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

被引:96
作者
Smirnova, Ekaterina [1 ]
Puri, Puneet [2 ]
Muthiah, Mark D. [3 ,4 ]
Daitya, Kalyani [2 ]
Brown, Robert [5 ]
Chalasani, Naga [6 ]
Liangpunsakul, Suthat [6 ]
Shah, Vijay H. [7 ]
Gelow, Kayla [8 ]
Siddiqui, Mohammed S. [2 ]
Boyett, Sherry [2 ]
Mirshahi, Faridoddin [2 ]
Sikaroodi, Masoumeh [5 ]
Gillevet, Patrick [5 ]
Sanyal, Arun J. [2 ]
机构
[1] Virginia Commonwealth Univ, Dept Biostat, Box 980032, Richmond, VA 23298 USA
[2] Virginia Commonwealth Univ, Dept Internal Med, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA
[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore
[4] Natl Univ Singapore Hosp, Div Gastroenterol & Hepatol, Singapore, Singapore
[5] George Mason Univ, Dept Microbiol, Manassas, VA USA
[6] Indiana Univ, Dept Internal Med, Div Gastroenterol, Indianapolis, IN 46204 USA
[7] Mayo Clin, Div Gastroenterol, Dept Internal Med, Rochester, MN USA
[8] Indiana Univ, Dept Biostat, Indianapolis, IN 46204 USA
关键词
GUT MICROBIOTA; LIVER-DISEASE; MORTALITY;
D O I
10.1002/hep.31178
中图分类号
R57 [消化系及腹部疾病];
学科分类号
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 (PERMANOVAP = 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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收藏
页码:271 / 286
页数:16
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