多囊肾病患者肠道真菌特征性改变及其与临床指标的相关性研究

HOU Zhanjie; GE Yusong; TANG Bo; LEI Yuanyuan; TANG Li; JIANG Hongfei; JIAN Jincheng; CHENG Jinbo; YANG Shiming

doi:10.16016/j.2097-0927.202411111

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多囊肾病患者肠道真菌特征性改变及其与临床指标的相关性研究

Clinical Medicine | 更新时间：2025-04-25

- 多囊肾病患者肠道真菌特征性改变及其与临床指标的相关性研究
- Journal of Army Medical University Vol. 47, Issue 8, Pages: 836-846(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）第二附属医院：，消化内科，重庆
  2.陆军军医大学（第三军医大学）第二附属医院：，肾内科，重庆
- 作者简介：
  
  CHENG Jinbo， E-mail： Jinbo2008@163.com
  YANG Shiming， E-mail： yangshiming@tmmu.edu.cn
- 基金信息：
- DOI：10.16016/j.2097-0927.202411111
  CLC：
- Received：25 November 2024，
  
  Revised：08 March 2025，
  
  Published：30 April 2025
- 稿件说明：
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侯占杰,戈宇松,唐波,等.多囊肾病患者肠道真菌特征性改变及其与临床指标的相关性研究[J].陆军军医大学学报,2025,47(08):836-846.

HOU Zhanjie,GE Yusong,TANG Bo,et al.Changes in characteristics of gut fungal microbiota and their correlation with clinical indicators in patients with polycystic kidney disease[J].J Army Med Univ,2025,47(08):836-846.
侯占杰,戈宇松,唐波,等.多囊肾病患者肠道真菌特征性改变及其与临床指标的相关性研究[J].陆军军医大学学报,2025,47(08):836-846. DOI：10.16016/j.2097-0927.202411111.

HOU Zhanjie,GE Yusong,TANG Bo,et al.Changes in characteristics of gut fungal microbiota and their correlation with clinical indicators in patients with polycystic kidney disease[J].J Army Med Univ,2025,47(08):836-846. DOI：10.16016/j.2097-0927.202411111.

摘要

‍

目的

研究多囊肾病（polycystic kidney disease，PKD）患者肠道真菌菌群多样性、组成结构及其与临床指标的相关性。

方法

纳入2023年2月至2024年2月就诊于陆军军医大学第二附属医院的PKD患者44例、非多囊肾病慢性肾病（non-polycystic kidney disease chronic kidney disease，NPCKD）患者44例和健康对照者（health controls，HC）22例，基于ITS1 DNA测序技术分析受试者粪便样本肠道真菌组成，应用生物信息学方法比较各组间真菌的多样性和结构差异，并运用Pearson相关分析探讨肠道真菌与临床指标的相关性。

结果

3组基线资料（性别、年龄、体质量指数等）差异无统计学意义，血清学指标（血肌酐、尿素氮、尿酸、估算肾小球滤过率等）存在统计学差异（

0.01）。Alpha多样性分析显示，PKD组与HC组差异无统计学意义，与NPCKD组相比差异有统计学意义（

0.01）。Beta多样性分析表明，3组间比较及两两比较均有统计学差异（

0.001）。菌群结构分析发现，PKD组

Candida

（假丝酵母菌属）丰度显著高于其他2组（

0.01），而

Aspergillus

（曲霉菌属）、

Cladosporium

（枝孢菌属）丰度显著低于HC组（

0.05）。线性判别分析（LEFSe）表明PKD组中

Candida

显著富集，

Aspergillus

、

Cladosporium

显著减少。相关性分析显示，PKD组

Cladosporium

丰度与肾囊肿直径、免疫轻链Kappa/Lamda呈负相关（

0.05），而

Candida

丰度与肝/肾囊肿直径呈正相关（

0.01）。

结论

PKD患者肠道真菌菌群多样性和组成结构存在特征性改变，

Cladosporium

和

Candida

与PKD患者的临床指标密切相关。

Abstract

Objective‍　‍To investigate the diversity and composition of gut fungi microbiota in patients with polycystic kidney disease (PKD) and its correlat

ion with clinical indicators. Methods‍　‍A total of 44 PKD patients

44 patients with non-polycystic chronic kidney disease (NPCKD) and 22 healthy controls (HC) admitted to our hospital from February 2023 to February 2024 were recruited. ITS1 DNA sequencing was applied to analyze the gut fungal composition. Bioinformatics analysis was used to compare the diversity and structural differences of fungi among the 3 groups. Pearson correlation analysis was performed to analyze the relationship between gut fungi and clinical indicators. Results‍　‍There were no significant differences in baseline characteristics (gender

age

body mass index

etc.

) among the 3 groups

but statistical differences were seen in terms of serum indicators (such as serum creatinine

blood urea nitrogen

uric acid

estimated glomerular filtration rate

etc

.) (

0.01). Alpha diversity analysis showed no significant difference was seen between the PKD and HC groups

but the PKD group had significant differences to the NPCKD group (

0.01). Beta diversity analysis revealed significant differences among the 3 groups and in pairwise comparisons (

0.001). Fungi composition analysis found that the abundance of

Candida

was significantly higher in the PKD group than the other 2 groups (

0.01)

while the abundances of

Aspergillus

and

Cladosporium

were significantly lower in the PKD group than the HC group (

0.05). Linear discriminant analysis (LEFSe) indicated that

Candida

was significantly enriched

while

Aspergillus

and

Cladosporium

were significantly reduced in the PKD group. Correlation analysis revealed that the abundance of

Cladosporium

was negatively correlated with cyst diameter and immunoglobulin light chain Kappa/Lambda ratio in the PKD group (

0.05)

while the abundance of

Candida

was positively correlated with liver/kidney cyst diameter (

0.01). Conclusion‍　‍PKD patients exhibit characteristic changes in gut fungi diversity and composition. The abundances of

Cladosporium

and

Candida

are closely associated with clinical indicators of PKD patients.

关键词

Keywords

references

WEBSTER A C ， NAGLER E V ， MORTON R L ， et al . Chronic kidney disease ［J］. Lancet ， 2017 ， 389 （ 10075 ）： 1238 - 1252 . DOI： 10.1016/s0140-6736（16）32064-5 http://dx.doi.org/10.1016/s0140-6736（16）32064-5 .

CHRONIC KIDNEY DISEASE COLLABORATION G B D . Global， regional， and national burden of chronic kidney disease， 1990-2017： a systematic analysis for the Global Burden of Disease Study 2017 ［J］. Lancet ， 2020 ， 395 （ 10225 ）： 709 - 733 . DOI： 10.1016/S0140-6736（20）30045-3 http://dx.doi.org/10.1016/S0140-6736（20）30045-3 .

KALANTAR-ZADEH K ， JAFAR T H ， NITSCH D ， et al . Chronic kidney disease ［J］. Lancet ， 2021 ， 398 （ 10302 ）： 786 - 802 . DOI： 10.1016/s0140-6736（21）00519-5 http://dx.doi.org/10.1016/s0140-6736（21）00519-5 .

STEINMAN T I . Polycystic kidney disease： a new perspective from the beginning ［J］. Kidney Int ， 2005 ， 68 （ 5 ）： 2398 - 2399 . DOI： 10.1111/j.1523-1755.2005.00711.x http://dx.doi.org/10.1111/j.1523-1755.2005.00711.x .

HOU X Y ， MRUG M ， YODER B K ， et al . Cystin， a novel Cilia -associated protein， is disrupted in the cpk mouse model of polycystic kidney disease ［J］. J Clin Invest ， 2002 ， 109 （ 4 ）： 533 - 540 . DOI： 10.1172/jci0214099 http://dx.doi.org/10.1172/jci0214099 .

MENEZES L F ， GERMINO G G . The pathobiology of polycystic kidney disease from a metabolic viewpoint ［J］. Nat Rev Nephrol ， 2019 ， 15 （ 12 ）： 735 - 749 . DOI： 10.1038/s41581-019-0183-y http://dx.doi.org/10.1038/s41581-019-0183-y .

TORRES V E ， HARRIS P C ， PIRSON Y . Autosomal dominant polycystic kidney disease ［J］. Lancet ， 2007 ， 369 （ 9569 ）： 1287 - 1301 . DOI： 10.1016/S0140-6736（07）60601-1 http://dx.doi.org/10.1016/S0140-6736（07）60601-1 .

CORNEC-LE GALL E ， ALAM A ， PERRONE R D . Autosomal dominant polycystic kidney disease ［J］. Lancet ， 2019 ， 393 （ 10174 ）： 919 - 935 . DOI： 10.1016/s0140-6736（18）32782-x http://dx.doi.org/10.1016/s0140-6736（18）32782-x .

BAE K T ， ZHU F ， CHAPMAN A B ， et al . Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease： the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort ［J］. Clin J Am Soc Nephrol ， 2006 ， 1 （ 1 ）： 64 - 69 . DOI： 10.2215/cjn.00080605 http://dx.doi.org/10.2215/cjn.00080605 .

PAUL B M ， VANDEN HEUVEL G B . Kidney： polycystic kidney disease ［J］. Wires Dev Biol ， 2014 ， 3 （ 6 ）： 465 - 487 . DOI： 10.1002/wdev.152 http://dx.doi.org/10.1002/wdev.152 .

NAKASHIMA M ， SUGA N ， IKEDA Y ， et al . Inspiring tactics with the improvement of mitophagy and redox balance for the development of innovative treatment against polycystic kidney disease ［J］. Biomolecules ， 2024 ， 14 （ 2 ）： 207 . DOI： 10.3390/biom14020207 http://dx.doi.org/10.3390/biom14020207 .

YANG T ， RICHARDS E M ， PEPINE C J ， et al . The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease ［J］. Nat Rev Nephrol ， 2018 ， 14 （ 7 ）： 442 - 456 . DOI： 10.1038/s41581-018-0018-2 http://dx.doi.org/10.1038/s41581-018-0018-2 .

李莉莎，熊大迁 . 肠道细菌 Phascolarctobacterium / Phascolarctobacterium faecium与2型糖尿病中代谢紊乱的关联分析［J］. 陆军军医大学学报， 2024 ， 46 （ 13 ）： 1561 - 1568 . DOI： 10.16016/j.2097-0927.202310036 http://dx.doi.org/10.16016/j.2097-0927.202310036 .

LI L S ， XIONG D Q . Correlation between intestinal bacteria Phascolarctobacterium / Phascolarctobacterium faecium and metabolic disorder in patients with type 2 diabetes mellitus ［J］. J Army Med Univ ， 2024 ， 46 （ 13 ）： 1561 - 1568 . DOI： 10.16016/j.2097-0927.202310036 http://dx.doi.org/10.16016/j.2097-0927.202310036 .

NORIAKI S ， MASANORI K ， TAKANORI H ， et al . Metagenomic profiling of gut microbiome in early chronic kidney disease ［J］. Nephrol Dial Transplant ， 2020 ， 36 （ 9 ）： 1675 - 1684 .

KIM S M ， SONG I H . The clinical impact of gut microbiota in chronic kidney disease ［J］. Korean J Intern Med ， 2020 ， 35 （ 6 ）： 1305 - 1316 . DOI： 10.3904/kjim.2020.411 http://dx.doi.org/10.3904/kjim.2020.411 .

YACOUB R ， NADKARNI G N ， MCSKIMMING D I ， et al . Fecal microbiota analysis of polycystic kidney disease patients according to renal function： a pilot study ［J］. Exp Biol Med （Maywood）， 2019 ， 244 （ 6 ）： 505 - 513 . DOI： 10.1177/1535370218818175 http://dx.doi.org/10.1177/1535370218818175 .

谢会超，肖卫东，韩奔，等 . 慢性肾脏病患者肠道真菌多样性及构成改变［J］. 陆军军医大学学报， 2025 ， 47 （ 2 ）： 168 - 176 . DOI： 10.16016/j.2097-0927.202404133 http://dx.doi.org/10.16016/j.2097-0927.202404133 .

XIE H C ， XIAO W D ， HAN B ， et al . Diversity and composition changes of intestinal fungi in patients with chronic kidney disease ［J］. J Army Med Univ ， 2025 ， 47 （ 2 ）： 168 - 176 . DOI： 10.16016/j.2097-0927.202404133 http://dx.doi.org/10.16016/j.2097-0927.202404133 .

HU J L ， WEI S C ， GU Y F ， et al . Gut mycobiome in patients with chronic kidney disease was altered and associated with immunological profiles ［J］. Front Immunol ， 2022 ， 13 ： 843695 . DOI： 10.3389/fimmu.2022.843695 http://dx.doi.org/10.3389/fimmu.2022.843695 .

ZOU Y Q ， GE A X ， LYDIA B ， et al . Gut mycobiome dysbiosis contributes to the development of hypertension and its response to immunoglobulin light chains ［J］. Front Immunol ， 2022 ， 13 ： 1089295 . DOI： 10.3389/fimmu.2022.1089295 http://dx.doi.org/10.3389/fimmu.2022.1089295 .

ILIEV I D . Mycobiota-host immune interactions in IBD： coming out of the shadows ［J］. Nat Rev Gastroenterol Hepatol ， 2022 ， 19 （ 2 ）： 91 - 92 . DOI： 10.1038/s41575-021-00541-2 http://dx.doi.org/10.1038/s41575-021-00541-2 .

SOKOL H ， LEDUCQ V ， ASCHARD H ， et al . Fungal microbiota dysbiosis in IBD ［J］. Gut ， 2017 ， 66 （ 6 ）： 1039 - 1048 . DOI： 10.1136/gutjnl-2015-310746 http://dx.doi.org/10.1136/gutjnl-2015-310746 .

NELSON A ， STEWART C J ， KENNEDY N A ， et al . The impact of NOD2 genetic variants on the gut mycobiota in Crohn’s disease patients in remission and in individuals without gastrointestinal inflammation ［J］. J Crohns Colitis ， 2021 ， 15 （ 5 ）： 800 - 812 . DOI： 10.1093/ecco-jcc/jjaa220 http://dx.doi.org/10.1093/ecco-jcc/jjaa220 .

SHAH S ， LOCCA A ， DORSETT Y ， et al . Alterations of the gut mycobiome in patients with MS ［J］. EBioMedicine ， 2021 ， 71 ： 103557 . DOI： 10.1016/j.ebiom.2021.103557 http://dx.doi.org/10.1016/j.ebiom.2021.103557 .

BAJAJ J S ， LIU E J ， KHERADMAN R ， et al . Fungal dysbiosis in cirrhosis ［J］. Gut ， 2018 ， 67 （ 6 ）： 1146 - 1154 . DOI： 10.1136/gutjnl-2016-313170 http://dx.doi.org/10.1136/gutjnl-2016-313170 .

XIE Z Y ， BAI Y X ， CHEN G J ， et al . Immunomodulatory activity of polysaccharides from the Mycelium of Aspergillus cristatus ， isolated from Fuzhuan brick tea， associated with the regulation of intestinal barrier function and gut microbiota ［J］. Food Res Int ， 2022 ， 152 ： 110901 . DOI： 10.1016/j.foodres.2021.110901 http://dx.doi.org/10.1016/j.foodres.2021.110901 .

LIN Y F ， LAU H C ， LIU Y L ， et al . Altered mycobiota signatures and enriched pathogenic Aspergillus rambellii are associated with colorectal cancer based on multicohort fecal metagenomic analyses ［J］. Gastroenterology ， 2022 ， 163 （ 4 ）： 908 - 921 . DOI： 10.1053/j.gastro.2022.06.038 http://dx.doi.org/10.1053/j.gastro.2022.06.038 .

CIMICKÁ J ， RIEGERT J ， KAVKOVÁ M ， et al . Intestinal mycobiome associated with diagnosis of inflammatory bowel disease based on tissue biopsies ［J］. Med Mycol ， 2022 ， 60 （ 1 ）： myab076 . DOI： 10.1093/mmy/myab076 http://dx.doi.org/10.1093/mmy/myab076 .

YOU N ， XU J ， WANG L ， et al . Fecal fungi dysbiosis in nonalcoholic fatty liver disease ［J］. Obesity （Silver Spring）， 2021 ， 29 （ 2 ）： 350 - 358 . DOI： 10.1002/oby.23073 http://dx.doi.org/10.1002/oby.23073 .

CATALÁN-SERRA I ， THORSVIK S ， BEISVAG V ， et al . Fungal microbiota composition in inflammatory bowel disease patients： characterization in different phenotypes and correlation with clinical activity and disease course ［J］. Inflamm Bowel Dis ， 2024 ， 30 （ 7 ）： 1164 - 1177 . DOI： 10.1093/ibd/izad289 http://dx.doi.org/10.1093/ibd/izad289 .

FARSI D N ， NELSON A ， KOUTSIDIS G ， et al . A high-fungi diet differentially attenuates the gut mycobiota relative to a high meat diet； consequences for chronic disease risk？［J］. Proc Nutr Soc ， 2024 ， 83（OCE2）： E197. DOI： 10.1017/s002966512400421x http://dx.doi.org/10.1017/s002966512400421x .

QIU J ， ZHAO L Y ， CHENG Y W ， et al . Exploring the gut mycobiome： differential composition and clinical associations in hypertension， chronic kidney disease， and their comorbidity ［J］. Front Immunol ， 2023 ， 14 ： 1317809 . DOI： 10.3389/fimmu.2023.1317809 http://dx.doi.org/10.3389/fimmu.2023.1317809 .

KONG H H ， SEGRE J A . Cultivating fungal research ［J］. Science ， 2020 ， 368 （ 6489 ）： 365 - 366 . DOI： 10.1126/science.aaz8086 http://dx.doi.org/10.1126/science.aaz8086 .

LIMON J J ， SKALSKI J H ， UNDERHILL D M . Commensal fungi in health and disease ［J］. Cell Host Microbe ， 2017 ， 22 （ 2 ）： 156 - 165 . DOI： 10.1016/j.chom.2017.07.002 http://dx.doi.org/10.1016/j.chom.2017.07.002 .

OST K S ， O’MEARA T R ， ZAC STEPHENS W ， et al . Adaptive immunity induces mutualism between commensal eukaryotes ［J］. Nature ， 2021 ， 596 （ 7870 ）： 114 - 118 . DOI： 10.1038/s41586-021-03722-w http://dx.doi.org/10.1038/s41586-021-03722-w .

NOBILE C J ， JOHNSON A D . Candida albicans biofilms and human disease ［J］. Annu Rev Microbiol ， 2015 ， 69 ： 71 - 92 . DOI： 10.1146/annurev-micro-091014-104330 http://dx.doi.org/10.1146/annurev-micro-091014-104330 .

WANG X F ， YANG S T ， LI S H ， et al . Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents ［J］. Gut ， 2020 ， 69 （ 12 ）： 2131 - 2142 . DOI： 10.1136/gutjnl-2019-319766 http://dx.doi.org/10.1136/gutjnl-2019-319766 .

GAUTAM R ， MAAN P ， PATEL A K ， et al . Unveiling the complex interplay between gut microbiota and polycystic ovary syndrome： a narrative review ［J］. Clin Nutr ， 2024 ， 43 （ 12 ）： 199 - 208 . DOI： 10.1016/j.clnu.2024.10.028 http://dx.doi.org/10.1016/j.clnu.2024.10.028 .

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