Luo Xi, Wang Kai, Jiang Changtao
Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Cell Host Microbe. 2025 Jun 11;33(6):836-853. doi: 10.1016/j.chom.2025.04.020. Epub 2025 May 26.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide. The liver communicates with the intestine, in large part through the gut microbiota. Microbial enzymes are key mediators that affect the progression of MASLD and the more severe metabolic dysfunction-associated steatohepatitis (MASH). These enzymes contribute to the metabolism or biosynthesis of steroids, fatty acids, amino acids, ethanol, choline, and intestinal hormones that contribute to disease progression. Additionally, dysbiosis and functional alterations in the microbiota compromise the intestinal barrier, increasing its permeability to bacterial metabolites and liver exposure to microbial-associated molecular patterns (MAMPs), thereby exacerbating liver inflammation and fibrosis. Furthermore, functional alterations in the gut microbiota can modulate intestinal signaling pathways through metabolites or gut hormones, subsequently affecting hepatic metabolism. A deeper understanding of the roles of the gut microbiota and microbial enzymes in MASH will facilitate the development of personalized treatments targeting specific gut microbes or functional enzymes.
代谢功能障碍相关脂肪性肝病（MASLD）是全球最普遍的肝脏疾病。肝脏与肠道之间存在广泛的交流，其中大部分是通过肠道微生物群进行的。微生物酶是影响MASLD进展以及更严重的代谢功能障碍相关脂肪性肝炎（MASH）的关键介质。这些酶参与类固醇、脂肪酸、氨基酸、乙醇、胆碱和肠道激素的代谢或生物合成，从而促进疾病进展。此外，微生物群的失调和功能改变会损害肠道屏障，增加其对细菌代谢产物的通透性以及肝脏对微生物相关分子模式（MAMPs）的暴露，从而加剧肝脏炎症和纤维化。此外，肠道微生物群的功能改变可通过代谢产物或肠道激素调节肠道信号通路，进而影响肝脏代谢。深入了解肠道微生物群和微生物酶在MASH中的作用将有助于开发针对特定肠道微生物或功能酶的个性化治疗方法。
