Abstract: 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

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, gut microbiota, gut?brain axis, microbiota?mitochondria crosstalk, neurodegenerative diseases, neuroinflammation, Parkinson’s disease, probiotic, short chain fatty acid