A Narrative Review on the Role of Microbiota and Microglia in Premotor Symptoms of Parkinson's Disease.

With the advent of medical technology and the sustenance of a longer lifespan, an increase in the number of age-related neurodegenerative diseases, including Parkinson's disease (PD), is inevitable. Although current treatments for PD provide remarkable symptomatic relief for a few years, their side effects, combined with the progression in neurodegeneration, pose an urgent challenge for development of more effective treatments for this devastating disease. The challenge is further exacerbated by the unknown etiology in most PD cases. Nonetheless, progress in early identification of the premorbid/prodromal symptoms as well as understanding processes leading to their manifestation may help provide novel preventive and/or intervention strategies. The triad of the best-characterized and inter-related symptoms of prodromal PD include hyposmia (decrease sense of smell), constipation, and major depressive disorder (MDD). Recent revelations indicate a crucial role for the gut microbiota (GM) not only in maintaining the integrity of the gastrointestinal system but also that of the central nervous system via its bidirectional relationship with the brain, commonly referred to as the gut-brain-axis (GBA). Moreover, neuroinflammation, underscored by microglial activation, is believed to play a critical role in neurodegenerative as well as neuropsychiatric disorders including MDD. Here, we delve into the primary roles of GM/GBA and microglia, as well as their interactions, with the aim of providing novel diagnostic and/or treatments in PD. Regarding the treatments, we mention potential use of pre- post- or pro-biotics, and nicotinic or toll-like receptor modulators.