The microbiome-gut-brain axis in Parkinson disease - from basic research to the clinic

The prominence of gastrointestinal dysfunction among the non-motor features of Parkinson disease (PD) indicates a close bidirectional link between the brain and the gut. This Review discusses the proposed roles of gut-related factors in PD development, progression and treatment responses, and as therapeutic targets. Evidence for a close bidirectional link between the brain and the gut has led to a paradigm shift in neurology, especially in the case of Parkinson disease (PD), in which gastrointestinal dysfunction is a prominent feature. Over the past decade, numerous high-quality preclinical and clinical publications have shed light on the highly complex relationship between the gut and the brain in PD, providing potential for the development of new biomarkers and therapeutics. With the advent of high-throughput sequencing, the role of the gut microbiome has been specifically highlighted. Here, we provide a critical review of the literature on the microbiome-gut-brain axis in PD and present perspectives that will be useful for clinical practice. We begin with an overview of the gut-brain axis in PD, including the potential roles and interrelationships of the vagus nerve, alpha-synuclein in the enteric nervous system, altered intestinal permeability and inflammation, and gut microbes and their metabolic activities. The sections that follow synthesize the proposed roles of gut-related factors in the development and progression of, in responses to PD treatment, and as therapeutic targets. Finally, we summarize current knowledge gaps and challenges and delineate future directions for the field.

Automated summary

The close bidirectional link between the brain and the gut in Parkinson disease has led to a paradigm shift in neurology. Gut-related factors play significant roles in the development, progression, and treatment responses of Parkinson disease, and could potentially be targeted for therapeutics. The gut microbiome, in particular, has been highlighted as an important factor. Future directions for the field include further understanding of the gut-brain axis and addressing current knowledge gaps and challenges.