Dumitru Andrei, Tocia Cristina, Bădescu Alina-Cristina, Trandafir Anamaria, Alexandrescu Luana, Popescu Razvan, Dumitru Eugen, Chisoi Anca, Manea Mihaela, Matei Elena, Cozaru Georgeta Camelia, Rugină Sorin
"Sf. Apostol Andrei" Clinical Emergency County Hospital, Constanta, Romania.
Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania.
Medicine (Baltimore). 2025 May 23;104(21):e42476. doi: 10.1097/MD.0000000000042476.
Recent research highlights a potential link between metabolic dysfunction-associated steatotic liver disease (MASLD) and intestinal barrier dysfunction. Increased intestinal permeability (IP) may facilitate the translocation of bacteria, endotoxins (e.g., lipopolysaccharides [LPS]), and pathogen-associated molecular patterns into the portal venous system, fostering a pro-inflammatory environment and contributing to liver inflammation. This study aimed to identify correlations between intestinal barrier biomarkers (occludin, LPS, and intestinal-type fatty-acid-binding proteins [I-FABP]) and MASLD. A single-center prospective cross-sectional study was conducted, including 72 MASLD patients and 68 healthy controls. Fibroscan-controlled attenuation parameter (CAP) was performed in all subjects. Blood samples were analyzed for biochemical parameters, and serum levels of occludin, LPS, and I-FABP were measured using the ELISA method with the Human occludin, LPS, and I-FABP ELISA Kit test systems (FineTest, Wuhan, China). LPS and I-FABP levels were significantly higher in MASLD patients compared to controls, with the highest LPS levels observed in the diabetic MASLD subgroup. Occludin levels showed no statistically significant differences between groups. All 3 biomarkers were positively correlated with BMI, with the highest levels in obese subjects. LPS was positively correlated with CRP levels. Using Fibroscan-CAP, we found a positive correlation between LPS and both liver stiffness and CAP score, as well as between I-FABP and liver stiffness. MASLD patients exhibit increased IP, with enterocyte injury present irrespective of diabetes status, though more pronounced in diabetic MASLD. Occludin does not appear to be a reliable biomarker for evaluating intestinal barrier function in MASLD. Obesity is linked to elevated biomarkers, suggesting an association between increased IP and obesity. I-FABP and LPS may serve as noninvasive biomarkers for assessing hepatic fibrosis and steatosis in MASLD patients. Notably, LPS, given its correlation with elevated CRP levels, could be utilized as a marker of disease progression and severity.
近期研究突显了代谢功能障碍相关脂肪性肝病（MASLD）与肠道屏障功能障碍之间的潜在联系。肠道通透性增加（IP）可能会促进细菌、内毒素（如脂多糖 [LPS]）以及病原体相关分子模式向门静脉系统的移位，从而营造促炎环境并导致肝脏炎症。本研究旨在确定肠道屏障生物标志物（闭合蛋白、LPS和肠型脂肪酸结合蛋白 [I-FABP]）与MASLD之间的相关性。开展了一项单中心前瞻性横断面研究，纳入72例MASLD患者和68名健康对照者。对所有受试者进行了Fibroscan控制衰减参数（CAP）检测。分析血样的生化参数，并使用人闭合蛋白、LPS和I-FABP ELISA试剂盒检测系统（武汉菲恩生物）通过ELISA法测定血清中闭合蛋白、LPS和I-FABP的水平。与对照组相比，MASLD患者的LPS和I-FABP水平显著更高，在糖尿病性MASLD亚组中观察到最高的LPS水平。各组间闭合蛋白水平无统计学显著差异。所有这3种生物标志物均与体重指数呈正相关，在肥胖受试者中水平最高。LPS与C反应蛋白（CRP）水平呈正相关。使用Fibroscan-CAP，我们发现LPS与肝脏硬度和CAP评分之间、I-FABP与肝脏硬度之间均呈正相关。MASLD患者表现出IP增加，无论糖尿病状态如何均存在肠上皮细胞损伤，不过在糖尿病性MASLD中更为明显。闭合蛋白似乎不是评估MASLD肠道屏障功能的可靠生物标志物。肥胖与生物标志物升高有关，提示IP增加与肥胖之间存在关联。I-FABP和LPS可用作评估MASLD患者肝纤维化和脂肪变性的非侵入性生物标志物。值得注意的是，鉴于LPS与升高的CRP水平相关，它可用作疾病进展和严重程度的标志物。
