痛风患者肠道真菌特征及其临床相关性研究  

Characteristics of gut mycobiome in gout patients and their clinical correlation

作　　者：戈宇松 张春林 杜蓥漩 郭小芹 雷媛媛 侯占杰 冉雷 徐静 杨仕明 GE Yusong;ZHANG Chunlin;DU Yinxuan;GUO Xiaoqin;LEI Yuanyuan;HOU Zhanjie;RAN Lei;XU Jing;YANG Shiming(Department of Gastroenterology,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,China;Department of Endocrinology,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,China)

机构地区：[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)第二附属医院内分泌科,重庆

出　　处：《陆军军医大学学报》2025年第8期858-869,共12页Journal of Army Medical University

基　　金：重庆市自然科学基金(CSTB2022NSCQ-MSX1169)。

摘　　要：目的 通过内部转录间隔区1(internal transcribed spacer 1,ITS1)DNA高通量测序,比较痛风患者与健康人群之间肠道真菌组成情况。方法 以2023年1月至2024年12月期间,在陆军军医大学第二附属医院就诊的痛风患者及健康志愿者为研究对象。将痛风患者按照指南分为3个不同的疾病组,其中无症状高尿酸血症患者为H组,急性痛风性关节炎患者为G组,痛风性关节炎发作间歇期患者为I组,健康人群为N组,收集被研究人群的大便标本行ITS1测序分析,比较4组间肠道菌群多样性、组成结构及Guild功能营养状态的差别,并对肠道真菌与受试人群的临床指标进行相关性分析。结果 健康人群及痛风各组人群在性别、年龄、肾小球滤过率、血清肌酐、血清尿素氮等基线资料上均无统计学差异,但BMI、C反应蛋白、血清尿酸、血沉、血清白细胞介素1β、血清白细胞介素6有统计学差异(P<0.05)。根据ITS1分析,健康人群和痛风各组人群相比,α多样性及β多样性中的主坐标分析(PCoA)无统计学差异,但是随着痛风疾病进展,β多样性指数差异分析显示有统计学差异(P<0.05)。在真菌结构组成上,子囊菌门(Ascomycota)、担子菌门(Basidiomycota)、毛霉门(Mucoromycota)是全部分组中的优势菌门。相较于其他3组,N组毕赤酵母属(Pichia)明显增多(P<0.05),H组酿酒酵母属(Saccharomyces)明显增多(P<0.05),而G组斯塔莫酵母属(Starmerella)明显增多(P<0.05)。肠道真菌与临床指标相关性分析发现,Starmerella的相对丰度与IL-1β(P<0.01)、IL-6(P<0.05)显著正相关。Pichia的相对丰度与血清尿素氮呈负相关(P<0.05)。而Saccharomyces的相对丰度与IL-1β、IL-6显著负相关(P<0.05)。结论 痛风不同阶段患者肠道真菌的多样性及组成结构均会发生显著改变,Starmerella、Saccharomyces、Pichia等相对丰度的变化可能与患者多项临床指标相关。Objective To compare the gut fungal composition between gout patients and healthy individuals through high-throughput sequencing of ribosomal DNA internal transcribed spacer 1(ITS1).Methods Gout patients and healthy volunteers who visited our hospital from January 2023 to December 2024 were enrolled in this study.Then based on established medical guidelines,the gout patients were categorized into 3 groups:Group H(asymptomatic hyperuricemia,n=14),Group G(acute gouty arthritis,n=14),and Group I(intercritical period of gouty arthritis,n=15),and the healthy individuals were assigned into Group N(n=9).Fecal samples were collected from all the participants to undergo ITS1 sequencing analysis.The differences in diversity and composition of gut mycobiome,and FunGuild-derived fungal functions and nutritional status were compared among the 4 groups,and the correlation between the gut mycobiome and clinical indicators was analyzed.Results There were no significant differences in baseline features such as gender,age,glomerular filtration rate(GFR),and levels of serum creatinine(SCr)and serum urea among Group N and other gout groups,but obvious differences were observed in body mass index(BMI),erythrocyte sedimentation rate,and levels of C-reactive protein(CRP),serum uric acid(SUA),and IL-1βand IL-6(P<0.05).In terms of gut fungal diversity,ITS1 analysis showed there were no statistical differences inα-diversity or the principal coordinate analysis(PCoA)ofβ-diversity among the groups.However,as gout progressed,significant changes were observed inβ-diversity indices,indicating a shift in the gut fungal community composition with disease advancement(P<0.05).The phyla Ascomycota,Basidiomycota,and Mucoromycotina were the dominant fungal phyla in all groups.Compared with the other 3 gout groups,the abundance of Pichia was significantly increased in Group N(P<0.05),that of Saccharomyces was in Group H(P<0.05),and that of Starmerella was in Group G(P<0.05).Correlation analysis between the gut mycobiome and clinical indices indica

关 键 词：痛风 肠道真菌 斯塔莫酵母属 酿酒酵母属 毕赤酵母属 

分 类 号：Q939.5[生物学—微生物学] R322.45[医药卫生—人体解剖和组织胚胎学] R589.7[医药卫生—基础医学]