肠道屏障功能障碍在非酒精性脂肪肝病中的早期诊断标志物探索
Exploration of Early Diagnostic Biomarkers for Intestinal Barrier Dysfunction in Non-Alcoholic Fatty Liver Disease
摘要: 本文主要探讨了肠道屏障功能障碍在非酒精性脂肪肝病中作为早期诊断标志物的潜力。本文探讨了肠道屏障功能障碍在NAFLD发病机制中的关键作用。包括肠道屏障发生障碍后肠道细菌产物的易位、肠道微生物群的失衡在NAFLD中的作用。肠道通透性标志物、代谢组学、肠道微生物菌群可以作为非酒精性脂肪肝病早期诊断策略。这些策略的结合有望在未来为NAFLD的早期诊断和治疗提供更为全面和有效的解决方案。
Abstract: This article primarily explores the potential of intestinal barrier dysfunction as an early diagnostic biomarker in non-alcoholic fatty liver disease (NAFLD). It investigates the critical role of intestinal barrier dysfunction in the pathogenesis of NAFLD, including the translocation of gut bacterial products following barrier disruption and the impact of gut microbiota imbalance in NAFLD. Markers of intestinal permeability, metabolomics, and gut microbiota can serve as early diagnostic strategies for non-alcoholic fatty liver disease. The combination of these strategies is expected to provide more comprehensive and effective solutions for the early diagnosis and treatment of NAFLD in the future.
文章引用：李庄巍. 肠道屏障功能障碍在非酒精性脂肪肝病中的早期诊断标志物探索[J]. 临床医学进展, 2025, 15(2): 315-321. https://doi.org/10.12677/acm.2025.152349

参考文献

[1] Albillos, A., de Gottardi, A. and Rescigno, M. (2020) The Gut-Liver Axis in Liver Disease: Pathophysiological Basis for Therapy. Journal of Hepatology, 72, 558-577. [Google Scholar] [CrossRef] [PubMed]
[2] Chopyk, D.M. and Grakoui, A. (2020) Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders. Gastroenterology, 159, 849-863. [Google Scholar] [CrossRef] [PubMed]
[3] 周子含. 基于多组学技术研究非酒精性脂肪肝小鼠盲肠菌群与代谢物的变化[D]: [硕士学位论文]. 雅安: 四川农业大学, 2020.
[4] Ferro, D., Baratta, F., Pastori, D., Cocomello, N., Colantoni, A., Angelico, F., et al. (2020) New Insights into the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Gut-Derived Lipopolysaccharides and Oxidative Stress. Nutrients, 12, Article 2762. [Google Scholar] [CrossRef] [PubMed]
[5] 丛硕. 凯里酸汤对非酒精性脂肪性肝病的影响及机制研究[D]: [博士学位论文]. 贵阳: 贵州医科大学, 2021.
[6] Kessoku, T., Kobayashi, T., Tanaka, K., Yamamoto, A., Takahashi, K., Iwaki, M., et al. (2021) The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target. International Journal of Molecular Sciences, 22, Article 8161. [Google Scholar] [CrossRef] [PubMed]
[7] Kobayashi, T., Iwaki, M., Nakajima, A., Nogami, A. and Yoneda, M. (2022). Current Research on the Pathogenesis of NAFLD/NASH and the Gut-Liver Axis: Gut Microbiota, Dysbiosis, and Leaky-Gut Syndrome. International Journal of Molecular Sciences, 23, Article 11689.[CrossRef] [PubMed]
[8] 郑瑞鹏. 基于微生物组学的慢性肝病临床特点及粪菌移植延缓肝硬化大鼠疾病进程的机制研究[D]: [博士学位论文]. 长春: 吉林大学, 2020.
[9] 冯璟. 原发性肝癌患者肠道及血液微生物的群落特征及应用初探[D]: [博士学位论文]. 太原: 山西大学, 2020.
[10] 刘颖初. 基于miR-34a调控SIRT1/PPARα探讨调肝祛脂方改善非酒精性脂肪肝的作用机制[D]: [硕士学位论文]. 北京: 北京中医药大学, 2022.
[11] 许趁意. 基于助脾散精理论的“胆汁酸-FXR-肠道激素”轴调控T2DM血糖稳态的作用机制研究[D]: [博士学位论文]. 成都: 成都中医药大学, 2022.
[12] An, L., Wirth, U., Koch, D., Schirren, M., Drefs, M., Koliogiannis, D., et al. (2022) The Role of Gut-Derived Lipopolysaccharides and the Intestinal Barrier in Fatty Liver Diseases. Journal of Gastrointestinal Surgery, 26, 671-683. [Google Scholar] [CrossRef] [PubMed]
[13] 周晴中. 益生菌[M]. 北京: 北京大学出版社: 2020.
[14] Schirone, L., Overi, D., Carpino, G., Carnevale, R., De Falco, E., Nocella, C., et al. (2024) Oleuropein, a Component of Extra Virgin Olive Oil, Improves Liver Steatosis and Lobular Inflammation by Lipopolysaccharides-TLR4 Axis Downregulation. International Journal of Molecular Sciences, 25, Article 5580. [Google Scholar] [CrossRef] [PubMed]
[15] 李恩有. 呼出气代谢组学与疾病的诊断[M]. 北京: 人民卫生出版社: 2022.
[16] 费欢欢. 男性脂肪性肝病患者肠道机械屏障功能变化的研究[D]: [硕士学位论文]. 合肥: 安徽医科大学, 2020.
[17] Johansson, M.E.V., Phillipson, M., Petersson, J., Velcich, A., Holm, L. and Hansson, G.C. (2008) The Inner of the Two Muc2 Mucin-Dependent Mucus Layers in Colon Is Devoid of Bacteria. Proceedings of the National Academy of Sciences of the United States of America, 105, 15064-15069. [Google Scholar] [CrossRef] [PubMed]
[18] Bergheim, I., Weber, S., Vos, M., Krämer, S., Volynets, V., Kaserouni, S., et al. (2008) Antibiotics Protect against Fructose-Induced Hepatic Lipid Accumulation in Mice: Role of Endotoxin. Journal of Hepatology, 48, 983-992. [Google Scholar] [CrossRef] [PubMed]
[19] Keita, Å.V. and Söderholm, J.D. (2010) The Intestinal Barrier and Its Regulation by Neuroimmune Factors. Neurogastroenterology & Motility, 22, 718-733. [Google Scholar] [CrossRef] [PubMed]
[20] Dlugosz, A., Nowak, P., D’Amato, M., Mohammadian Kermani, G., Nyström, J., Abdurahman, S., et al. (2015) Increased Serum Levels of Lipopolysaccharide and Antiflagellin Antibodies in Patients with Diarrhea‐predominant Irritable Bowel Syndrome. Neurogastroenterology & Motility, 27, 1747-1754. [Google Scholar] [CrossRef] [PubMed]
[21] Kirpich, I.A., Marsano, L.S. and McClain, C.J. (2015) Gut-Liver Axis, Nutrition, and Non-Alcoholic Fatty Liver Disease. Clinical Biochemistry, 48, 923-930. [Google Scholar] [CrossRef] [PubMed]
[22] Cani, P.D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A.M., Delzenne, N.M., et al. (2008) Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice. Diabetes, 57, 1470-1481. [Google Scholar] [CrossRef] [PubMed]
[23] Taguchi, D., Shirakami, Y., Sakai, H., Maeda, T., Miwa, T., Kubota, M., et al. (2024) High-Fat Diet Delays Liver Fibrosis Recovery and Promotes Hepatocarcinogenesis in Rat Liver Cirrhosis Model. Nutrients, 16, Article 2506. [Google Scholar] [CrossRef] [PubMed]
[24] Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W.Z., Strowig, T., et al. (2012) Inflammasome-Mediated Dysbiosis Regulates Progression of NAFLD and Obesity. Nature, 482, 179-185. [Google Scholar] [CrossRef] [PubMed]
[25] Zhao, Z., Wang, Z., Zhou, D., Han, Y., Ma, F., Hu, Z., et al. (2021) Sodium Butyrate Supplementation Inhibits Hepatic Steatosis by Stimulating Liver Kinase B1 and Insulin-Induced Gene. Cellular and Molecular Gastroenterology and Hepatology, 12, 857-871. [Google Scholar] [CrossRef] [PubMed]
[26] 刘莹莹. 基于肠道菌群的化滞柔肝颗粒治疗非酒精性脂肪肝作用机制研究[D]: [硕士学位论文]. 北京: 北京中医药大学, 2022.
[27] Nier, A., Engstler, A.J., Maier, I.B. and Bergheim, I. (2017) Markers of Intestinal Permeability Are Already Altered in Early Stages of Non-Alcoholic Fatty Liver Disease: Studies in Children. PLOS ONE, 12, e0183282. [Google Scholar] [CrossRef] [PubMed]
[28] De Munck, T.J.I., Xu, P., Verwijs, H.J.A., Masclee, A.A.M., Jonkers, D., Verbeek, J., et al. (2020) Intestinal Permeability in Human Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta‐Analysis. Liver International, 40, 2906-2916. [Google Scholar] [CrossRef] [PubMed]
[29] 张晓芬. 基于广泛靶向代谢组学的胆管癌和非酒精性脂肪性肝炎代谢特征研究[D]: [博士学位论文]. 郑州: 郑州大学, 2021.
[30] Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P.K., Cazanave, S., et al. (2017) The Presence and Severity of Nonalcoholic Steatohepatitis Is Associated with Specific Changes in Circulating Bile Acids. Hepatology, 67, 534-548. [Google Scholar] [CrossRef] [PubMed]
[31] Lake, A.D., Novak, P., Shipkova, P., Aranibar, N., Robertson, D.G., Reily, M.D., Lehman-McKeeman, L.D., Vaillan-court, R.R. and Cherrington, N.J. (2015) Branched Chain Amino Acid Metabolism Profiles in Progressive Human Nonalcoholic Fatty Liver Disease. Amino Acids, 47, 603-615.
[32] Sinha, R., Lockman, K.A., Homer, N., Bower, E., Brinkman, P., Knobel, H., et al. (2018) A Study of Breath Metabolome in Non-Alcoholic Fatty Liver Disease. Journal of Hepatology, 68, S557-S558. [Google Scholar] [CrossRef] 
[33] Lee, K.S., Cho, Y., Kim, H., Hwang, H., Cho, J.W., Lee, Y., et al. (2022) Association of Metabolomic Change and Treatment Response in Patients with Non-Alcoholic Fatty Liver Disease. Biomedicines, 10, Article 1216. [Google Scholar] [CrossRef] [PubMed]
[34] Jennison, E. and Byrne, C.D. (2021) The Role of the Gut Microbiome and Diet in the Pathogenesis of Non-Alcoholic Fatty Liver Disease. Clinical and Molecular Hepatology, 27, 22-43. [Google Scholar] [CrossRef] [PubMed]
[35] Lee, G., You, H.J., Bajaj, J.S., Joo, S.K., Yu, J., Park, S., et al. (2020) Distinct Signatures of Gut Microbiome and Metabolites Associated with Significant Fibrosis in Non-Obese NAFLD. Nature Communications, 11, Article No. 4982. [Google Scholar] [CrossRef] [PubMed]
[36] Hoyles, L., Fernández-Real, J., Federici, M., Serino, M., Abbott, J., Charpentier, J., et al. (2018) Publisher Correction: Molecular Phenomics and Metagenomics of Hepatic Steatosis in Non-Diabetic Obese Women. Nature Medicine, 24, 1628-1628. [Google Scholar] [CrossRef] [PubMed]
[37] 樊晓明, 俞富军. 肝纤维化研究前沿[M]. 上海: 复旦大学出版社: 2015.
[38] Poretsky, R., Rodriguez-R, L.M., Luo, C., Tsementzi, D. and Konstantinidis, K.T. (2014) Strengths and Limitations of 16S Rrna Gene Amplicon Sequencing in Revealing Temporal Microbial Community Dynamics. PLOS ONE, 9, e93827. [Google Scholar] [CrossRef] [PubMed]
[39] 张玉琴. 帕金森病与非酒精性脂肪性肝病的关系及相关机制研究[D]: [博士学位论文]. 杭州: 浙江大学, 2021.
[40] Koutoukidis, D.A., Yen, S., Gomez Castro, P., Misheva, M., Jebb, S.A., Aveyard, P., et al. (2024) Changes in Intestinal Permeability and Gut Microbiota Following Diet-Induced Weight Loss in Patients with Metabolic Dysfunction-Associated Steatohepatitis and Liver Fibrosis. Gut Microbes, 16, Article ID: 2392864. [Google Scholar] [CrossRef] [PubMed]
[41] Stevens, B.R., Goel, R., Seungbum, K., Richards, E.M., Holbert, R.C., Pepine, C.J., et al. (2017) Increased Human Intestinal Barrier Permeability Plasma Biomarkers Zonulin and FABP2 Correlated with Plasma LPS and Altered Gut Microbiome in Anxiety or Depression. Gut, 67, 1555-1557. [Google Scholar] [CrossRef] [PubMed]
[42] 李玉林. 分子病理学[M]. 北京: 人民卫生出版社: 2022.
[43] 高金龙. 基于代谢组学研究n-3多不饱和脂肪酸对妊娠期糖尿病母鼠的子代成年后的影响及机制[D]: [博士学位论文]. 杭州: 浙江大学, 2020.
[44] 郭希菊, 姜鹤, 何峰峰, 陈光远, 欧阳威, 吴安山, 李林, 范俊, 谷雨, 田广兰, 郝金小, 邓兰兰, 伍桂枝, 冯存河, 杨红霞. 现代内科学[M]. 北京: 世界图书出版公司, 2020.
[45] Yi, S., Cong, Q., Zhu, Y. and Xu, Q. (2023) Mechanisms of Action of Mesenchymal Stem Cells in Metabolic-Associated Fatty Liver Disease. Stem Cells International, 2023, Article ID: 3919002. [Google Scholar] [CrossRef] [PubMed]

为你推荐