Zhang Zheng, Zhu Tian, Li Yang, Yu Bin, Tao Haiteng, Zhao Haibo, Cui Bo
Shandong Key Laboratory of Healthy Food Resources Exploration and Creation, School of Food Sciences and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
J Agric Food Chem. 2025 Apr 9;73(14):8277-8289. doi: 10.1021/acs.jafc.4c07966. Epub 2025 Apr 1.
As the adsorption receptor of bacteriophage tail protein, bacterial lipopolysaccharide (LPS) is a main culprit responsible for nonalcoholic fatty liver disease (NAFLD) caused by high-fat diets. However, few studies have focused on how the interaction between intestinal bacteriophages and bacterial LPS affects the development and progression of NAFLD. Herein, we determined that excessive fat intake significantly increases the levels of endogenous LPS, while the administration of beneficial metabolites of the intestinal microbiota (specifically butyrate) alleviated hepatic injury in rats. The beneficial mechanism of butyrate was attributed to the reprogramming of the structure of the intestinal DNA virome (primarily, phageome). Butyrate possesses the potential to augment bacteriophagic microbial diversity, thereby potentially facilitating interactions between intestinal bacteriophages and bacterial LPS (in the case of homologous phage), further improving mitochondrial dysfunction and reactive oxygen species production, which, in turn, lowered HepG2 cell damage. Likewise, fecal phage transplantation further confirmed that intestinal phages from rats that received butyrate could effectively interact with bacterial LPS to reduce liver damage in rats. Taken together, modifying the intestinal phageome is a promising treatment option for high-fat diet-related NAFLD.
作为噬菌体尾部蛋白的吸附受体，细菌脂多糖（LPS）是高脂饮食所致非酒精性脂肪性肝病（NAFLD）的主要元凶。然而，很少有研究关注肠道噬菌体与细菌LPS之间的相互作用如何影响NAFLD的发生发展。在此，我们确定过量脂肪摄入会显著增加内源性LPS水平，而给予肠道微生物群的有益代谢产物（特别是丁酸盐）可减轻大鼠肝脏损伤。丁酸盐的有益机制归因于肠道DNA病毒组（主要是噬菌体组）结构的重编程。丁酸盐具有增加噬菌体微生物多样性的潜力，从而可能促进肠道噬菌体与细菌LPS之间的相互作用（在同源噬菌体的情况下），进一步改善线粒体功能障碍和活性氧生成，进而降低HepG2细胞损伤。同样，粪便噬菌体移植进一步证实，来自接受丁酸盐的大鼠的肠道噬菌体可有效与细菌LPS相互作用，以减轻大鼠肝脏损伤。综上所述，改变肠道噬菌体组是高脂饮食相关NAFLD的一种有前景的治疗选择。
