Signature pathogenic bacteria in tongue coating drive the progression of chronic hepatitis B complicated with fatty liver disease <italic style="font-style: italic">via</italic> the “Oral-gut-liver axis” by regulating glucose and lipid metabolism

ZHAO Qing; CHEN Xinju; ZHANG Lihui; LIU Sutong; SHANG Dongfang; ZHANG Qiang; ZHAO Wenxia

doi:10.16016/j.2097-0927.202510035

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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

Clinical Medicine | 更新时间：2026-02-04

- 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
- Journal of Army Medical University Vol. 48, Issue 2, Pages: 169-180(2026)
- 作者机构：
  
  河南中医药大学第一附属医院消化科，河南郑州
- 作者简介：
  
  ZHAO Wenxia，E-mail：zhao-wenxia@163.com
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(82205086);the Construction Project of National Famous Traditional Chinese Medicine Expert Inheritance Studio(国中医药办人教函（2022）245号);the Special Project of Scientific Research on Traditional Chinese Medicine of Henan Province(2022JDZX031;2023ZXZX1092)
- DOI：10.16016/j.2097-0927.202510035
  CLC： R372;R512.62;R575.5
- Received：15 October 2025，
  
  Revised：2025-12-30，
  
  Accepted：30 December 2025，
  
  Published：30 January 2026
- 稿件说明：
移动端阅览
赵晴，陈欣菊，张丽慧，等.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［J］.陆军军医大学学报，2026，48（02）：169-180.DOI：10.16016/j.2097-0927.202510035.

ZHAO Q，CHEN X J，ZHANG L H，et al.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［J］.J Army Med Univ，2026，48（02）：169-180.DOI：10.16016/j.2097-0927.202510035.
赵晴，陈欣菊，张丽慧，等.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［J］.陆军军医大学学报，2026，48（02）：169-180.DOI：10.16016/j.2097-0927.202510035. DOI：

ZHAO Q，CHEN X J，ZHANG L H，et al.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［J］.J Army Med Univ，2026，48（02）：169-180.DOI：10.16016/j.2097-0927.202510035. DOI：

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（

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。

Abstract

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 micro

bial 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

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) (

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.

关键词

Keywords

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DOI：10.16016/j.2097-0927.202510035

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