Exosome-mediated gut–brain axis signaling in neurodegenerative diseases: Mechanisms, experimental evidence, and therapeutic perspectives—A narrative review

Abstract

The stomach and the brain are connected by a sophisticated two-way communication mechanism called the gut–brain axis. Extracellular vesicles, particularly exosomes, that move bioactive substances between the stomach and the brain, such as proteins, lipids, metabolites, and microRNAs, may improve the gut–brain axis. In the past years, the role of exosome-mediated communication has been recognized as significant in relation to the etiology, continued progression, and potential treatment of neurodegenerative disorders. The authors of this review article present a summary of the current understanding of the relationship of gut microbiome, exosome biogenesis, and the pathophysiological development of neurodegenerative diseases. Evidence from laboratory studies, animal studies, and newly emerging human studies suggests that microbiome-based metabolites and inflammatory mediators may modulate how exosomes are produced, what they carry, and how they interact with the blood–brain barrier. These exosomal signals may impact neuroinflammation, neuronal signaling, and the spread of pathological proteins of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In addition, they examine some possible ways to target the gut–brain axis from a therapeutic perspective, including manipulating the gut microbiome, providing probiotics and/or prebiotics, performing fecal microbiota transplantation, and/or using engineered extracellular vesicles as vehicles for drug delivery. The authors also outline some of the methodological differences that make it difficult to assess the effects of exosomes.