Fecal Microbiome Distinguishes Alcohol Consumption From Alcoholic Hepatitis But Does Not Discriminate Disease Severity

毛螺菌科 酒精性肝炎 厚壁菌 拟杆菌 微生物群 粪便 酒精性肝病 医学 基因组 胃肠病学 内科学 蛋白质细菌 动物 生物 生物信息学 微生物学 细菌 遗传学 肝硬化 16S核糖体RNA 生物化学 基因
作者
Ekaterina Smirnova,Puneet Puri,Mark Muthiah,Kalyani Daitya,Robert S. Brown,Naga Chalasani,Suthat Liangpunsakul,Vijay H. Shah,Kayla Gelow,M. Shadab Siddiqui,Sherry Boyett,Faridoddin Mirshahi,Masoumeh Sikaroodi,Patrick M. Gillevet,Arun J. Sanyal
出处
期刊:Hepatology [Lippincott Williams & Wilkins]
卷期号:72 (1): 271-286 被引量:94
标识
DOI:10.1002/hep.31178
摘要

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.
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