粪便微生物组可区分酒精摄入与酒精性肝炎，但无法区分疾病严重程度。
Fecal Microbiome Distinguishes Alcohol Consumption From Alcoholic Hepatitis But Does Not Discriminate Disease Severity.
机构信息
Department of Biostatistics, Virginia Commonwealth University, Richmond, VA.
Divison of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA.
出版信息
Hepatology. 2020 Jul;72(1):271-286. doi: 10.1002/hep.31178.
BACKGROUND AND AIMS
The role of the intestinal microbiome in alcoholic hepatitis is not established. The aims of this study were to (1) characterize the fecal microbial ecology associated with alcoholic hepatitis, (2) relate microbiome changes to disease severity, and (3) infer the functional relevance of shifts in microbial ecology.
APPROACH AND RESULTS
The fecal microbiome in patients with moderate alcoholic hepatitis (MAH) or severe alcoholic hepatitis (SAH) was compared with healthy controls (HCs) and heavy drinking controls (HDCs). Microbial taxa were identified by 16S pyrosequencing. Functional metagenomics was performed using PICRUSt. Fecal short chain fatty acids (SCFAs) were measured using a liquid chromatography-mass spectrometry platform. A total of 78 participants (HC, n = 24; HDC, n = 20; MAH, n = 10; SAH, n = 24) were studied. HDC had a distinct signature compared with HC with depletion of Bacteroidetes (46% vs. 26%; P = 0.01). Alcoholic hepatitis was associated with a distinct microbiome signature compared with HDC (area under the curve = 0.826); differential abundance of Ruminococcaceae, Veillonellaceae, Lachnospiraceae, Porphyromonadaceae, and Rikenellaceae families were the key contributors to these differences. The beta diversity was significantly different among the groups (permutational multivariate analysis of variance [PERMANOVA] P < 0.001). SAH was associated with increased Proteobacteria (SAH 14% vs. HDC 7% and SAH vs. HC 2%, P = 0.20 and 0.01, respectively). Firmicutes abundance declined from HDC to MAH to SAH (63% vs. 53% vs. 48%, respectively; P = 0.09, HDC vs. SAH). Microbial taxa did not distinguish between MAH and SAH (PERMANOVA P = 0.785). SCFAs producing bacteria (Lachnospiraceae and Ruminococcaceae) were decreased in alcoholic hepatitis, and a similar decrease was observed in fecal SCFAs among alcoholic hepatitis patients.
CONCLUSIONS
There are distinct changes in fecal microbiome associated with the development, but not severity, of alcoholic hepatitis.
背景与目的
肠道微生物群在酒精性肝炎中的作用尚未确定。本研究的目的是：(1) 描述与酒精性肝炎相关的粪便微生物生态；(2) 将微生物组变化与疾病严重程度相关联；(3) 推断微生物生态变化的功能相关性。
方法与结果
将中度酒精性肝炎（MAH）或严重酒精性肝炎（SAH）患者的粪便微生物组与健康对照（HC）和重度饮酒对照（HDC）进行比较。通过 16S 焦磷酸测序鉴定微生物分类群。使用 PICRUSt 进行功能宏基因组学分析。使用液相色谱-质谱联用平台测量粪便短链脂肪酸（SCFA）。共纳入 78 名参与者（HC：n=24；HDC：n=20；MAH：n=10；SAH：n=24）进行研究。与 HC 相比，HDC 的拟杆菌门（46%比 26%；P=0.01）明显减少。与 HDC 相比，酒精性肝炎患者的微生物组特征明显不同（曲线下面积=0.826）；粪便罗氏菌科、韦荣球菌科、毛螺菌科、卟啉单胞菌科和理研菌科的丰度差异是导致这些差异的关键因素。组间的 beta 多样性差异显著（置换多元方差分析[PERMANOVA]P<0.001）。与 HDC 相比，SAH 患者的变形菌门增加（SAH 为 14%，而 HDC 为 7%，SAH 与 HC 相比为 2%，P=0.20 和 0.01）。从 HDC 到 MAH 再到 SAH，厚壁菌门的丰度下降（分别为 63%、53%和 48%；P=0.09，HDC 与 SAH 相比）。微生物分类群不能区分 MAH 和 SAH（PERMANOVA P=0.785）。在酒精性肝炎患者中，产生 SCFA 的细菌（毛螺菌科和罗氏菌科）减少，粪便 SCFA 也出现类似减少。
结论
与酒精性肝炎的发生相关，但与严重程度无关，粪便微生物组存在明显变化。
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