Acute liver failure (ALF) patients are often accompanied by severe energy metabolism abnormalities and intestinal microecological imbalance. The intestinal mucosal barrier is severely damaged. Intestinal endotoxin can induce intestinal endotoxemia through the "Gut-Liver axis". More and more evidence shows that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are related to inflammatory bowel disease, but whether F. nucleatum is involved in the development of ALF and whether it affects the liver energy metabolism is unclear. This study first detected the abundance of F. nucleatum and its effect on ALF disease, and explored whether F. nucleatum aggravated liver inflammation in vitro and in vivo. Our data showed that liver tissues of ALF patients contained different abundances of F. nucleatum, which were related to the degree of liver inflammation. In addition, we found that F. nucleatum infection affected the energy metabolism of the liver during the development of ALF, inhibited the synthesis pathway of nicotinamide adenine dinucleotide (NAD+)'s salvage metabolism, and promoted inflammatory damage in the liver. In terms of mechanism, F. nucleatum inhibited NAD+ and the NAD+-dependent SIRT1/AMPK signaling pathway, and promoted liver damage of ALF. Fusobacterium nucleatum coordinates a molecular network including NAD+ and SIRT1 to control the progress of ALF. Detection and targeting of F. nucleatum and its related pathways may provide valuable insights for the treatment of ALF.

中文翻译：

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具核梭杆菌通过抑制 NAD+ 补救代谢途径促进急性肝功能衰竭的发展

急性肝功能衰竭（ALF）患者常伴有严重的能量代谢异常和肠道微生态失衡。肠黏膜屏障严重受损。肠道内毒素可通过“肠-肝轴”诱发肠道内毒素血症。越来越多的证据表明，肠道微生物群的成员，尤其是具核梭杆菌（F. nucleatum）与炎症性肠病有关，但具核梭杆菌是否参与了ALF的发生，是否影响肝脏能量代谢尚不清楚. 本研究首先检测了F. nucleatum 的丰度及其对ALF 疾病的影响，并探讨了F. nucleatum 在体外和体内是否会加重肝脏炎症。我们的数据显示，ALF 患者的肝组织中含有不同丰度的 F. nucleatum，与肝脏炎症程度有关。此外，我们发现F. nucleatum感染在ALF发展过程中影响了肝脏的能量代谢，抑制了烟酰胺腺嘌呤二核苷酸（NAD+）的补救代谢合成途径，促进了肝脏的炎症损伤。机制上，具核梭菌抑制NAD+和NAD+依赖的SIRT1/AMPK信号通路，促进ALF肝损伤。具核梭杆菌协调包括 NAD+ 和 SIRT1 的分子网络来控制 ALF 的进展。F. nucleatum 及其相关途径的检测和靶向可能为 ALF 的治疗提供有价值的见解。有核感染在ALF发展过程中影响肝脏的能量代谢，抑制烟酰胺腺嘌呤二核苷酸（NAD+）的补救代谢合成途径，促进肝脏炎症损伤。机制上，具核梭菌抑制NAD+和NAD+依赖的SIRT1/AMPK信号通路，促进ALF肝损伤。具核梭杆菌协调包括 NAD+ 和 SIRT1 的分子网络来控制 ALF 的进展。F. nucleatum 及其相关途径的检测和靶向可能为 ALF 的治疗提供有价值的见解。有核感染在ALF发展过程中影响肝脏的能量代谢，抑制烟酰胺腺嘌呤二核苷酸（NAD+）的补救代谢合成途径，促进肝脏炎症损伤。机制上，具核梭菌抑制NAD+和NAD+依赖的SIRT1/AMPK信号通路，促进ALF肝损伤。具核梭杆菌协调包括 NAD+ 和 SIRT1 的分子网络来控制 ALF 的进展。F. nucleatum 及其相关途径的检测和靶向可能为 ALF 的治疗提供有价值的见解。nucleatum抑制NAD+和NAD+依赖的SIRT1/AMPK信号通路，促进ALF肝损伤。具核梭杆菌协调包括 NAD+ 和 SIRT1 的分子网络来控制 ALF 的进展。F. nucleatum 及其相关途径的检测和靶向可能为 ALF 的治疗提供有价值的见解。nucleatum抑制NAD+和NAD+依赖的SIRT1/AMPK信号通路，促进ALF肝损伤。具核梭杆菌协调包括 NAD+ 和 SIRT1 的分子网络来控制 ALF 的进展。F. nucleatum 及其相关途径的检测和靶向可能为 ALF 的治疗提供有价值的见解。