To understand the pathophysiological impact of liver microbiota on the early stages of fibrosis we identified the corresponding microbiota sequences and overcome the impact of different group size and patient origins with adapted statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2) were collected from Romania(n=36), Austria(n=10), Italy(n=19), and Spain(n=17). The 16SrDNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences. Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50 % of liver taxa were Enterobacteriaceae and Pseudomonadaceae. The Caulobacteraceae, Flavobacteriaceae and Propionibacteriaceae discriminated between F0 and F1. The preQ0 biosynthesis and pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0. Altogether, our results suggest a role of bacterial translocation to the liver in the progression of fibrosis. This statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses.

中文翻译：

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肝纤维化初期人肝菌群建模策略

为了了解肝菌群对纤维化早期阶段的病理生理影响，我们鉴定了相应的菌群序列，并采用适应性统计方法克服了不同组别和患者来源的影响。从罗马尼亚（n = 36），奥地利（n = 10），意大利（n = 19）和西班牙（n = 17）收集了肝纤维化评分较低的肝样本（F0，F1，F2）。对16SrDNA基因进行了测序。我们考虑了人群之间的频率，稀疏性，不平衡的样本量，以识别分类特征和统计差异。多元分析，包括采用L1-惩罚公平判别策略进行的光谱聚类，以及预测的宏基因组学，用于鉴定50％的肝类群是肠杆菌科和假单胞菌科。棒杆菌科 黄杆菌科和丙酸杆菌科区分F0和F1。preQ0的生物合成和涉及葡萄糖基糖和糖原降解的途径与肝纤维化F1-F2与F0呈负相关。总而言之，我们的结果表明细菌在肝纤维化进展中易位至肝脏。这种统计方法可以识别微生物特征，并克服有关样本量差异，环境影响和分析集的问题。