Background/aim

Alterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate gut microbiota composition and functionality in patients with morbid obesity with different degrees of MAFLD, as assessed by biopsy.

Subjects/methods

110 patients with morbid obesity were evaluated by biopsy obtained during bariatric surgery for MAFLD. Stool samples were collected prior to surgery for microbiota analysis.

Results

Gut microbiota from patients with steatosis and non-alcoholic steatohepatitis (NASH) were characterized by an enrichment in Enterobacteriaceae (an ethanol-producing bacteria), Acidaminococcus and Megasphaera and the depletion of Eggerthellaceae and Ruminococcaceae (SCFA-producing bacteria). MAFLD was also associated with enrichment of pathways related to proteinogenic amino acid degradation, succinate production, menaquinol-7 (K2-vitamin) biosynthesis, and saccharolytic and proteolytic fermentation. Basic histological hepatic alterations (steatosis, necroinflammatory activity, or fibrosis) were associated with specific changes in microbiota patterns. Overall, the core microbiome related to basic histological alterations in MAFLD showed an increase in Enterobacteriaceae and a decrease in Ruminococcaceae. Specifically, Escherichia coli was associated with steatosis and necroinflammatory activity, whilst Escherichia-shigella was associated with fibrosis and necroinflammatory activity.

Conclusions

We established a link between gut microbiota alterations and histological injury in liver diagnosis using biopsy. Harmful products such as ethanol or succinate may be involved in the pathogenesis and progression of MAFLD. Thus, these alterations in gut microbiota patterns and their possible metabolic pathways could add information to the classical predictors of MAFLD severity and suggest novel metabolic targets.

中文翻译：

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病态肥胖患者的非酒精性脂肪肝：肠道菌群轴作为潜在的病理生理学机制

背景/目标

肠道微生物群的改变与代谢疾病的发病机制有关，包括代谢相关脂肪肝病（MAFLD）。本研究的目的是通过活检评估患有不同程度 MAFLD 的病态肥胖患者的肠道微生物群组成和功能。

主题/方法

通过 MAFLD 减肥手术期间获得的活组织检查对 110 名病态肥胖患者进行了评估。在手术前收集粪便样本进行微生物群分析。

结果

脂肪变性和非酒精性脂肪性肝炎 (NASH) 患者肠道微生物群的特点是肠杆菌科（一种产乙醇细菌）、氨基酸球菌和巨球菌增多，而埃格氏菌科和瘤胃球菌科（产生 SCFA 的细菌）减少。MAFLD 还与蛋白质氨基酸降解、琥珀酸生产、menaquinol-7（K2-维生素）生物合成以及糖分解和蛋白水解发酵相关途径的富集相关。基本的肝脏组织学改变（脂肪变性、坏死性炎症活动或纤维化）与微生物群模式的特定变化相关。总体而言，与 MAFLD 基本组织学改变相关的核心微生物组显示肠杆菌科细菌增加，瘤胃球菌科细菌减少。具体而言，大肠杆菌与脂肪变性和坏死性炎症活动相关，而大肠杆菌-志贺氏菌与纤维化和坏死性炎症活动相关。

结论

我们利用活检在肝脏诊断中建立了肠道微生物群改变与组织学损伤之间的联系。乙醇或琥珀酸等有害产物可能参与MAFLD的发病机制和进展。因此，肠道微生物群模式及其可能的代谢途径的这些改变可以为 MAFLD 严重程度的经典预测因子添加信息，并提出新的代谢目标。