Data_Sheet_2_Hepatoprotection of Probiotics Against Non-Alcoholic Fatty Liver Disease in vivo: A Systematic Review.docx

Probiotic supplements have been increasingly reported for their usefulness in delaying the development and progression of non-alcoholic fatty liver disease (NAFLD). Literature on the impact of probiotics on NAFLD covered various aspects of the disease. This study was undertaken to systematically review in vivo findings on hepatoprotection of probiotics against NAFLD. The literature search was performed through Cochrane, PubMed/MEDLINE, Embase, and Web of Science databases. Interventions of known probiotics in NAFLD-induced animal model with at least one measurable NAFLD-related parameter were included. The data were extracted by all authors independently. Quality assessment was conducted using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE's) Risk of Bias (RoB) tool. P-values of measures were compared inter- and intra-study for each parameter. Forty-four probiotic-based studies of NAFLD-induced rodents were shortlisted. The majority of the studies were presented with low/unclear risk of bias. Probiotics improved the histopathology of NAFLD rodents (primary outcome). Most of the probiotic-supplemented NAFLD rodents were presented with mixed effects on serum liver enzymes but with improved hepatic and serum lipid profiles (including increased serum high-density lipoprotein cholesterol). The findings were generally accompanied by downregulation of hepatic lipogenic, oxidative, and inflammatory signallings. Probiotics were found to modulate gut microbiota composition and its products, and intestinal permeability. Probiotics also resulted in better glycaemic control and reduced liver weight. Altogether, the present qualitative appraisals strongly implied the hepatoprotective potential of probiotics against NAFLD in vivo.

越来越多的研究报道显示，益生菌补充剂可有效延缓非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）的发生与进展。现有探讨益生菌对非酒精性脂肪性肝病影响的文献，覆盖了该疾病的多个研究维度。本研究旨在系统综述益生菌对抗非酒精性脂肪性肝病的体内保肝作用相关研究结果。本研究通过Cochrane、PubMed/MEDLINE、Embase及Web of Science数据库开展文献检索。纳入标准为：研究需在非酒精性脂肪性肝病诱导的动物模型中应用已明确的益生菌干预措施，且至少包含一项可量化的非酒精性脂肪性肝病相关检测指标。所有作者均独立完成数据提取流程。研究质量评估采用实验动物系统评价中心（Systematic Review Center for Laboratory Animal Experimentation, SYRCLE）偏倚风险（Risk of Bias, RoB）工具进行。针对各项检测参数，分别比较研究内与研究间的对应P值。最终共筛选出44项基于益生菌的非酒精性脂肪性肝病诱导啮齿类动物模型研究。绝大多数研究的偏倚风险等级为低或不确定。益生菌可改善非酒精性脂肪性肝病啮齿类模型的组织病理学表现（主要结局指标）。多数经益生菌补充的非酒精性脂肪性肝病啮齿类模型，其血清肝酶指标呈现混合效应，但肝脏与血清脂质谱得到显著改善，包括血清高密度脂蛋白胆固醇水平升高。上述研究结果通常伴随肝脏内脂肪生成、氧化应激及炎症信号通路的下调表达。研究发现，益生菌可调节肠道菌群组成及其代谢产物，并改善肠道通透性。此外，益生菌可改善血糖控制效果，并降低肝脏重量。综合来看，本次定性评价有力证实了益生菌在体内对抗非酒精性脂肪性肝病的保肝潜力。