Pellegrini Carolina, Fornai Matteo, D'Antongiovanni Vanessa, Antonioli Luca, Bernardini Nunzia, Derkinderen Pascal
Unit of Histology and Medical Embryology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Lancet Gastroenterol Hepatol. 2023 Jan;8(1):66-80. doi: 10.1016/S2468-1253(22)00241-2. Epub 2022 Nov 2.
The intestinal barrier, which primarily consists of a mucus layer, an epithelial barrier, and a gut vascular barrier, has a crucial role in health and disease by facilitating nutrient absorption and preventing the entry of pathogens. The intestinal barrier is in close contact with gut microbiota on its luminal side and with enteric neurons and glial cells on its tissue side. Mounting evidence now suggests that the intestinal barrier is compromised not only in digestive disorders, but also in disorders of the central nervous system (CNS), such as Parkinson's disease, autism spectrum disorder, depression, multiple sclerosis, and Alzheimer's disease. After providing an overview of the structure and functions of the intestinal barrier, we review existing preclinical and clinical studies supporting the notion that intestinal barrier dysfunction is present in neurological, neurodevelopmental, and psychiatric disorders. On the basis of this evidence, we discuss the mechanisms that possibly link gut barrier dysfunction and CNS disorders and the potential impact that evaluating enteric barriers in brain disorders could have on clinical practice, in terms of novel diagnostic and therapeutic strategies, in the near future.
肠道屏障主要由黏液层、上皮屏障和肠道血管屏障组成，通过促进营养物质吸收和防止病原体进入，在健康和疾病中发挥关键作用。肠道屏障在其管腔侧与肠道微生物群密切接触，在其组织侧与肠神经元和神经胶质细胞密切接触。现在越来越多的证据表明，肠道屏障不仅在消化系统疾病中受损，在中枢神经系统（CNS）疾病中也会受损，如帕金森病、自闭症谱系障碍、抑郁症、多发性硬化症和阿尔茨海默病。在概述肠道屏障的结构和功能后，我们回顾了现有的临床前和临床研究，这些研究支持了肠道屏障功能障碍存在于神经、神经发育和精神疾病中的观点。基于这些证据，我们讨论了可能将肠道屏障功能障碍与中枢神经系统疾病联系起来的机制，以及在不久的将来，评估肠道屏障在脑部疾病中的作用可能对临床实践产生的潜在影响，包括新的诊断和治疗策略。
