首页|期刊导航|陆军军医大学学报|舌苔标志性致病菌通过"口-肠-肝轴"调控糖脂代谢驱动慢性乙型肝炎合并脂肪肝疾病进展

舌苔标志性致病菌通过"口-肠-肝轴"调控糖脂代谢驱动慢性乙型肝炎合并脂肪肝疾病进展OA

Signature pathogenic bacteria in tongue coating drive the progression of chronic hepatitis B complicated with fatty liver disease via the"Oral-gut-liver axis"by regulating glucose and lipid metabolism

中文摘要英文摘要

目的 通过比较健康人群、慢性乙型肝炎(chronic hepatitis B,CHB)患者、CHB合并非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)患者的舌苔菌群变化特点,探讨CHB合并NAFLD患者舌苔菌群特征及共病机制.方法 选取2024年1-12月就诊于河南中医药大学第一附属医院消化科的CHB合并NAFLD患者42例(CHB合并NAFLD组)、单纯CHB患者34例(单纯CHB组),另选取体检科同期体检的健康人群(健康对照组)28例作为对照.收集所有研究对象的基线临床资料并分析组间差异.留取舌苔标本,采用PacBio Sequel测序平台对其16S核糖体核糖核酸(16S ribosomal RNA,16S rRNA)基因进行测序,经序列质控、去噪及ASV聚类后,分析3组样本的菌群组成、α多样性与β多样性,利用线性判别分析效应大小(linear discriminant analysis effect size,LEfSe)分析筛选组间差异标志物种,并进行京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)及MetaCyc功能预测分析.结果 3组研究对象在年龄、性别、BMI、谷丙转氨酶、空腹血糖、游离脂肪酸的差异均具有统计学意义(P<0.05).共获得48 236个ASV,CHB合并NAFLD组独有ASV最多.与健康对照组相比,CHB合并NAFLD组舌苔菌群的物种丰富度、群落异质性及分布均匀度均呈上升趋势.在门水平上,CHB合并NAFLD组厚壁菌门(Firmicutes,32%)、变形菌门(Proteobacteria,26%)占比较健康对照组增加,拟杆菌门(Bacteroidota,27%)占比减少;与单纯CHB组相比,其Bacteroidota占比增加.在属水平上,CHB合并NAFLD组韦荣球菌属(Veillonella,18%)、奈瑟菌属(Neisseria,18%)占比较健康对照组增加,普雷沃菌属_7(Prevotella_7,15%)占比减少;与单纯CHB组相比,其Neisseria、Prevotella_7占比增加.LEfSe分析显示,放线菌门(Actinobacteriota)、长奈瑟菌(Neisseria_elongata)及口腔链球菌(Streptococcus_oralis)是CHB合并NAFLD组的潜在标志物种.KEGG与MetaCyc功能预测分析均提示,3组舌苔菌群的功能差异主要富集于辅因子与维生素代谢、糖代谢及脂质代谢等通路.结论 CHB合并NAFLD患者的舌苔菌群结构表现出特征性变化,其特定致病菌丰度增加可能通过"口-肠-肝轴"调控糖脂代谢,从而促进NAFLD的进程.

Objective To compare the characteristics of tongue coating flora in healthy people,patients with chronic hepatitis B(CHB)and patients with CHB complicated with non-alcoholic fatty liver disease(NAFLD),and to explore the characteristics of tongue coating flora in patients with CHB complicated with NAFLD and its comorbidity mechanism.Methods From January 2024 to December 2024,42 with CHB complicated with NAFLD patients with CHB complicated with NAFLD(CHB complicated with NAFLD group)and 34 patients with simple CHB(simple CHB group)were subjected in our department,and 28 healthy individuals were selected and served as control group.Baseline clinical data were collected from all the participants,and intergroup differences were analyzed.After tongue coating samples were harvested for 16S ribosomal RNA(16S rRNA)sequencing using the PacBio Sequel sequencing platform.After sequence quality control,denoising,and amplicon sequence variant(ASV)clustering,the microbial composition,α diversity,and β diversity were analyzed in the 3 sample groups.Linear discriminant analysis effect size(LEfSe)was used to screen for intergroup differential marker species,by linear discriminant analysis(LDA)score>2 and P<0.05,and Kyoto encyclopedia of genes and genomes(KEGG)and MetaCyc functional prediction analyses were also performed.Results Significant differences were observed among the 3 groups in terms of age,gender,body mass index(BMI),alanine aminotransferase(ALT),fasting plasma glucose(FPG)and free fatty acids(FFA)(P<0.05).There were totally 48 236 ASVs obtained,with CHB complicated with NAFLD group having the highest number of unique ASVs.Compared to the healthy control group,the CHB complicated with NAFLD group exhibited an increasing trend in species richness,community heterogeneity,and distribution uniformity of the tongue coating microbiota.At the phylum level,the proportions of Firmicutes(32%)and Proteobacteria(26%)were increased,while the proportion of Bacteroidota(27%)was decreased in the CHB complicated with NAFLD group than the healthy control group.In comparison to the CHB-only group,the proportion of Bacteroidota was increased.At the genus level,the proportions of Veillonella(18%)and Neisseria(18%)were increased,while that of Prevotella_7(15%)was decreased in the CHB complicated with NAFLD group than the healthy control group,and that of Neisseria and Prevotella_7 was increased in the CHB complicated with NAFLD group when compared with the CHB-only group.LEfSe analysis revealed that Actinobacteriota,Neisseria_elongata,and Streptococcus_oralis were potential marker species in the CHB complicated with NAFLD group.Both KEGG and MetaCyc functional prediction analyses indicated that the differentially expressed functions of the tongue coating microbiota among the 3 groups were primarily enriched in pathways such as cofactor and vitamin metabolism,carbohydrate metabolism,and lipid metabolism.Conclusion CHB complicated with NAFLD patients exhibit characteristic changes in their tongue coating microbiota.The flora of tongue coating may affect the glucose and lipid metabolism of CHB patients through the"Oral-gut-liver axis",and promote the process and progress of NAFLD.

赵晴;陈欣菊;张丽慧;刘素彤;尚东方;张强;赵文霞

河南中医药大学第一附属医院消化科,河南郑州河南中医药大学第一附属医院消化科,河南郑州河南中医药大学第一附属医院消化科,河南郑州河南中医药大学第一附属医院消化科,河南郑州河南中医药大学第一附属医院消化科,河南郑州河南中医药大学第一附属医院消化科,河南郑州河南中医药大学第一附属医院消化科,河南郑州

医药卫生

慢性乙型肝炎非酒精性脂肪性肝病共病微生物群

hepatitis B,chronicnon-alcoholic fatty liver diseasecomorbiditytonguemicrobiota

《陆军军医大学学报》 2026 (2)

169-180,12

国家自然科学基金青年科学基金项目(82205086)全国名中医传承工作室建设项目[国中医药办人教函(2022)245号]河南省中医药科学研究专项课题(2022JDZX031,2023ZXZX1092) Supported by the National Natural Science Foundation for Young Scholars of China(82205086),the Construction Project of National Famous Traditional Chinese Medicine Expert Inheritance Studio(2022-245),and the Special Project of Scientific Research on Traditional Chinese Medicine of Henan Province(2022JDZX031,2023ZXZX1092).

10.16016/j.2097-0927.202510035

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