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摘要：
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摘要：目的 观察酒精性脂肪性肝病（alcohol related fatty liver disease，AFLD）患
者肠道菌群的变化特征。方法 选择2019年12月至2020年12月在首都医科大学附属
北京地坛医院就诊的AFLD患者为AFLD组（26例），选择性别、年龄等相匹配的
健康人群作为健康对照组（32例）。收集研究对象的身高、体质量、生活习惯和生
活地区等人口学信息；同时收集血液和粪便标本，检测丙氨酸氨基转移酶（alanine
aminotransferase，ALT）、天门冬氨酸氨基转氨酶（aspartate aminotransferase，
AST）、碱性磷酸酶（alkaline phosphatase，ALP）、γ-谷氨酰转肽酶（γ-glutamyl
transpeptadase，GGT）、血清总胆红素（total bilirubin，TBil）、肌酐（creatinine，
Cr）、总胆固醇（total cholesterol，TCHO）等临床指标和粪便菌群组成，并用α多
样性分析、主坐标分析和LEfSe分析方法等分析AFLD患者肠道菌群特征及其临床意
义。结果 α多样性分析显示，AFLD组和健康对照组肠道菌群丰度和多样性相似。
基于加权距离和非加权距离的主坐标分析中，AFLD组和健康对照组的肠道菌群结
构存在显著差异。AFLD组肠道菌群组成与健康对照组相比，门水平上，厚壁菌门
（Firmicutes）、变形菌门（Proteobacteria）和梭杆菌门（Fusobacteriota）相对丰度
升高，拟杆菌门（Bacteroidetes）和放线菌门（Actinobacteria）相对丰度降低；属水
平上，AFLD组大肠志贺菌属（Escherichia Shigella）、巨单胞菌属（Megamonas）、
梭杆菌属（Fusobacterium）、小类杆菌属（Dialister）、Lachnoclostridium、乳
杆菌属（Lactobacillus）、Tyzzerella、链球菌属（Streptococcus）、UCG-002和
Romboutsia相对丰度较健康对照组显著升高，普雷沃氏菌属（Prevotella）、拟杆菌属
（Bacteroides）、双歧杆菌属（Bifidobacterium）、粪杆菌属（Faecalibacterium）、布
劳特氏菌属（Blautia）、毛螺菌属（Lachnospira）、罗斯氏菌属（Roseburia）和瘤胃
球菌属（Ruminococcus）相对丰度降低。LEfSe分析发现AFLD组和健康对照组有6个
显著差异的菌属，AFLD组的梭杆菌属（Fusobacterium）、Lachnoclostridium和大肠志
贺菌属（Escherichia Shigella）数量显著增多，拟杆菌属（Bacteroides）、普雷沃氏菌
属（Prevotella）和粪杆菌属（Faecalibacterium）数量显著降低，差异均有统计学意义
（LDA ＞ 4，P ＜ 0.05）。其中，相对丰度降低的瘤胃球菌属和拟杆菌属以及相对丰
度增加的链球菌属用来诊断AFLD的受试者工作特征（receiver operator characteristic，
ROC）曲线下面积分别为0.817、0.757和0.820，提示它们可能作为区分健康对照和
AFLD的微生物学标志物。结论 AFLD患者肠道菌群结构较健康人群存在显著差异，与
AFLD密切相关的瘤胃球菌属和拟杆菌属降低及链球菌属的增加可能作为酒精性肝病早
期诊断的生物标志物。
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Abstract: Objective To investigate the changes of intestinal microbiota in patients with
alcohol related fatty liver disease (AFLD). Methods Patients with AFLD in Beijing Ditan
Hospital, Capital Medical University from December 2019 to December 2020 were selected
as AFLD group (26 cases), and healthy people matched with gender and age were selected
as healthy control group (32 cases). Demographic information such as height and weight
of subjects were collected. At the same time, blood and stool samples, living habits and
living areas were collected to detect the clinical indicators [alanine aminotransferase (ALT),
aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptadase
(GGT) total bilirubin (TBil), creatinine (Cr), total cholesterol (TCHO)] of hematology and the
composition of intestinal microbiota. The characteristics of intestinal microbiota in patients
with AFLD and its relationship with clinical indicators were analyzed by alpha diversity
analysis, principal coordinate analysis and LEfSe analysis. Results Alpha diversity analysis
showed that the abundance and diversity of intestinal microbiota in AFLD group and healthy
control group were similar. In the principal coordinate analysis (PCoA) based on weighted
UniFrac distance and unweighted UniFrac distance, there were significant differences in
the structure of intestinal microbiota between AFLD group and healthy control group. The
structure of intestinal microbiota in AFLD group has changed. Compared with healthy control
group, the relative abundance of Firmicutes, Proteobacteria and Fusobacteriota increased,
while the relative abundance of Bacteroidetes and Actinobacteria decreased. At the genus
level, the relative abundances of Escherichia Shigella, Megamonas, Fusobacterium, Dialist,
Lachnoclostridium, Lactobacillus, Tyzzerella, Streptococcus, UCG-002 and Romboutsia
in AFLD group were significantly higher than those in healthy control group. The relative
abundance of Prevotella, Bacteroides, Bifidobacterium, Faecalibacterium, Blautia,
Lachnospira, Roseburia and Ruminococcus decreased. LEfSe analysis showed that there
were 6 bacterial genera with significant differences between AFLD group and healthy control
group. The number of Fusobacterium, Lachnoclostridium and Escherichia Shigella in AFLD
group increased significantly, and the number of Bacteroides, Prevotella and Faecalibacterium
decreased significantly, and the difference was statistically significant (LDA ＞ 4, P ＜
0.055). Among them, the area under the receiver operator characteristic (ROC) curve of
Ruminococcus and Bacteroidetes with decreased relative abundance and Streptococcus with
increased relative abundance were 0.832, 0.768 and 0.823, respectively, suggesting that they
may be used as microbial markers to distinguish healthy control from AFLD. Conclusions
There are significant differences in the structure of intestinal microbiota in patients with
AFLD. The decreased Ruminococcus and Bacteroidetes and increased Streptococcus, which
closely associated with AFLD, may be served as biomarkers for the early diagnosis of ALD.
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