E. coli NF73-1 Isolated From NASH Patients Aggravates NAFLD in Mice by Translocating Into the Liver and Stimulating M1 Polarization.
E. coli NF73-1 Isolated From NASH Patients Aggravates NAFLD in Mice by Translocating Into the Liver and Stimulating M1 Polarization.
复制标题
从 NASH 患者中分离出的大肠杆菌 NF73-1 通过易位至肝脏并刺激 M1 极化而加重小鼠 NAFLD
DOI：
10.3389/fcimb.2020.535940
复制
发表时间：
2020
影响因子：
5.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Zhang Y;Jiang W;Xu J;Wu N;Wang Y;Lin T;Liu Y;Liu Y
目的肠道菌群与非酒精性脂肪性肝病（NAFLD）的发生有关。我们从NASH患者的肠道中分离出大肠杆菌菌株NF 73 -1，然后研究其作用和潜在机制。方法采用16 S rRNA扩增子测序技术检测健康对照、NAFLD患者和NASH患者的细菌谱。高度富集E.从NASH患者中培养和分离大肠杆菌菌株。进行全基因组测序和比较基因组学以研究基因表达。根据饮食，将雄性C57 BL/6 J小鼠进一步分为正常饮食（ND）和高脂饮食（HFD）组。为了避免干扰细菌微生物群，将一些ND和HFD小鼠分组为“细菌耗尽”小鼠，并从第8周至第10周用广谱抗生素复合物（ABX）的鸡尾酒进行治疗。然后，对E. coli NF 73 -1经胃给药6周，以研究其在NAFLD发病过程中的作用和机制。结果非酒精性脂肪性肝病（NAFLD）患者肠粘膜中大肠埃希菌相对丰度明显增高，尤其是NASH患者。全基因组测序和比较基因组学研究结果表明，该基因在大肠杆菌中具有特异性表达谱。大肠杆菌NF 73 -1株，分离自NASH患者的肠粘膜。E. coli NF 73 -1对NAFLD的促进作用是独立的。仅HFD-NF 73 -1和HFD-ABX-NF 73 -1组有EGFP标记的E.大肠杆菌NF 73 -1在肝脏和肠道中检测到。随后，E. coli NF 73 -1经TLR 2/NLRP 3途径进入肝脏导致肝M1巨噬细胞增加。E. coli NF 73 -1激活mTOR-S6 K1-SREBP-1/PPAR-α信号通路，导致NAFLD小鼠甘油三酯从氧化代谢向合成代谢转变。结论E. coli NF 73 -1是NAFLD进展的关键触发因子。E. coli NF 73 -1可能是NAFLD患者的特异性菌株。
Objective The gut microbiota is associated with nonalcoholic fatty liver disease (NAFLD). We isolated the Escherichia coli strain NF73-1 from the intestines of a NASH patient and then investigated its effect and underlying mechanism. Methods 16S ribosomal RNA (16S rRNA) amplicon sequencing was used to detect bacterial profiles in healthy controls, NAFLD patients and NASH patients. Highly enriched E. coli strains were cultured and isolated from NASH patients. Whole-genome sequencing and comparative genomics were performed to investigate gene expression. Depending on the diet, male C57BL/6J mice were further grouped in normal diet (ND) and high-fat diet (HFD) groups. To avoid disturbing the bacterial microbiota, some of the ND and HFD mice were grouped as “bacteria-depleted” mice and treated with a cocktail of broad-spectrum antibiotic complex (ABX) from the 8th to 10th week. Then, E. coli NF73-1, the bacterial strain isolated from NASH patients, was administered transgastrically for 6 weeks to investigate its effect and mechanism in the pathogenic progression of NAFLD. Results The relative abundance of Escherichia increased significantly in the mucosa of NAFLD patients, especially NASH patients. The results from whole-genome sequencing and comparative genomics showed a specific gene expression profile in E. coli strain NF73-1, which was isolated from the intestinal mucosa of NASH patients. E. coli NF73-1 accelerates NAFLD independently. Only in the HFD-NF73-1 and HFD-ABX-NF73-1 groups were EGFP-labeled E. coli NF73-1 detected in the liver and intestine. Subsequently, translocation of E. coli NF73-1 into the liver led to an increase in hepatic M1 macrophages via the TLR2/NLRP3 pathway. Hepatic M1 macrophages induced by E. coli NF73-1 activated mTOR-S6K1-SREBP-1/PPAR-α signaling, causing a metabolic switch from triglyceride oxidation toward triglyceride synthesis in NAFLD mice. Conclusions E. coli NF73-1 is a critical trigger in the progression of NAFLD. E. coli NF73-1 might be a specific strain for NAFLD patients.
登录
查看更多内容
影响因子：
5.8
作者：
Gardner, Shea N.;Slezak, Tom;Hall, Barry G.
通讯作者：
Hall, Barry G.
影响因子：
25.7
作者：
Fouts, Derrick E.;Torralba, Manolito;Nelson, Karen E.;Brenner, David A.;Schnabl, Bernd
通讯作者：
Schnabl, Bernd
影响因子：
17.1
作者：
Balmer, Maria L.;Slack, Emma;Macpherson, Andrew J.
通讯作者：
Macpherson, Andrew J.
影响因子：
4.1
作者：
Kapil, Shweta;Duseja, Ajay;Chawla, Yogesh
通讯作者：
Chawla, Yogesh
DOI：
10.1152/ajpgi.00163.2009
发表时间：
2011-03-01
影响因子：
4.5
作者：
Csak, Timea;Velayudham, Arumugam;Szabo, Gyongyi
通讯作者：
Szabo, Gyongyi