The gut microbiota–oligodendrocyte axis: A promising pathway for modulating oligodendrocyte homeostasis and demyelination-associated disorders

Abstract

The bidirectional regulation between the gut microbiota and brain, known as gut–brain axis, has received significant attention. The myelin sheath, produced by oligodendrocytes or Schwann cells, is essential for efficient nervous signal transmission and the maintenance of brain function. Growing evidence shows that both oligodendrogenesis and myelination are modulated by gut microbiota and its metabolites, and when dysbiosis occurs, changes in the microbiota composition and/or associated metabolites may impact developmental myelination and the occurrence of neurodevelopmental disabilities. Although the link between the microbiota and demyelinating disease such as multiple sclerosis has been extensively studied, our knowledge about the role of the microbiota in other myelin-related disorders, such as neurodegenerative diseases, is limited. Mechanistically, the microbiota-oligodendrocyte axis is primarily mediated by factors such as inflammation, the vagus nerve, endocrine hormones, and microbiota metabolites as evidenced by metagenomics, metabolomics, vagotomy, and morphological and molecular approaches. Treatments targeting this axis include probiotics, prebiotics, microbial metabolites, herbal bioactive compounds, and specific dietary management. In addition to the commonly used approaches, viral vector-mediated tracing and gene manipulation, integrated multiomics and multicenter clinical trials will greatly promote the mechanistic and interventional studies and ultimately, the development of new preventive and therapeutic strategies against gut–oligodendrocyte axis-mediated brain impairments. Interestingly, recent findings showed that microbiota dysbiosis can be induced by hippocampal myelin damage and is reversible by myelin-targeted drugs, which provides new insights into understanding how hippocampus-based functional impairment (such as in neurodegenerative Alzheimer's disease) regulates the peripheral homeostasis of microbiota and associated systemic disorders.