Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China.
Front Cell Infect Microbiol. 2020 Dec 11;10:535940. doi: 10.3389/fcimb.2020.535940. eCollection 2020.
The gut microbiota is associated with nonalcoholic fatty liver disease (NAFLD). We isolated the strain NF73-1 from the intestines of a NASH patient and then investigated its effect and underlying mechanism.
16S ribosomal RNA (16S rRNA) amplicon sequencing was used to detect bacterial profiles in healthy controls, NAFLD patients and NASH patients. Highly enriched 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 8 to 10 week. Then, 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.
The relative abundance of 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 strain NF73-1, which was isolated from the intestinal mucosa of NASH patients. NF73-1 accelerates NAFLD independently. Only in the HFD-NF73-1 and HFD-ABX-NF73-1 groups were EGFP-labeled NF73-1 detected in the liver and intestine. Subsequently, translocation of NF73-1 into the liver led to an increase in hepatic M1 macrophages via the TLR2/NLRP3 pathway. Hepatic M1 macrophages induced by NF73-1 activated mTOR-S6K1-SREBP-1/PPAR-α signaling, causing a metabolic switch from triglyceride oxidation toward triglyceride synthesis in NAFLD mice.
NF73-1 is a critical trigger in the progression of NAFLD. NF73-1 might be a specific strain for NAFLD patients.
肠道微生物群与非酒精性脂肪性肝病（NAFLD）有关。我们从 NASH 患者的肠道中分离出 NF73-1 菌株，然后研究其作用及其潜在机制。
使用 16S 核糖体 RNA（16S rRNA）扩增子测序检测健康对照组、NAFLD 患者和 NASH 患者的细菌谱。从 NASH 患者中培养和分离高度富集的菌株。进行全基因组测序和比较基因组学研究以研究基因表达。根据饮食情况，雄性 C57BL/6J 小鼠进一步分为正常饮食（ND）和高脂肪饮食（HFD）组。为避免干扰细菌菌群，将一些 ND 和 HFD 小鼠分组为“细菌耗竭”小鼠，并从第 8 至 10 周开始用广谱抗生素复合物（ABX）鸡尾酒处理。然后，通过胃内给予从 NASH 患者肠道分离出的细菌菌株 NF73-1，研究其在 NAFLD 发病机制中的作用和机制。
在 NAFLD 患者，尤其是 NASH 患者的黏膜中， 的相对丰度显著增加。全基因组测序和比较基因组学的结果显示，从 NASH 患者肠道黏膜中分离出的 菌株 NF73-1 具有特定的基因表达谱。NF73-1 可独立加速 NAFLD。仅在 HFD-NF73-1 和 HFD-ABX-NF73-1 组中，肝脏和肠道中检测到 EGFP 标记的 NF73-1。随后，NF73-1 易位到肝脏中，通过 TLR2/NLRP3 途径导致肝 M1 巨噬细胞增加。NF73-1 诱导的肝 M1 巨噬细胞激活 mTOR-S6K1-SREBP-1/PPAR-α 信号通路，导致 NAFLD 小鼠的代谢从甘油三酯氧化向甘油三酯合成转变。
NF73-1 是 NAFLD 进展的关键触发因素。NF73-1 可能是 NAFLD 患者的特定菌株。
