: 10.20043/j.cnki.MPM.202506332
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目的

探讨哮喘儿童口腔与肠道真菌群落的特征变化及共存现象,揭示真菌与代谢在哮喘发生发展中的关系。

方法

纳入30例哮喘儿童和30例健康对照儿童,采集咽拭子及粪便样本进行宏基因组测序分析口腔和肠道真菌群落,结合非靶向代谢组学检测粪便代谢物,通过多元统计分析与网络模型解析微生物-代谢物关联。

结果

与健康对照儿童相比,哮喘儿童的口腔与肠道真菌α多样性以及β多样性(Bray-Curtis距离)显著改变,口腔中Hanseniaspora、Jimgerdemannia等属丰度增加,Beauveria等属丰度减少;肠道中子囊菌门丰度上升,毛霉菌等属丰度减少。共现网络显示哮喘儿童的口腔和肠道存在共有真菌,如Candida_f_Debaryomycetac属。代谢组学发现哮喘儿童神经酰胺显著升高,α-亚麻酸和溶血磷脂酰胆碱降低,且Emmonsia与神经酰胺呈正相关。

结论

儿童哮喘伴随口腔-肠道真菌群落丰度改变及特征性代谢谱变化、真菌群落“口-肠”共存现象与脂质代谢异常可能协同促进气道炎症。

儿童哮喘  /  真菌  /  口腔  /  肠道  /  代谢组学
Objective

To investigate the characteristic changes and co-occurrence phenomenon of oral and intestinal fungal communities in children with asthma, and to explore the relationship between fungi and metabolism in asthma pathogenesis.

Methods

Thirty asthmatic children and thirty healthy controls were enrolled. Oral swabs and fecal samples were collected for metagenomic sequencing analysis of oral and intestinal fungal communities. Untargeted metabolomics was used to detect fecal metabolites. Multivariate statistical analysis and network models were employed to decipher microbe-metabolite associations.

Results

Compared with healthy controls, asthmatic children showed significant alterations in α-diversity and β-diversity (Bray-Curtis distance) of oral and intestinal fungi. In the oral cavity, the relative abundance of genera such as Hanseniaspora and Jimgerdemannia was elevated, while that of genera such as Beauveria was reduced. In the gut, the relative abundance of the phylum Ascomycota was elevated, while genera such as Mucor showed a reduction in relative abundance. The co-occurrence network revealed shared fungi like Candida_f_Debaryomycetac along the oral-gut axis in the asthma group. Metabolomics identified significantly elevated ceramides and decreased α-linolenic acid and lysophosphatidylcholine in the asthmatic group,with Emmonsia showing a positive correlation with ceramides.

Conclusion

Altered oral-gut fungal community abundance and characteristic metabolic profile changes were associated with childhood asthma. The "oral-gut" co-occurrence of fungal communities may synergistically contribute to airway inflammation in conjunction with lipid metabolism dysregulation.

Childhood asthma  /  Fungi  /  Oral cavity  /  Gut  /  Metabolomics
惠锦言, 徐欣丰, 姜心瑶, 包玉玲, 曹淑源, 吴倩. 哮喘儿童口腔和肠道真菌多样性及代谢谱的多组学研究. 现代预防医学, 2026 , 53 (3) : 471 -478 . DOI: 10.20043/j.cnki.MPM.202506332
Jin-yan HUI, Xin-feng XU, Xin-yao JIANG, Yu-ling BAO, Shu-yuan CAO, Qian WU. Multi-omics investigation of oral-gut fungal diversity and metabolic signatures in childhood asthma[J]. Modern Preventive Medicine, 2026 , 53 (3) : 471 -478 . DOI: 10.20043/j.cnki.MPM.202506332
口腔和胃肠道是人体最大的微生物栖息地,在与微生物组相关的疾病中发挥着重要作用[1]。与微生物组的细菌组分相比,对真菌组分或所谓的真菌群落的研究相对来说仍然不足,这种研究不足源于真菌基因组资源的匮乏、检测技术的限制,以及其在微生物组中相对较低的丰度[2]。然而,最新研究表明,真菌群落的失调与炎症性肠病、代谢综合征、哮喘等多种疾病密切相关[3],且由于真菌是真核生物,它们的代谢机制复杂而独特,具有重大研究意义[4]。
近年来,多项研究揭示了真菌致敏与哮喘发病及严重程度密切关联。流行病学调查显示,热带及潮湿地区约65.6%的哮喘患者对真菌过敏原敏感,其中烟曲霉是最常见的致敏菌[5]。真菌孢子的传播,可诱发鼻痒、胸闷等前驱症状,并加重气道炎症,导致肺功能下降和哮喘控制恶化[6]。一项纳入200例哮喘患者的纵向研究表明,真菌致敏患者更需高剂量吸入性皮质类固醇,且哮喘控制不良发生率显著高于非致敏[7]。此外,中国多中心研究进一步指出,真菌致敏在哮喘患儿中的相关性高达40%,且其致哮喘风险超过尘螨和花粉[8]。
研究表明,微生物在口腔与肠道间的迁移可能影响宿主微生态平衡及疾病发生。健康人群中,口腔至肠道的真菌传播程度有限,宏基因组分析显示仅白色念珠菌和酵母菌等少数菌属存在共有[9]。而在疾病状态下,口腔来源的如白色念珠菌可在肠道显著富集,并通过甲酰甲硫氨酸或念珠菌素激活宿主炎症或代谢通路[10]。这种迁移的潜在机制可能与宿主免疫状态及菌株特异性定植能力相关,提示真菌的口腔-肠道传播在疾病发展中可能具有重要病理意义[11]。而相较于成人而言,儿童的免疫系统尚未成熟,对真菌的免疫应答较弱,可能导致真菌的定值和迁移更容易发生[12]。
代谢紊乱在哮喘的病理生理过程中发挥重要作用,而脂质代谢异常是哮喘的关键特征之一。例如,鞘脂类如鞘磷脂的减少可能通过影响气道平滑肌收缩导致气道高反应性[13],而n-3多不饱和脂肪酸(polyunsaturated fatty acid,PUFA)可通过抑制花生四烯酸代谢减少白三烯和前列腺素生成,从而缓解炎症[14]。微生物代谢产物短链脂肪酸如丁酸通过抑制2型先天淋巴细胞(group 2 innate lymphoid cells,LLC2)功能减轻气道高反应性[15]。基于上述研究发现,可以推测真菌可能通过代谢途径来影响哮喘的发生发展。
综上所诉,在本研究中,拟采用宏基因测序分析儿童口腔和肠道真菌群落的变化,探索口腔和肠道微生物群之间的共存现象,同时绘制粪便中真菌群落代谢谱,从而探索真菌微生物影响儿童哮喘发生发展的潜在作用机制。
本研究经南京医科大学伦理委员会批准[南医大伦审(2019)02080-1号],所有监护人均接收到书面知情同意。其中样本包括30名儿童哮喘患者,30名健康对照儿童,分别招募于南京医科大学附属儿童医院和江苏省中医院。儿童哮喘患者均由医生诊断认定,且为缓解期未服用抗生素患者。根据监护人陈述和既往病例,健康对照组没有呼吸系统相关疾病或特异反应。
根据E.Z.N.A. ® Soil DNA Kit(Omega Bio-tek, 美国) 试剂盒说明书对收集的咽拭子和粪便样本抽提总DNA并进行PCR扩增。使用Illumina NovaSeq(Illumina,美国)进行宏基因组测序。利用fastp软件(version 0.20.0)对原始数据进行质控。利用MEGAHIT(version 1.1.2)对优化序列进行拼接组装,将拼接结果中≥300bp的contigs作为最终的组装结果。使用MetaGene预测开放阅读框架。使用Diamond(version 0.8.35)将非冗余基因集的氨基酸序列与NR数据库进行比对,并通过 NR 库对应的分类学信息数据库获得物种注释。
称取50 mg粪便放入1.5 ml离心管中,加入1 ml超纯水,加入磁珠于组织在4 ℃下,30 Hz研磨3 min。每份样本吸取50 μl进行混合制成质控样,将样本以及质控混合物于4℃,离心半径9 cm,12 000 r/min离心15 min,并收集上清液。向剩余的沉淀物中加入1 ml预冷的甲醇,加入磁珠于低温组织研磨仪在4 ℃下,30 Hz研磨3 min。将混合物于4 ℃,离心半径9 cm,12 000 r/min离心15 min,并收集上清液。上清液每份吸取500 μl进行混匀,于4 ℃,12 000 r/min离心15 min,吸取200 μl上清放入棕色进样瓶待测,固定样本数(5个样)之间插入一个质控样本。
对于代谢组学分析,使用Dionex Ultimate 3000 UPLC(德国Dionex)结合具有加热电喷雾电离源的Q-Orbitrap-MS系统(美国Thermo Scientific)。色谱柱为C18柱(100 mm×2.1 mm,1.9 μm),柱温为40 °C。流动相A为0.1%甲酸-水,B为0.1%甲酸-乙腈。流速0.2 ml/min,进样体积为5 μl。质谱底物气流速率为10个任意单位,喷雾电压为3.0 kV,毛细管温度为320 °C,辅助气体加热器温度为30 °C。使用加热电喷雾电离源,以全扫描模式检测样品。
数据根据代谢物特征>50%和相对标准偏差≤30%的标准进行预选。随后,使用SIMCA-P14.0软件进行主成分分析(principal component analysis,PCA)以简化和降低数据的维度。用欧式距离算法分析样本组之间的整体分布。根据投影中的变量重要性≥1.0和统计显著性(FDR校正P<0.05)选择候选变量。代谢物与人类代谢组数据库(human metabolome database,HMDB)进行比较,基于正离子模式和负离子模式。
数据以(均数±标准差)表示。采用Wilcoxon秩和检验或t检验确定两组之间在α多样性、物种组成、遗传距离和炎症因子表达方面差异的显著性。上述分析使用R(version 4.4.0)进行。采用双侧检验,检验水准α=0.05。
本研究中,哮喘儿童与健康对照儿童的平均年龄分别为(6.52±2.60)和(6.06±2.78)岁;哮喘组中男女人数分别为14∶16,对照组为18∶12。两组在年龄和性别分布上无显著差异。所有受试者的体质指数均在正常范围内且均未报告被动吸烟情况。通过宏基因测序分析了健康对照儿童和哮喘儿童的口腔微生物群和肠道微生物群。与对照组相比,哮喘组的口腔真菌群和肠道真菌群的Chao和Sobs指数升高,而Simpson和Shannon指数降低,见图1A。使用主坐标分析(principal coordinate analysis,PCoA)进行β多样性分析。Bray-Curtis距离显示两组之间的口腔和肠道真菌微生物群的β多样性存在统计学显著差异,见图1B。
口腔真菌的分类组成中优势菌门依次是子囊菌门、毛霉菌门和担子菌门。前十个优势菌属依次为有孢汉逊酵母属、假裸囊菌属、Rhizophagus_f_Glomeraceae、白僵菌属、油脂酵母属、接合酵母菌属、壳二胞属、弗里德曼菌属、角蕨属和Jimgerdemannia。
肠道真菌的分类组成中优势菌门依次子囊菌门、毛霉菌门、壶菌门和担子菌门。优势菌属依次为有酵母菌属、毛霉菌属、Candida_f_Debaryomycetac、有孢汉逊酵母属、单鞭毛菌属、油脂酵母属、Patellaria、新美鞭菌属、假裸囊菌属、Rhizophagus_f_Glomeraceae、葡萄孢腔菌属和球囊霉属。
在门水平上,对照组和哮喘组口腔真菌的丰度均未有显著差异。在属水平上,哮喘儿童口腔中的有孢汉逊酵母属、Jimgerdemannia、毕赤醇母属和柄锈菌属的丰度显著增加,白僵菌和角蕨属的丰度显著下降。本研究发现哮喘儿童口腔中Candida_inconspicua、Hanseniaspora_uvarum、Penicillium_rubens、Rhizopus_delemar、Jimgerdemannia_flammicorona、Aspergillus_tanneri、Sclerotinia_sclerotiorum、Puccinia_triticina和Penicillium_expansum丰度显著上升,Ceratobasidium_theobromae、Lipomyces_starkeyi、Zancudomyces_culisetae和Beauveria_bassiana丰度显著下降。见图2A。
在门水平上,与对照组相比,哮喘组肠道中的子囊菌门丰度显著增加,毛霉菌门丰度显著降低。在属水平上,哮喘儿童肠道中的Emmonsia丰度显著增加,毛霉菌属、单鞭毛菌属、油脂酵母属和Rhizophagus_f_ Glomeraceae丰度显著下降。哮喘儿童肠道中Saccharomyces_pastorianus、Kluyveromyces_lactis、Candida_dubliniensis和Emmonsia_crescens丰度显著增加,Lipomyces_starkeyi、Piromyces_sp__E2和Mucor_ambiguus丰度显著下降。见图2B。
在口腔和肠道真菌微生物群中共存有18个共有真菌属,它们的相对丰度显示了口腔和肠道真菌之间的关系,见图3A。此外,共现网络分析显示,在对照组中只有Candida_f_Debaryomycetac在口腔和肠道中都存在。在哮喘组中,Pseudognoymascus、Candida_f_ Debaryomycetac、镰孢霉属、金德德曼尼亚属、脂酵母属口腔和肠道中同时存在,见图3B。宏基因组测序结果的种水平上分析显示,解脂耶氏酵母、Puccinia_triticina、Jimgerdemannia_flammicorona、葡萄汁有孢汉逊酵母以及Aspergillus_tanneri在哮喘儿童的口腔中相对丰度显著增加,模糊根霉和斯塔克酵母在哮喘儿童的粪便中相对丰度显著降低,见图3C。
为阐明肠道真菌微生物组功能变化及其与宿主的相互作用,本研究采用非靶向超高效液相色谱-质谱联用方法,对粪便样本代谢组进行分析。采用PCA进行降维处理,得分图表明对照组和哮喘组之间有明显分离,见图4A,并基于 VIP大于1,校正P<0.05确定差异代谢物。在粪便代谢物中,与对照组相比,苹果酸、硬脂酸、α-亚麻酸和二十碳五烯酸(eicosapentaenoic acid, EPA)呈增多趋势;溶血磷脂酰胆碱(lysophosphatidyl choline, LPC)、磷脂酰胆碱(phosphatidyl cholines , PC)和磷脂酸(phosphatidic acid)呈减少趋势,而左旋肉碱和干鞘脂类的神经酰胺(ceramide)呈增加趋势,见图4B。通过LEfSe(linear discriminant analysis effect size)分析确定了粪便样本中LDA分数大于2的真菌属,对儿童相关哮喘相关的真菌与差异代谢物数据进行了相关性热图分析以及冗余分析(redundancy analysis,RDA),相关性热图分析显示模糊根霉、Piromyces_sp._E2、斯塔克酵母与脂肪酸、甘油酯以及甘油磷脂类代谢物呈正相关,与神经酰胺类代谢物呈负相关,而Emmonsia_crescens、都柏林念珠菌、乳酸克鲁维酵母、巴氏酵母则呈现相反的趋势,见图4C。RDA揭示了与儿童哮喘相关的真菌与必需代谢通路中的特征代谢物之间复杂的共现模式和相关性,在哮喘儿童斯塔克酵母、Emmonsia_crescens与甘油磷脂(LPC、PC 和 磷脂酸)呈负相关。乳酸克鲁维酵母、都柏林念珠菌、Emmonsia_crescens、巴氏酵母与 L - 肉碱和 神经酰胺 呈正相关,Piromyces_ sp._E2以及模糊根霉则表现得与之相反,见图4D。
本研究采用宏基因组测序,发现哮喘组儿童较对照组口腔和肠道真菌群多样性以及组成发生显著性改变,并且口腔和肠道的真菌菌属存在共存现象。通过代谢组学分析,发现肠道菌群中的差异真菌对脂质代物(如神经酰胺)存在调节作用。
本研究发现哮喘儿童口腔和肠道真菌群落的α和β-多样性均有显著性的变化,其中Sobs和Chao指数升高而Simpson和Shannon指数降低提示哮喘组中真菌群落的物种多样性增加但物种均匀程度降低。与部分成人气道研究报道哮喘患者真菌α多样性变化趋势一致[16],此变化可能与其暴露环境、免疫状态及治疗干预等因素有关。一方面,哮喘儿童可能更频繁接受抗生素和皮质类固醇治疗,这些治疗会破坏原有的菌群平衡,减弱细菌对真菌的竞争压力,导致真菌群落丰富程度扩大[17];另一个可能原因是哮喘相关炎症改变了黏膜环境,例如黏液分泌或局部pH变化,为更多真菌种提供了生存空间[18]。
本研究发现哮喘患儿口腔和肠道真菌群落组成呈现特异性改变。口腔中Hanseniaspora属的显著增殖可能与哮喘患儿频繁使用吸入性皮质类固醇(inhaled corticosteroids,ICS)相关,研究显示ICS治疗会降低口腔上皮细胞β-防御素表达,从而减弱对Hanseniaspora等酵母类真菌的清除能力[19]。另外,Chopra等人[20]在研究中发现Aspergillus Fumigatus可能与更严重的哮喘和呼吸道症状有关,即曲霉皮肤超敏反应呈阳性的患者哮喘的严重程度更高。值得注意的是,Beauveria的显著减少可能削弱其对条件致病菌的抑制作用,该菌属可通过分泌白僵菌素抑制念珠菌生物膜形成,其缺失可能为其他机会致病菌创造定植机会[5]。肠道真菌组成变化主要表现为子囊菌门的增殖和毛霉菌门的抑制。子囊菌门包含多种代谢活跃的酵母菌(如念珠菌属),其丰度增加可能与哮喘患儿肠道低氧微环境相关
本研究发现口腔-肠道真菌共现性增强,尤其发现白色念珠菌在口腔和肠道均富集。儿童免疫系统发育不成熟可能削弱对真菌的免疫清除能力,导致迁移菌株更易定植[21]。例如,Chen等[22]发现口腔和肠道样本中的大多数真菌属于共有种。口腔中的白色念珠菌可随唾液吞咽进入胃肠道,当肠道菌群受损(如抗生素后)时,这些菌株能在肠道内过度增殖[18]。哮喘患者常伴随肠道黏膜屏障功能受损,口腔真菌可能通过受损上皮细胞间隙或微褶皱细胞介导的主动转运进入肠道[15]。此外,真菌的定植能力差异也可能影响其迁移效率。例如,解脂耶氏酵母和Aspergillus tanneri等菌株可通过分泌蛋白酶或形成生物膜增强对肠道环境的适应性[23]。另外,口腔微生物被吸入肺部或经胃肠道传播已被证实可影响系统免疫[24],因此口腔-肠道真菌共现性增强提示了整个消化系统中的菌群共适应和免疫-炎症交互。
在多组学分析中,差异真菌与哮喘相关脂质代谢改变的相关性值得深入探讨。本研究发现哮喘组神经酰胺显著增加、LPC/PC下降以及PUFA减少。神经酰胺是鞘脂代谢的重要中间体,可通过激活NLRP3炎症小体促进Th2型细胞因子分泌,加剧气道高反应性[25]。有研究指出,肥胖哮喘患者的支气管内分泌物中C16:0和C24:0神经酰胺水平显著高,提示鞘磷脂代谢向神经酰胺积累偏移与哮喘的严重程度相关。而真菌感染或定植可激发宿主产生应激反应,如内源性脱氧胆酸或Toll样受体信号传导途径激活,也可能促进肺部细胞合成更多鞘脂以调节炎症[26]。LPC与PC是炎症调节中的关键分子,通常由磷脂酶A2作用产生。然而,本研究中观察到哮喘组口腔/肠道LPC/PC下降,可能反映机体或微生物消耗LPC以生成其它炎症介质,或磷脂降解通路被改变。另外有些真菌如念珠菌属可分泌酯酶样物质,其生成的脂质产物或许影响局部脂质通路[27]。n-3 PUFA具有抗炎作用,其水平下降可能降低对气道炎症的抑制。高n-3/n-6比值可降低哮喘标志物如呼气NO,提高哮喘控制率,本研究发现n-3 PUFA减少,与其作为哮喘保护因子的角色相符[28]。
本研究仍存在局限。首先本研究采用样本量较少,且收集自单一地区的儿童群体,可能导致统计效力相对不足,以及部分真菌群落或代谢物差异存在统计偏差。此外,本研究未对哮喘儿童ICS使用情况进行分析,因而难以完全排除药物治疗对真菌群落组成的潜在干扰。未来应扩大样本量,并尽可能哮喘严重程度和 ICS 等临床信息进行分层分析,以提高结果的稳健性和推广性[29]。其次研究采用横断面设计,无法证明真菌群与哮喘之间的因果关系。此外,本研究代谢组学检测仅限于粪便样本,因而无法明确区分代谢物来源于宿主还是微生物,也无法揭示代谢物作用的方向性。目前本研究结果表明,真菌群落与脂质代谢之间存在统计学上的相关性,但尚未能证实两者之间存在直接的因果关联[30]。
综上所述,本研究揭示儿童哮喘患者口腔-肠道真菌群的差异和共有现象及对代谢谱的影响,提示真菌微生态失衡与脂质代谢紊乱的协同作用可能是驱动哮喘炎症的重要机制。

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2026年第53卷第3期
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doi: 10.20043/j.cnki.MPM.202506332
  • 接收时间:2025-06-20
  • 首发时间:2026-11-02
  • 出版时间:2026-02-10
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  • 收稿日期:2025-06-20
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    1.南京医科大学公共卫生学院卫生检验与检疫学系,江苏 南京 211166
    2.南京医科大学附属南京市儿童医院

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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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