Sadegh Hamidreza, Choi Jaesung P
Centre for Inflammation, Faculty of Science, School of Life Sciences, Centenary Institute and University of Technology Sydney, Sydney, NSW 2007, Australia.
School of Biomedical Sciences, UNSW Sydney, Kensington, NSW 2052, Australia.
Int J Mol Sci. 2025 Sep 4;26(17):8622. doi: 10.3390/ijms26178622.
Cerebral cavernous malformation (CCM) is a cluster of abnormal blood vessels in the brain that leads to severe neurological deficits, seizures, and fatal hemorrhagic stroke. Currently, there is no available drug treatment for CCM. Most CCMs are conservatively managed by observing change in appearance (MRI), recent hemorrhage, or any clinical symptoms. Neurosurgery is the only current treatment option, but it is only effective in a few cases. Since most CCM lesions are surgically inaccessible, when left untreated they lead to severe neurological deficits, seizures, and fatal hemorrhagic stroke. Hence, new non-invasive, safe, and effective treatment strategies are urgently needed. Recent research has identified gut microbiome dysbiosis and its innate immune response as the critical stimulus in experimental CCM pathogenesis, demonstrating the importance of the gut-brain axis in CCM. Importantly, CCM patients also manifest gut microbiome dysbiosis and gut barrier health can impact CCM disease course. This review highlights the emerging involvement of the gut microbiome in CCM pathogenesis and its potential as a therapeutic target. While preclinical data suggest mechanistic links, the lack of clinical intervention studies limits current applicability and underscores the need for translational research.
脑海绵状血管畸形（CCM）是大脑中一组异常血管，可导致严重的神经功能缺损、癫痫发作和致命性出血性中风。目前，尚无针对CCM的药物治疗方法。大多数CCM通过观察外观变化（磁共振成像）、近期出血情况或任何临床症状进行保守治疗。神经外科手术是目前唯一的治疗选择，但仅在少数情况下有效。由于大多数CCM病变无法通过手术切除，若不进行治疗，会导致严重的神经功能缺损、癫痫发作和致命性出血性中风。因此，迫切需要新的非侵入性、安全且有效的治疗策略。最近的研究已确定肠道微生物群失调及其先天免疫反应是实验性CCM发病机制中的关键刺激因素，这表明了肠-脑轴在CCM中的重要性。重要的是，CCM患者也表现出肠道微生物群失调，且肠道屏障健康会影响CCM的病程。本综述强调了肠道微生物群在CCM发病机制中的新作用及其作为治疗靶点的潜力。虽然临床前数据表明存在机制联系，但缺乏临床干预研究限制了当前的适用性，并突出了转化研究的必要性。
