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

Oct 31, 2025Neurotoxicity research

How Gut Bacteria and Brain Immune Cells May Relate to Early Movement Symptoms in Parkinson’s Disease

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Abstract

The triad of prodromal symptoms for Parkinson's disease includes hyposmia, constipation, and major depressive disorder.

Age-related neurodegenerative diseases, such as Parkinson's disease, are expected to rise due to longer life spans.
Current Parkinson's treatments offer temporary relief but are limited by side effects and disease progression.
Understanding early symptoms and their underlying processes could lead to new prevention and intervention strategies.
The gut microbiota is significantly involved in both gastrointestinal and central nervous system health through its connection to the brain.
Neuroinflammation and microglial activation are linked to both neurodegenerative and neuropsychiatric disorders, including major depressive disorder.
Potential treatments discussed include pre- and probiotics, as well as modulators of nicotinic and toll-like receptors.

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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.

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

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