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Abstract：
BACKGROUND: The pathogenesis of MASLD (metabolic dysfunction-associated steatotic liver disease), including its severe clinical forms, involves complex processes at all levels of biological organization. This study examined the potential link between the liver microbiome profile and epigenetic factors.
METHODS: Liver microbial DNA composition was analysed using high throughput 16S rRNA gene sequencing in 116 individuals, with 55% being female, across the spectrum of liver disease severity. Total activity of histone deacetylases (HDACs) and acetyltransferases (HATs) was assayed in nuclear extracts from fresh liver samples. In addition, we measured the global 5-hydroxymethylcytosine (5-hmC) levels of liver DNA.
RESULTS: Patients with MASLD showed a 2.07-fold increase (p = 0.013) in liver total HAT activity. Moreover, a correlation was observed between liver total HAT activity and the score for histological steatosis (Spearman\'s R = 0.60, p = 1.0E-3) and disease severity (R = 0.40, p = 2.0E-2). Liver HAT and HDAC activities also showed associations with the abundance of several liver bacterial DNAs. Additionally, liver global levels of 5-hmC showed negative correlation with the read number of Bacteroidetes (R = -0.62, p = 9.3E-4) and Gammaproteobacteria (R = -0.43, p = 3.2E-2), while it was positively correlated with the abundance of Acidobacteria (R = 0.42, p = 4.1E-2) and Actinobacteria (R = 0.47, p = 1.8E-2).
CONCLUSIONS: The host liver epigenome, including the activity of enzymes involved in maintaining the balance between protein acetylation and deacetylation and the global DNA hydroxy-methylation status, may be the target of microbial signals.
BACKGROUND: Agencia Nacional de Promoción Científica y Tecnológica, FonCyT.
METHODS: Liver microbial DNA composition was analysed using high throughput 16S rRNA gene sequencing in 116 individuals, with 55% being female, across the spectrum of liver disease severity. Total activity of histone deacetylases (HDACs) and acetyltransferases (HATs) was assayed in nuclear extracts from fresh liver samples. In addition, we measured the global 5-hydroxymethylcytosine (5-hmC) levels of liver DNA.
RESULTS: Patients with MASLD showed a 2.07-fold increase (p = 0.013) in liver total HAT activity. Moreover, a correlation was observed between liver total HAT activity and the score for histological steatosis (Spearman\'s R = 0.60, p = 1.0E-3) and disease severity (R = 0.40, p = 2.0E-2). Liver HAT and HDAC activities also showed associations with the abundance of several liver bacterial DNAs. Additionally, liver global levels of 5-hmC showed negative correlation with the read number of Bacteroidetes (R = -0.62, p = 9.3E-4) and Gammaproteobacteria (R = -0.43, p = 3.2E-2), while it was positively correlated with the abundance of Acidobacteria (R = 0.42, p = 4.1E-2) and Actinobacteria (R = 0.47, p = 1.8E-2).
CONCLUSIONS: The host liver epigenome, including the activity of enzymes involved in maintaining the balance between protein acetylation and deacetylation and the global DNA hydroxy-methylation status, may be the target of microbial signals.
BACKGROUND: Agencia Nacional de Promoción Científica y Tecnológica, FonCyT.
摘要：
背景：MASLD（代谢功能障碍相关的脂肪变性肝病）的发病机制，包括其严重的临床形式，涉及生物组织各个层面的复杂过程。这项研究检查了肝脏微生物组谱和表观遗传因素之间的潜在联系。
方法：使用高通量16SrRNA基因测序分析116个个体的肝脏微生物DNA组成，55%是女性，在肝脏疾病严重程度的范围内。在新鲜肝脏样品的核提取物中测定了组蛋白脱乙酰酶（HDAC）和乙酰转移酶（HAT）的总活性。此外,我们测量了肝脏DNA的总体5-羟甲基胞嘧啶（5-hmC）水平。
结果：MASLD患者肝脏总HAT活性增加2.07倍（p=0.013）。此外，肝脏总HAT活性与组织学脂肪变性评分(Spearman'sR=0.60,p=1.0E-3)和疾病严重程度(R=0.40,p=2.0E-2)之间存在相关性.肝脏HAT和HDAC活性也显示与多种肝脏细菌DNA的丰度相关。此外,5-hmC的肝脏整体水平与拟杆菌（R=-0.62，p=9.3E-4）和γ变形杆菌（R=-0.43，p=3.2E-2）的读数呈负相关，而与酸性细菌（R=0.42，p=4.1E-2）和放线菌（R=0.47，p=1.8E-2）的丰度呈正相关。
结论：宿主肝脏表观基因组，包括维持蛋白质乙酰化和去乙酰化之间的平衡以及全球DNA羟基甲基化状态的酶的活性，可能是微生物信号的目标。
背景：国家推广委员会和技术委员会，FonCyT.
方法：使用高通量16SrRNA基因测序分析116个个体的肝脏微生物DNA组成，55%是女性，在肝脏疾病严重程度的范围内。在新鲜肝脏样品的核提取物中测定了组蛋白脱乙酰酶（HDAC）和乙酰转移酶（HAT）的总活性。此外,我们测量了肝脏DNA的总体5-羟甲基胞嘧啶（5-hmC）水平。
结果：MASLD患者肝脏总HAT活性增加2.07倍（p=0.013）。此外，肝脏总HAT活性与组织学脂肪变性评分(Spearman'sR=0.60,p=1.0E-3)和疾病严重程度(R=0.40,p=2.0E-2)之间存在相关性.肝脏HAT和HDAC活性也显示与多种肝脏细菌DNA的丰度相关。此外,5-hmC的肝脏整体水平与拟杆菌（R=-0.62，p=9.3E-4）和γ变形杆菌（R=-0.43，p=3.2E-2）的读数呈负相关，而与酸性细菌（R=0.42，p=4.1E-2）和放线菌（R=0.47，p=1.8E-2）的丰度呈正相关。
结论：宿主肝脏表观基因组，包括维持蛋白质乙酰化和去乙酰化之间的平衡以及全球DNA羟基甲基化状态的酶的活性，可能是微生物信号的目标。
背景：国家推广委员会和技术委员会，FonCyT.
