Ju Tianjuan, Zhang Yaoyuan, Liu Lipeng, Zhao Xitong, Li Xinwei, Liu Changfeng, Sun Shukai, Wu Li-An
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Neural Regen Res. 2025 Apr 29. doi: 10.4103/NRR.NRR-D-24-01419.
Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis, which refers to the crosstalk between the gut and the central nervous system. More importantly, mitochondria have been considered prominent mediators of the interplay between the gut microbiota and the brain. Intestinal microbes may modulate mitochondrial function in the central nervous system to affect the progression of neurodegenerative diseases. Mitochondria are essential for meeting the host's substantial neuronal metabolic demands, maintaining excitability, and facilitating synaptic transmission. Dysfunctional mitochondria are considered critical hallmarks of various neurodegenerative diseases. Therefore, this review provides novel insights into the intricate roles of gut microbiota-mitochondrial crosstalk in the underlying mechanisms during the progression of neurodegeneration, as well as the existing potential therapeutic strategies for neurodegenerative disorders. These suggest intestinal microbiota-mitochondrial interaction play a crucial role in the occurrence and development of neurodegenerative diseases, and targeting this interaction may be a promising therapeutic approach to neurodegenerative diseases. However, this review found that there was relatively little research on the effect of this crosstalk on other neurodegenerative diseases, such as Huntington's disease and Multiple sclerosis, and the potential therapeutic strategies were translated into clinical trials, which face many challenges in developing personalized treatment plans based on the unique gut microbiota of different individuals.
新出现的证据表明，肠道微生物群通过肠-脑轴与多种神经退行性疾病的病理表现密切相关，肠-脑轴指的是肠道与中枢神经系统之间的相互作用。更重要的是，线粒体被认为是肠道微生物群与大脑之间相互作用的重要介质。肠道微生物可能调节中枢神经系统中的线粒体功能，以影响神经退行性疾病的进展。线粒体对于满足宿主大量的神经元代谢需求、维持兴奋性以及促进突触传递至关重要。功能失调的线粒体被认为是各种神经退行性疾病的关键标志。因此，本综述为肠道微生物群-线粒体相互作用在神经退行性变进展过程中的潜在机制以及神经退行性疾病现有的潜在治疗策略提供了新的见解。这些表明肠道微生物群-线粒体相互作用在神经退行性疾病的发生和发展中起关键作用，针对这种相互作用可能是治疗神经退行性疾病的一种有前景的方法。然而，本综述发现，关于这种相互作用对其他神经退行性疾病（如亨廷顿舞蹈症和多发性硬化症）的影响以及潜在治疗策略转化为临床试验的研究相对较少，在基于不同个体独特的肠道微生物群制定个性化治疗方案方面面临许多挑战。
