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UBC Theses and Dissertations

Microbiome-gut-brain axis and dietary interventions in Parkinson’s disease Keymanesh, Shayan


Parkinson’s disease (PD) is a complex neurodegenerative disorder with a multifaceted etiology involving the nervous, gastrointestinal, and immune systems. Although motor dysfunctions are the most notable clinical feature of PD, the disease is also associated with various non-motor symptoms, many of which occur before the onset of motor signs. Prodromal gastrointestinal symptoms, alterations in the gut microbiome, and trans-vagal propagation of α-synuclein aggregates from the gut to the brainstem suggest a possible intestinal origin for PD. Another pathophysiological feature of PD is the inefficient utilization of glucose by neuronal cells, which leads to bioenergetic deficits in the brain. Current PD therapies only provide symptomatic relief without addressing the underlying causes. Therefore, dietary interventions have emerged as a promising therapeutic approach that can target multiple disease mechanisms. For example, the Mediterranean diet (MeDi) and the ketogenic diet (KD) have shown promise in alleviating gastrointestinal and bioenergetic deficits in PD, respectively, while providing symptomatic relief. The KD provides an alternative source of energy to the brain, while the MeDi replenishes the population of short-chain fatty acid (SCFA)-producing bacteria. However, classical KDs may unfavorably alter the gut microbiome and decrease SCFA levels. Therefore, combining the principles of the MeDi and KD may allow us to harness the potential benefits of both dietary interventions while maintaining gut health. This thesis will analyze the literature on PD pathophysiology, particularly with respect to the microbiome-gut-brain axis, as well as the biological mechanisms of dietary interventions to propose a mechanistic framework for the application of Mediterranean-ketogenic diets in PD. Additionally, to investigate the safety and feasibility of Mediterranean-ketogenic diets (MeDi-KD) and MeDi diets supplemented with medium-chain triglycerides (MeDi-MCT) in PD patients, an open-label, randomized, cross-over clinical trial was designed, the protocol for which will also be presented.

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