Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH).
Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH).
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DOI：
10.1016/j.jpge.2016.01.004
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发表时间：
2016-05
影响因子：
0.9
通讯作者：
Guerreiro AS
中科院分区：
文献类型：
--
作者：
Cortez-Pinto H;Borralho P;Machado J;Lopes MT;Gato IV;Santos AM;Guerreiro AS
肠道微生物群可能在非酒精性脂肪性肝炎（NASH）中发挥作用。先前的研究表明，益生元和益生菌可能会阻止脂肪性肝炎的进展。旨在阐明 Synbiotic 2000®Forte (Synb) 在预防或改善饮食诱发的脂肪性肝炎方面的潜在作用，特别是在纤维化进展方面，以及这种干预措施与肠道微生物群组成和内毒素血症之间的关系。将 27 只 C57BL/6 小鼠分为三组：食物饮食（CD，n = 7）；高脂胆碱缺乏饮食（HFCD，n = 10）和补充有 Synbiotic 2000®Forte（四种益生菌菌株和四种益生元混合物）的 HFCD 饮食（HFCD + Synb，n = 10）。在第 6 周和第 18 周时，收集血液样本（脂多糖测定 - LPS）、盲肠粪便（肠道微生物群）和肝组织（组织学）进行分析。两只 HCFD 饮食小鼠均在第 6 周和第 18 周时出现脂肪性肝炎并伴有气球样膨胀，这与 CD 小鼠相反。 6 周和 18 周时 HFCD 和 HFCD + Synb 的组织学评分的比较显示，在脂肪变性、炎症或气球样变方面没有显着差异。用天狼星红评估纤维化和平滑肌细胞活化程度，HFCD 小鼠的纤维化程度明显更高；添加 Synb 可显着减少第 6 周和第 18 周时的纤维化。第 6 周时，HFCD 和 HFCD + Synb 的血清内毒素水平同样增加；然而，在第 18 周，HFCD + Synb 的内毒素水平显着低于 HFCD。 HFCD 与 CD 的肠道微生物群在厚壁菌门和拟杆菌门方面没有显示出显着差异，无论是在 6 周还是 18 周时；变形菌在第 6 周 (3.3) 和第 18 周 (7.5) 增加，而添加 Synb 导致第 18 周减少 (-3.90)。梭杆菌在第 18 周显着增加 (10.0)，但添加 Synb 后则减少 (5.2)。 Synbiotic 2000®Forte 能够调节小鼠肠道微生物群，减少纤维化程度，同时减少内毒素血症。
Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis. To clarify the potential effect of Synbiotic 2000®Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia. Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000®Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay – LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis. Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla Firmicutes and Bacteroidetes, either at 6 or 18 weeks; Proteobacteria increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (−3.90). Fusobacteria markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2). Synbiotic 2000®Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.