The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis.
The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis.
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DOI：
10.1002/hep.29623
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
TREAT Consortium
中科院分区：
文献类型：
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作者：
Puri P;Liangpunsakul S;Christensen JE;Shah VH;Kamath PS;Gores GJ;Walker S;Comerford M;Katz B;Borst A;Yu Q;Kumar DP;Mirshahi F;Radaeva S;Chalasani NP;Crabb DW;Sanyal AJ;TREAT Consortium
肠道生物失调与酒精性肝炎(AH)有关。然而，循环微生物群的变化，它与AH的存在和严重程度的关系以及它在AH中的功能相关性尚不清楚。通过对18例中度或19例重度急性肝炎患者的细菌DNA测序，对循环微生物组的变化进行定性和定量的评估。将这些数据与无明显肝病的大量饮酒对照组(HDC)(n=19)和非饮酒对照组(NAC，n=20)进行比较。这些数据与内毒素水平和单核细胞活化标志物有关。进行线性判别分析(LDA)效应大小(LFSE)分析、推断的元基因组学和PICRUST的预测功能分析。MAH(P<；0.01)和SAH(P<；0.001)患者的16S拷贝数/ngDNA均显著增加。与NAC相比，HDC、MAH和SAH中类杆菌的相对丰度显著降低(p<；0.001)。相反，所有饮酒组都富含梭杆菌；这对HDC的影响最大，而对MAH和SAH的影响逐渐降低。SAH患者的内毒素血症显著升高(P=0.01)。与饮酒组相比，预测性功能元基因组学表明，细菌中富含与产甲烷和反硝化相关的基因。此外，HDC和SAH都显示出III型分泌系统的激活，这与革兰氏阴性细菌的毒力有关。SAH和NAC的宏基因组学预测，通过甲戊酸盐和邻氨基苯甲酸酯的降解，类异戊二烯的合成增加，这两种已知的调节剂分别是革兰氏阳性细菌生长和生物被膜产生的调节因子。总之，大量饮酒似乎是循环微生物群变化的主要驱动力，这些微生物群与其推测的代谢功能的变化有关。
Intestinal dysbiosis is implicated in alcoholic hepatitis (AH). However, changes in the circulating microbiome, its association with the presence and severity of AH and its functional relevance in AH is unknown. Qualitative and quantitative assessment of changes in the circulating microbiome were performed by sequencing bacterial DNA in subjects with moderate (n=18) or severe AH (n=19). These data were compared to heavy drinking controls (HDC) without obvious liver disease (n=19) and non-alcohol consuming controls (NAC, n=20). The data were related to endotoxin levels and markers of monocyte activation. Linear Discriminant Analysis (LDA) Effect Size (LEfSe) analysis, inferred metagenomics and predictive functional analysis using PICRUSt were performed. There was a significant increase in 16S copies/ng DNA both in MAH (p<0.01) and SAH (p<0.001) subjects. Compared to NAC, the relative abundance of phylum Bacteroidetes was significantly decreased in HDC, MAH, and SAH (p<0.001). In contrast, all alcohol consuming groups had enrichment with Fusobacteria; this was greatest for HDC and decreased progressively in MAH and SAH. Subjects with SAH had significantly higher endotoxemia (p=0.01). Compared to alcohol consuming groups, predictive functional metagenomics indicated an enrichment of bacteria with genes related to methanogenesis and denitrification. Also, both HDC and SAH showed activation of type III secretion system which has been linked to gram negative bacterial virulence. Metagenomics in SAH vs NAC predicted increased isoprenoid synthesis via mevalonate and anthranilate degradation, known modulators of gram positive bacterial growth and biofilm production respectively. In conclusion, heavy alcohol consumption appears to be the primary driver of changes in the circulating microbiome associated with a shift in its inferred metabolic functions.