Cebi Merve, Yilmaz Yusuf
Department of Medical Biology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Türkiye.
Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Türkiye.
Front Immunol. 2025 May 14;16:1575770. doi: 10.3389/fimmu.2025.1575770. eCollection 2025.
In recent years, the prevalence of chronic liver diseases, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), has increased significantly. This upward trend is largely associated with lifestyle-related factors such as unhealthy dietary habits, physical inactivity, and various environmental influences. Among the key elements contributing to the pathogenesis of MASLD, the integrity of the intestinal epithelial barrier emerges as a critical determinant, given its central role in maintaining immune homeostasis along the gut-liver axis. Disruption of this barrier, often driven by excessive consumption of saturated fats and refined carbohydrates in combination with low dietary fiber intake, can lead to microbial dysbiosis. This imbalance in the gut microbiota triggers immune dysregulation and promotes systemic inflammation, thereby exacerbating hepatic injury. This review discusses the contribution of epithelial barrier dysfunction to the development and progression of MASLD, with a particular focus on how increased intestinal permeability may initiate and sustain chronic liver inflammation. Additionally, the influence of dietary and environmental factors on epithelial integrity, immune responses, and the inflammatory cascade is addressed. A better understanding of the complex interplay between gut barrier impairment, immune modulation, and liver pathology may offer valuable insights into MASLD pathophysiology and contribute to the development of more targeted therapeutic strategies.
近年来,慢性肝病,尤其是代谢功能障碍相关脂肪性肝病(MASLD)的患病率显著上升。这种上升趋势在很大程度上与不健康的饮食习惯、缺乏体育活动以及各种环境影响等生活方式相关因素有关。在导致MASLD发病机制的关键因素中,肠道上皮屏障的完整性成为一个关键决定因素,因为它在维持肠道-肝脏轴的免疫稳态中起着核心作用。这种屏障的破坏通常是由饱和脂肪和精制碳水化合物的过量摄入以及膳食纤维摄入量低共同驱动的,会导致微生物群落失调。肠道微生物群的这种失衡会引发免疫失调并促进全身炎症,从而加剧肝损伤。本综述讨论了上皮屏障功能障碍对MASLD发生和发展的作用,特别关注肠道通透性增加如何引发和维持慢性肝脏炎症。此外,还探讨了饮食和环境因素对上皮完整性、免疫反应和炎症级联反应的影响。更好地理解肠道屏障损伤、免疫调节和肝脏病理之间的复杂相互作用,可能为MASLD的病理生理学提供有价值的见解,并有助于制定更有针对性的治疗策略。