The Role of the Gastrointestinal Microbiota in Parkinson's Disease

Abstract

Background/objectives: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons leading to debilitating motor and non-motor symptoms. Beyond its well-known neurological features, emerging evidence underscores the pivotal role of the gut-brain axis and gastrointestinal microbiota in PD pathogenesis. Dysbiosis has been strongly linked to PD and is associated with increased intestinal permeability, chronic inflammation, and the production of neurotoxic metabolites that may exacerbate neuronal damage.

Methods: This review delves into the complex interplay between PD and dysbiosis, shedding light on two peculiar subsets of dysbiosis, Helicobacter pylori infection and small-intestinal bacterial overgrowth. These conditions may not only contribute to PD progression but also influence therapeutic responses such as L-dopa efficacy.

Conclusions: The potential to modulate gut microbiota through probiotics, prebiotics, and synbiotics; fecal microbiota transplantation; and antibiotics represents a promising frontier for innovative PD treatments. Despite this potential, the current evidence is limited by small sample sizes and methodological variability across studies. Rigorous, large-scale, randomized placebo-controlled trials with standardized treatments in terms of composition, dosage, and duration are urgently needed to validate these findings and pave the way for microbiota-based therapeutic strategies in PD management.

Keywords: Helicobacter pylori; Parkinson’s disease; brain–gut axis; fecal microbiota transplantation; microbiota; prebiotics; probiotics; rifaximin; small-intestinal bacterial overgrowth; synbiotics.

Figure 1

Dysbiosis-induced damage to the GI tract triggers local inflammation and compromises the intestinal barrier, exposing the ENS to chronic inflammatory insults. This promotes α-synuclein misfolding, which propagates to the brain via the vagus nerve. Concurrently, chronic GI inflammation leads to the systemic release of inflammatory mediators (single-headed red arrow), weakening the blood–brain barrier. This allows the passage of proinflammatory cytokines, immune cells, antibodies, toxins, and antigens into the central nervous system (CNS), activating microglia and driving neuroinflammation. Microglial activation exacerbates neurodegeneration within the CNS. The double-headed yellow arrow represents the bidirectional communication pathway between the GI tract and the CNS, with the vagus nerve serving as the primary conduit. A self-perpetuating cycle ensues, wherein early alterations in GI motility (from the stomach to the colon), commonly observed in PD, exacerbate dysbiosis, further contributing, as mentioned, to PD pathogenesis.