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Article(id=1322934544223056387, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1322934508630180057, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202404133, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1714233600000, receivedDateStr=2024-04-28, revisedDate=1726588800000, revisedDateStr=2024-09-18, acceptedDate=null, acceptedDateStr=null, onlineDate=1793341774277, onlineDateStr=2026-10-30, pubDate=1738166400000, pubDateStr=2025-01-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793341774277, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793341774277, creator=13701087609, updateTime=1793341774277, updator=13701087609, issue=Issue{id=1322934508630180057, tenantId=1146029695717560320, journalId=1319373162502258839, year='2025', volume='47', issue='2', pageStart='101', pageEnd='192', issueExtLink='null', onlineDate='null', pubDate='1738166400000', pubDateStr='2025-01-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793341765792, creator='13701087609', updateTime=1793341765792, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=168, endPage=176, ext={EN=ArticleExt(id=1322934544420188676, articleId=1322934544223056387, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Diversity and composition changes of intestinal fungi in patients with chronic kidney disease, columnId=1320435174995772212, journalTitle=Journal of Army Medical University, columnName=Clinical Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective‍

To analyze the diversity and composition changes of gut fungal communities between patients with chronic kidney disease （CKD） and healthy controls.

Methods‍

A total of 8 CKD patients admitted in Department of Nephrology of our hospital，and another 5 age- and gender-matched healthy individuals were recruited in this study. Fresh fecal samples were collected from the CKD patients and healthy controls. ITS DNA sequencing was employed to determine the composition of intestinal fungi，and then bioinformatics analysis was applied to compare the differences in fungal community diversity，structure，and function between the 2 groups.

Results‍

There were no statistical differences between the 2 groups in terms of age，gender composition，BMI，and so forth. The results of Alpha diversity assessment showed statistical differences were observed in Simpson index and Shannon index in the intestinal fungi between the 2 groups （P<0.01）. So was in the Beta diversity between them （P<0.01）. The relative abundance of Candida was increased significantly （P<0.01），while those of Cladosporium and Penicillium were decreased in the CKD group （P<0.05）. LEfSe analysis revealed that Candida was significantly enriched in CKD patients，whereas Cladosporium and Penicillium were significantly lower in abundance when compared to the healthy control group.

Conclusion‍

The composition of intestinal fungi in CKD patients is different from that in healthy individuals，exhibiting characteristic changes. Dysfunction of gut fungal flora may promote the progression of CKD. Regulating gut fungi and restoring gut microbiota homeostasis may become a new strategy for CKD treatment.

, authors=Huichao XIE1, Weidong XIAO1, Ben HAN2, Lihua SUN1, Yihui CHEN1, authorsList=Huichao XIE, Weidong XIAO, Ben HAN, Lihua SUN, Yihui CHEN, authorCompany=null, correspAuthors=Yihui CHEN, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2025 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, 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=1322934545481347600, articleId=1322934544223056387, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=慢性肾脏病患者肠道真菌多样性及构成改变, columnId=1322185541475488183, journalTitle=陆军军医大学学报, columnName=临床医学, runingTitle=null, highlight=null, articleAbstract=
目的

研究慢性肾脏病（chronic kidney disease，CKD）患者和健康对照者肠道真菌多样性和组成的差异。

方法

收集在陆军军医大学第二附属医院肾内科就诊的8名CKD患者；并招募与其年龄、性别相匹配的5名健康对照者。采集CKD患者（n=8）和健康对照者（n=5）的新鲜粪便样本，利用ITS DNA测序技术确定肠道真菌组成，进而利用生物信息学手段比较2组间真菌菌群多样性、结构和功能的特征差异。

结果

CKD组和健康对照组在年龄、性别构成和BMI等方面均无统计学差异。2组肠道真菌的Alpha多样性评估结果表明，Simpson指数和Shannon指数存在统计学差异（P<0.01），Beta多样性存在统计学差异（P<0.01）。CKD患者中Candida （假丝酵母属）相对丰度显著增加（P<0.01），而Cladosporium （枝孢霉属）和Penicillium （青霉属）相对丰度显著下降（P<0.05）。线性判别分析（LEfSe）表明，CKD患者个体中Candida 显著富集，而Cladosporium和Penicillium的存在量则明显少于健康对照组。

结论

CKD患者的肠道真菌组成与健康人群不同，呈现特定的变化。肠道真菌菌群失调可能促进CKD的进展。调节肠道真菌、恢复肠道微生物稳态可能成为CKD治疗的一种新策略。

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陈弈辉，E-mail：
CHEN Yihui，E-mail：
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A：使用Chao指数、Simpson指数、Shannon指数和Pd指数评估Alpha多样性；a：P<0.01，与Control组比较；B：通过应用基于Bray-Curtis距离算法的主坐标分析（PCoA）和基于Jaccard的非度量多维尺度分析（NMDS）评估Beta多样性

, figureFileSmall=s+mFx0KwOp8y/OFYfvp4gg==, figureFileBig=oGR+nJChnXYFfL64Y7fpsQ==, tableContent=null), ArticleFig(id=1322934550413849154, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934544223056387, language=EN, label=null, caption=null, figureFileSmall=WdiOonITj5BqJNX7Uq5cUQ==, figureFileBig=Ry9YtJiaiABFJiWE2RLXrA==, tableContent=null), ArticleFig(id=1322934550506123843, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934544223056387, language=CN, label=图2, caption=CKD患者与健康受试者肠道真菌菌群组成结构分析

A：属水平物种韦恩图；B：属水平物种相对丰度；C：属水平物种Circos图；D：属水平物种聚类热图

, figureFileSmall=WdiOonITj5BqJNX7Uq5cUQ==, figureFileBig=Ry9YtJiaiABFJiWE2RLXrA==, tableContent=null), ArticleFig(id=1322934550573232708, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934544223056387, language=EN, label=null, caption=null, figureFileSmall=WypRtyTfK9a8X2R7rL5M1w==, figureFileBig=DJ0A4KghHFCqjrg4ELdVUQ==, tableContent=null), ArticleFig(id=1322934550644535877, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934544223056387, language=CN, label=图3, caption=CKD患者与健康受试者肠道真菌菌群物种分析

A：属水平物种进化树图；B：属水平物种相关网络图；C：LEfSe多级物种层级树图；D：属水平差异菌相对丰度；a：P<0.05，b：P<0.01，与Control组比较

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A：KEGG酶功能丰度差异火山图，P<0.05，Fold Change>2；B：KEGG酶功能丰度热图；C：MetaCyc通路活性丰度差异火山图，P<0.05，Fold Change>2；D：MetaCyc通路活性丰度热图；E：FUNGuild功能分类柱状图

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临床特征Control组（n=5）CKD组（n=8）P
年龄/岁50.2±3.551.5±3.90.549
性别［n（%）］1.000
男3 （60.0）6 （75.0）
女2 （40.0）2 （25.0）
BMI/（kg/m2）24.8±3.022.6±3.10.239
糖尿病［n（%）］1.000
是0 （0）1 （12.5）
否5 （100.0）7 （87.5）
高血压［n（%）］1.000
是1 （20.0）1 （12.5）
否4 （80.0）7 （87.5）
), ArticleFig(id=1322934552515195466, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322934544223056387, language=CN, label=表1, caption=

CKD患者与健康对照人群临床特征比较

, figureFileSmall=null, figureFileBig=null, tableContent=
临床特征Control组（n=5）CKD组（n=8）P
年龄/岁50.2±3.551.5±3.90.549
性别［n（%）］1.000
男3 （60.0）6 （75.0）
女2 （40.0）2 （25.0）
BMI/（kg/m2）24.8±3.022.6±3.10.239
糖尿病［n（%）］1.000
是0 （0）1 （12.5）
否5 （100.0）7 （87.5）
高血压［n（%）］1.000
是1 （20.0）1 （12.5）
否4 （80.0）7 （87.5）
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慢性肾脏病患者肠道真菌多样性及构成改变
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谢会超 1 , 肖卫东 1 , 韩奔 2 , 孙力华 1 , 陈弈辉 1
陆军军医大学学报 | 临床医学 2025,47(2): 168-176
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陆军军医大学学报 |临床医学 2025 , 47 (2) : 168 -176
慢性肾脏病患者肠道真菌多样性及构成改变
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谢会超1, 肖卫东1, 韩奔2, 孙力华1, 陈弈辉1
作者信息
  • 1陆军军医大学（第三军医大学）第二附属医院 普通外科，重庆
  • 2陆军军医大学（第三军医大学）第二附属医院 营养科，重庆
通讯作者:
陈弈辉，E-mail：
CHEN Yihui，E-mail：
Diversity and composition changes of intestinal fungi in patients with chronic kidney disease
Huichao XIE1, Weidong XIAO1, Ben HAN2, Lihua SUN1, Yihui CHEN1
Affiliations
  • 1Department of General Surgery, Second Affiliated Hospital，Army Medical University （Third Military Medical University），Chongqing，China
  • 2Department of Nutrition, Second Affiliated Hospital，Army Medical University （Third Military Medical University），Chongqing，China
出版时间: 2025-01-30 doi: 10.16016/j.2097-0927.202404133
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摘要
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目的

研究慢性肾脏病（chronic kidney disease，CKD）患者和健康对照者肠道真菌多样性和组成的差异。

方法

收集在陆军军医大学第二附属医院肾内科就诊的8名CKD患者；并招募与其年龄、性别相匹配的5名健康对照者。采集CKD患者（n=8）和健康对照者（n=5）的新鲜粪便样本，利用ITS DNA测序技术确定肠道真菌组成，进而利用生物信息学手段比较2组间真菌菌群多样性、结构和功能的特征差异。

结果

CKD组和健康对照组在年龄、性别构成和BMI等方面均无统计学差异。2组肠道真菌的Alpha多样性评估结果表明，Simpson指数和Shannon指数存在统计学差异（P<0.01），Beta多样性存在统计学差异（P<0.01）。CKD患者中Candida （假丝酵母属）相对丰度显著增加（P<0.01），而Cladosporium （枝孢霉属）和Penicillium （青霉属）相对丰度显著下降（P<0.05）。线性判别分析（LEfSe）表明，CKD患者个体中Candida 显著富集，而Cladosporium和Penicillium的存在量则明显少于健康对照组。

结论

CKD患者的肠道真菌组成与健康人群不同，呈现特定的变化。肠道真菌菌群失调可能促进CKD的进展。调节肠道真菌、恢复肠道微生物稳态可能成为CKD治疗的一种新策略。

慢性肾脏病  /  肠道真菌  /  ITS DNA  /  肠道微生物稳态
Objective‍

To analyze the diversity and composition changes of gut fungal communities between patients with chronic kidney disease （CKD） and healthy controls.

Methods‍

A total of 8 CKD patients admitted in Department of Nephrology of our hospital，and another 5 age- and gender-matched healthy individuals were recruited in this study. Fresh fecal samples were collected from the CKD patients and healthy controls. ITS DNA sequencing was employed to determine the composition of intestinal fungi，and then bioinformatics analysis was applied to compare the differences in fungal community diversity，structure，and function between the 2 groups.

Results‍

There were no statistical differences between the 2 groups in terms of age，gender composition，BMI，and so forth. The results of Alpha diversity assessment showed statistical differences were observed in Simpson index and Shannon index in the intestinal fungi between the 2 groups （P<0.01）. So was in the Beta diversity between them （P<0.01）. The relative abundance of Candida was increased significantly （P<0.01），while those of Cladosporium and Penicillium were decreased in the CKD group （P<0.05）. LEfSe analysis revealed that Candida was significantly enriched in CKD patients，whereas Cladosporium and Penicillium were significantly lower in abundance when compared to the healthy control group.

Conclusion‍

The composition of intestinal fungi in CKD patients is different from that in healthy individuals，exhibiting characteristic changes. Dysfunction of gut fungal flora may promote the progression of CKD. Regulating gut fungi and restoring gut microbiota homeostasis may become a new strategy for CKD treatment.

chronic kidney disease  /  fungi  /  ITS DNA  /  gut microbiota homeostasis
谢会超, 肖卫东, 韩奔, 孙力华, 陈弈辉. 慢性肾脏病患者肠道真菌多样性及构成改变. 陆军军医大学学报, 2025 , 47 (2) : 168 -176 . DOI: 10.16016/j.2097-0927.202404133
Huichao XIE, Weidong XIAO, Ben HAN, Lihua SUN, Yihui CHEN. Diversity and composition changes of intestinal fungi in patients with chronic kidney disease[J]. Journal of Army Medical University, 2025 , 47 (2) : 168 -176 . DOI: 10.16016/j.2097-0927.202404133
正文
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慢性肾脏疾病（chronic kidney disease，CKD）是一项被公认的严重公共卫生挑战，其以肾功能受损为主要特征，并且具有高发病率和高致死率［1］。CKD会对人体的水电解质和酸碱平衡、血压调节、毒素和废物的排泄、维生素D代谢和激素调节等多个生理过程造成影响，因此患者可能出现高钾血症、高磷血症、慢性代谢性酸中毒，以及骨退化等疾病风险［2］。许多科学研究已经证明，CKD会对患者的肠道微生物产生巨大的影响［3-7］。CKD患者体内尿素增多会促进肠道中脲酶阳性菌的生长。脲酶阳性菌对大量尿素进行水解产生氨气，从而引起酸碱平衡失调和肠道环境异常。这些变化会刺激致病菌如拟杆菌门、变形菌门和厚壁菌门的生长，导致肠道来源毒素增加，破坏肠道保护屏障，加速肾脏损害的发展。
肠道真菌在肠道微生物群中扮演着重要的角色，并对肠道的功能发挥着重要作用［8］。与肠道细菌相比，肠道中的真菌更加不稳定，且在患病时经常发生变化［9］。炎症性肠病患者的肠道内白色念珠菌增多，酿酒酵母菌减少，同时担子菌门/子囊菌门的比值增大［10］。一些研究指出，肠道真菌能够与免疫系统相互作用，通过先天免疫受体Dectin-1对结肠炎的发生和发展具有一定的保护作用［11］。然而，当肠道环境发生异常变化时，肠道内的真菌可能会加速疾病的发展，给人体健康带来不利影响。一项研究发现，重症监护室患者携带肠道念珠菌会增加罹患念珠菌血症的风险［12］。此外，真菌的菌丝可以侵入不同器官，如肾脏、肝脏、脾脏、肺和大脑，从而造成损害。小鼠感染念珠菌模型中，肾脏是寄主体内真菌数量最多的器官［13］。目前尚未有关于CKD患者肠道真菌的研究报道，因此本研究旨在通过对CKD患者和健康对照群体的肠道真菌菌群组成进行研究，找出CKD患者肠道真菌的生物标志物，为临床诊疗提供支持。
1　资料与方法
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1.1　研究对象
收集在陆军军医大学第二附属医院肾内科就诊的8名CKD患者；并招募与其年龄、性别相匹配的5名健康对照者（Control）。纳入标准：年龄18～75岁；以2022年的《慢性肾脏病早期筛查、诊断及防治指南》为诊断依据，符合CKD诊断标准；自愿参加研究并签署知情同意书；无其他长期疾病，如高血压、病毒性肝炎、糖尿病、甲状腺功能亢进等。该临床研究方案已获得陆军军医大学第二附属医院医学伦理委员会的批准（2018-006-02号），所有受试者均书面同意。
1.2　粪便收集和ITS DNA测序
将新鲜粪便放入无菌采样管中，送至实验室后分装到1.5 mL无菌EP管中，液氮快速冷冻后储存在-80 ℃下。利用美国OmegaBio-Tek公司生产的E.Z.N.A.®soilDNAKit，从受试者的粪便样本中提取总微生物基因组DNA。利用引物ITS1F和ITS2R对ITS基因进行扩增。ITS1F引物的序列为5´-CTTGGTCATTT-AGAGAGAGAAGTAA-3´，ITS2R引物的序列为5´-GC-TGCGTTCTTCATCGATGC-3´。将经纯化处理的扩增子等摩尔量合并，并在IlluminaMiseqPE300平台（Illumina，美国）上，按照上海美吉生物医药科技有限公司的标准方案，进行成对末端测序。
1.3　ITS序列分析
通过美吉生物数据挖掘系统（https://report.majorbio.com）和R包ggplot2（3.4.4）完成数据挖掘和图形表示。
1.4　统计学分析
对于人群年龄和BMI的统计分析，用x¯±s表示，而其他特征则表示为n （%），使用Wilcox秩和检验或χ2检验比较CKD组和Control组之间是否存在统计学差异。使用table1 （1.4.3） R包制作和分析图表。利用Chao指数（估计样本中的物种总数）、Simpson指数（表征物种分布的多样性和均匀度）、Shannon指数（反映样本分类总数及其占比）和Pd指数（反映群落谱系多样性）来衡量Alpha多样性。通过使用基于Bray-Curtis距离算法的主坐标分析（principal co-ordinates analysis，PCoA）和基于Jaccard相似性指数的非度量多维尺度分析（non-metric multidimensional scaling，NMDS）评估Beta多样性。利用Wilcox秩和检验和独立样本t检验来对比不同组之间的群落差异。
2　结果
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2.1　研究人群特征
研究对象涉及CKD患者和健康对照群体，CKD患者包括8名被调查者（男性6名，女性2名），健康对照群体包括5名被调查者（男性3名，女性2名）。2组在年龄、性别比例、BMI、是否有糖尿病史和高血压史等方面均无统计学差异。见表1。
2.2　组间肠道真菌菌群多样性分析
对13例样本进行过滤，共筛选获得837 788条经过优化的序列，平均每个样本为64 445条，其中CKD组获得521 484条，Control组获得316 304条。通过使用qiimedada2denoise-paired方法，采用DADA2命令对序列进行去噪处理，获得了679个ASVs。使用Chao指数、Simpson指数、Shannon指数和Pd指数来评估Alpha多样性。分析结果显示，2组之间的Simpson指数和Shannon指数存在统计学差异（P<0.01，图1A）。利用Bray-Curtis距离算法的主坐标分析（PCoA）和基于Jaccard的非度量多维尺度分析（NMDS）对Beta多样性进行评估。使用Anosim非参数检验表明Control组与CKD组之间的Beta多样性存在统计学差异（P<0.01），而NMDS的应力值（Stress<0.2）显示本次分析结果稳定可靠（图1B）。
2.3　组间肠道真菌菌群组成结构分析
在属水平上，Control组共有112个菌属，而CKD组共有95个菌属。Control组和CKD组各自独有的菌属数量分别为60个和43个，2组共同拥有的菌属数量为52个（图2A）。为了进一步研究2组菌群构成的差异，分析属水平上丰度前10个优势菌属，依次是Candida （假丝酵母属）、Saccharomyces （酿酒酵母属）、unclassified_f__Aspergillaceae、unclassified_f__Metschni-kowiaceae、Aspergillus （曲霉属）、Debaryomyces （德巴利酵母属）、Penicillium （青霉属）、Cladosporium （枝孢霉属）、Wickerhamomyces （威克汉姆酵母属）、unclassified_o__Saccharomycetales。其中Control组的肠道真菌组成种类更加丰富，以unclassified_f__Aspergillaceae和unclassified_f__Metschnikowiaceae为主要类型。CKD组的肠道真菌组成更为单一，主要包括Candida和Saccharomyces（图2B、C）。Candida通常认为是肠道中最主要的潜在病原微生物。与Control组相比，CKD组的Candida 相对丰度明显增加（图2D）。
2.4　组间肠道真菌菌群物种分析
为了深入研究2组菌群之间的相互作用关系并确定优势物种，构建物种系统发生进化树和物种关联网络。在属水平上，Candida 的丰度最高，与其他真菌属的亲缘关系较为遥远（图3A）。Ascomycota （子囊菌门）在门水平上展现了显著的优势，其内部各菌群之间联系紧密，整体联通性较高。Candida 在属水平上具有最高的丰度，同时具有较高的联通性（图3B）。本研究利用线性判别分析（linear discriminant analysis effect size，LEfSe）来识别具有显著差异的生物标志物，以进一步确认不同群体之间的差异。有26种物种在2组中显著不同，Control组富含22种，CKD组富含4种（图3C）。CKD组的物种主要为Candida ，相对于Control组，其数量显著增加（P＜0.01）。相较于CKD组，Control组在属水平上表现出明显增加的物种，主要是Cladosporium和Penicillium。与Control组相比，CKD组中Candida的相对丰度明显增高（P＜0.01），而Cladosporium和Penicillium的相对丰度明显下降（P＜0.05，图 3D）。
2.5　组间肠道真菌菌群功能分析
为了探究CKD患者和健康受试者的菌群功能差异，用基于KEGG和MetaCyc的PICRUST2功能预测进行进一步研究，结果显示2组之间存在明显功能差异。通过对CKD组和Control组基于KEGG预测的酶功能相对丰度进行对比分析发现，与Control组相比，CKD组中有4个酶功能明显增强，而有176个酶功能明显减弱（图4A、B）。在对CKD组和Control组基于MetaCyc预测的通路活性相对丰度进行比较分析时发现，与Control组相比，CKD组有9条通路的活性显著下降（图4C、D）。FUNguild可以从生态功能角度探讨真菌。根据FUNguild预测结果，2组肠道真菌主要的营养方式为Saprotroph （腐生）（图4E）。与Control组相比，CKD组中相对丰度显著上升的是Undefined Saprotroph。
3　讨论
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3.1　CKD患者肠道真菌菌群特点
本研究利用ITS高通量测序技术分析患有CKD的患者和健康受试者的肠道真菌菌群。结果显示，2组之间评估Alpha多样性的Simpson指数和Shannon指数存在统计学差异（P<0.01），Beta多样性也呈现出显著差异（P<0.01），表明患有CKD的患者肠道真菌菌群在多样性和组成上发生了改变。通过LEfSe分析，本研究鉴定出在不同组群之间存在显著差异的生物标志物，包括Candida、Cladosporium和Penicillium。与Control组相比，CKD组Candida相对丰度显著增加，且存在统计学差异（P<0.01）。CKD组中Cladosporium和Penicillium的相对丰度明显少于Control组（P <0.05）。
3.2　肠道菌群与CKD的关系
近年来，CKD的发病率、病死率和合并心血管疾病发病率逐年升高［14］。CKD的危险因素有糖尿病、高血压、肥胖和高龄［15］。多种因素可以导致CKD的进展，例如微血管损伤、代谢变化、氧化应激、慢性炎症和纤维化等，最终导致不可逆转的肾单位损失、肾脏再生能力减弱，甚至发展至终末期肾病，危及生命［16-17］。目前，CKD的治疗手段相对匮乏，仅能拖延疾病恶化，迫切需要研发新的疗法以阻止或逆转CKD的发展。肠道微生物组与CKD之间存在紧密联系，已有许多研究支持这一观点。CKD患者中，疣微菌门、脱硫弧菌和梭状芽孢杆菌数量明显增多，而阿克曼菌和放线菌门数量减少［18］。病原微生物的增殖过多和代谢产物堆积会引发免疫系统过度激活，造成肠屏障功能受损和过度炎症反应，加重CKD的进展，最终导致尿毒症、肾衰竭等末期疾病［4］。
3.3　肠道Candida的丰度增加与CKD进展的关系
真菌不仅是传染病的研究对象，还是人体肠道共生微生物的重要组成部分，并在炎症性肠病［19］、结直肠癌［20］、哮喘［21］、肝硬化［22］、糖尿病［23］和精神分裂症［24］等疾病中扮演着关键角色。然而，很少有研究报道有关CKD患者的肠道真菌变化。本研究发现，CKD患者的肠道真菌群落多样性和构成发生了显著的改变，进一步验证了肠道真菌可能成为CKD临床诊疗的新目标。Candida是人类肠道最常见的真菌属之一，而白色念珠菌是该异质性真菌属中最典型的一员［25］。值得注意的是，在包括炎症性肠病、艰难梭菌感染、肝病、哮喘以及精神分裂症等多种疾病中［19-24］，都观察到肠道白色念珠菌的丰度异常升高。这种真菌的细胞壁成分甘露聚糖能够激活CX3CR1+单核巨噬细胞的模式识别受体，触发信号转导级联反应，以脾脏酪氨酸激酶（spleen tyrosine kinase，SYK）信号依赖的方式驱动T辅助细胞17（T-helper-17，Th17）介导的肠道免疫反应［26-27］。此外，肠道中白色念珠菌的丰度增加还可减少肠道微环境的溶解氧，促进包括艰难梭菌在内的厌氧菌的生长，抑制共生乳杆菌的生长，从而扰乱肠道细菌微生物群的平衡［28-29］。本研究发现CKD患者的肠道真菌菌群中Candida的丰度明显增加。这种变化能够引起肠道稳态系统紊乱，包括微生物群、局部免疫和代谢等多个方面，进而导致肠屏障破坏。肠屏障的破坏使得内毒素和尿毒素等肠道微生物群的代谢物以及过度激活的炎症细胞、细胞因子和可溶性尿激酶纤溶酶原激活物表面受体（soluble urokinase plasminogen activator surface receptor，suPAR）等能够通过循环系统流入肾脏，可能进一步加重CKD进展［30］。因此，可以考虑将调节肠道真菌、恢复肠道微生物稳态作为CKD治疗的新策略，以提高CKD的治疗效果。
本研究探讨CKD患者肠道中真菌组成结构的变化特点，发现CKD患者的肠道真菌菌群存在明显失调。调节肠道真菌、恢复肠道微生物稳态可能成为CKD治疗的一种新思路。尽管如此，由于本研究纳入的病例数较少，仅局限于观察性研究，表明患有CKD的患者肠道真菌多样性和构成发生了变化，尚不能证明因果关系，存在一定局限性。需要进一步研究CKD患者肠道的真菌多样性、构成变化的潜在机制，以及真菌对CKD的具体作用机制。

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2025年第47卷第2期
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doi: 10.16016/j.2097-0927.202404133
  • 接收时间：2024-04-28
  • 首发时间：2026-10-30
  • 出版时间：2025-01-30
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  • 收稿日期：2024-04-28
  • 修回日期：2024-09-18
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    1陆军军医大学（第三军医大学）第二附属医院 普通外科，重庆
    2陆军军医大学（第三军医大学）第二附属医院 营养科，重庆

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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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