Background and aims Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship between specific strains and NAFLD has not been fully elucidated. We aimed to investigate whether Akkermansia muciniphila and Bifidobacterium bifidum could prevent NAFLD, the effects of their action alone or in combination, possible mechanisms, and modulation of the gut microbiota. Methods Mice were fed with high-fat diets (HFD) for 20 weeks, in which experimental groups were pretreated with quadruple antibiotics and then given the corresponding bacterial solution or PBS. The expression of the glycolipid metabolism indicators, liver, and intestinal farnesol X receptors (FXR), and intestinal mucosal tight junction proteins were detected. We also analyzed the alterations of inflammatory and immune status and the gut microbiota of mice. Results Both strains were able to attenuate mass gain (p<0.001), insulin resistance (p<0.001), and liver lipid deposition (p<0.001). They also reduced the levels of the pro-inflammatory factors (p<0.05) and the proportion of Th17 (p<0.001), while elevating the proportion of Treg (p<0.01). Both strains activated hepatic FXR while suppressing intestinal FXR (p<0.05), and elevating tight junction protein expression (p<0.05). We also perceived changes in the gut microbiota and found both strains were able to synergize beneficial microbiota to function. Conclusions Administration of A. muciniphila or B. bifidum alone or in combination was protective against HFD-induced NAFLD formation and could be used as alternative treatment strategy for NAFLD after further exploration.

中文翻译：

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Akkermansia muciniphila 和双歧杆菌通过调节 FXR 表达和肠道微生物群预防 NAFLD。

背景与目的非酒精性脂肪性肝病（NAFLD）与肠道菌群密切相关，已成为全球最常见的慢性肝病，但特定菌株与NAFLD之间的关系尚未完全阐明。我们的目的是研究粘蛋白阿克曼氏菌和两歧双歧杆菌是否可以预防 NAFLD、它们单独或联合作用的效果、可能的机制以及肠道微生物群的调节。方法 小鼠高脂饮食（HFD）喂养20周，实验组给予四联抗生素预处理，然后给予相应菌液或PBS。检测糖脂代谢指标、肝、肠法尼醇X受体（FXR）、肠粘膜紧密连接蛋白的表达量。我们还分析了小鼠炎症和免疫状态以及肠道微生物群的变化。结果 两种菌株均能够减弱质量增加 (p<0.001)、胰岛素抵抗 (p<0.001) 和肝脏脂质沉积 (p<0.001)。他们还降低了促炎因子的水平（p<0.05）和 Th17 的比例（p<0.001），同时提高了 Treg 的比例（p<0.01）。两种菌株均激活肝脏 FXR，同时抑制肠道 FXR (p<0.05)，并提高紧密连接蛋白表达 (p<0.05)。我们还观察到肠道微生物群的变化，发现两种菌株都能够协同有益微生物群发挥作用。结论 施用 A. muciniphila 或 B.