Bacillus amyloliquefaciens SC06 alleviates obesity of ob/ob mice by improving intestinal microbiota and bile acid metabolism via the FXR signaling pathway

Dietary interventions with probiotics were widely reported to be effective to regulate obesity, and intestinal microbiota was considered as an important environmental factor. However, few reports focus on the microbiota-metabolites-phenotypic variables interactions in ob/ob mice, and have not been characterized in great details. In this study, we investigated the effects of Bacillus amyloliquefaciens SC06 on obesity, intestinal microbiota and bile acids metabolism of ob/ob mice by using biochemical testing, histochemical stain, high-throughput sequencing of 16S rRNA gene LC-MS/MS analysis and qRT-PCR. The results showed that SC06 ameliorated fat mass percentage, hepatic steatosis and liver lipid metabolism disorders and reshaped the gut microbiota and metabolites in male ob/ob mice, specifically deceasing in f_S24-7, p_TM7, s_Alistipes massiliensis, f_Rikenellaceae, f_Prevotellaceae, f_Lactobacillaceae, g_Alistipes, g_Flexispira, g_Lactobacillus, g_Odoribacter, g_AF12 and g_Prevotella and increasing in f_Bacteroidaceae, g_Bacteroides and f_Desulfovibrionaceae. Meanwhile, SC06 treatment groups had lower Ibuprofen and higher Glycodeoxycholic acid and 7-Dehydrocholesterol. Correlation analysis further clarify relationships between compositional changes in microbiota and alterations in the metabolites and phenotypes of ob/ob mice. Moreover, SC06 downregulated bile acid synthesis, export and re-absorption in liver, and increase ileum re-absorption into the blood in ob/ob mice, which may be mediated by FXR-SHP / FGF15 signaling pathway. These results suggested that Bacillus amyloliquefaciens could ameliorate obesity in male ob/ob mice by reshaping the intestinal microbial composition, changing metabolites and regulating bile acid metabolism via the FXR signaling pathway.

已有多项研究报道，益生菌膳食干预对肥胖具有调节作用，而肠道菌群被视作关键的环境调控因子。然而，目前鲜有研究关注ob/ob小鼠（ob/ob mice）体内的菌群-代谢物-表型变量互作关系，且相关机制尚未得到详尽阐释。本研究采用生化检测、组织化学染色、16S rRNA基因高通量测序、液相色谱-串联质谱（LC-MS/MS）分析以及实时定量聚合酶链式反应（qRT-PCR）等技术，探究了解淀粉芽孢杆菌（Bacillus amyloliquefaciens）SC06对ob/ob小鼠肥胖、肠道菌群及胆汁酸代谢的调控作用。研究结果显示，SC06可降低雄性ob/ob小鼠的体脂百分比，改善肝脂肪变性及肝脏脂质代谢紊乱，并重塑其肠道菌群与代谢物谱：具体表现为显著降低S24-7菌科（f_S24-7）、TM7菌门（p_TM7）、马赛阿里斯氏菌（s_Alistipes massiliensis）、理研菌科（f_Rikenellaceae）、普雷沃菌科（f_Prevotellaceae）、乳杆菌科（f_Lactobacillaceae）、阿里杆菌属（g_Alistipes）、屈曲螺菌属（g_Flexispira）、乳杆菌属（g_Lactobacillus）、气味杆菌属（g_Odoribacter）、AF12菌属以及普雷沃菌属（g_Prevotella）的相对丰度，同时提升拟杆菌科（f_Bacteroidaceae）、拟杆菌属（g_Bacteroides）以及脱硫弧菌科（f_Desulfovibrionaceae）的相对丰度。与此同时，经SC06干预的小鼠组中，布洛芬（Ibuprofen）含量显著降低，而甘氨酸脱氧胆酸（Glycodeoxycholic acid）与7-脱氢胆固醇（7-Dehydrocholesterol）的含量显著升高。相关性分析进一步阐明了ob/ob小鼠肠道菌群组成变化与代谢物及表型改变之间的关联。此外，SC06可下调ob/ob小鼠肝脏内的胆汁酸合成、转运与重吸收过程，并提升回肠对胆汁酸的血液重吸收能力，该调控作用可能通过法尼醇X受体（FXR）-小异二聚体伴侣（SHP）/成纤维细胞生长因子15（FGF15）信号通路介导。上述研究结果表明，解淀粉芽孢杆菌SC06可通过重塑雄性ob/ob小鼠的肠道菌群组成、调节代谢物谱以及经由FXR信号通路调控胆汁酸代谢，从而改善其肥胖症状。