The Role of Gut Microbiome Dysbiosis in Alpha-Synuclein Aggregation and Parkinson’s Disease Progression: Can Microbial Markers Predict Clinical Outcomes?

Abstract

Background: Growing research indicates that an imbalanced gut microbiome may interfere with gut-brain axis, potentially worsening alpha-synuclein (α-syn) buildup in early Parkinson’s disease (PD). This review aims to provide an overview and critically discuss the current knowledge about gut bacteria influencing α-syn pathology and assesses if specific microbial patterns can forecast disease progression, a possible method of diagnosis before traditional PD symptoms, and maybe as a treatment option to abate PD progression. Summary: Gut microbiome imbalances may speed up α-syn-related damage in early PD through immune, neural, metabolic, inflammatory pathways. The confirmed involvement of the GI tract could serve as progression markers, opening doors for potential alternative diagnosis. Consequently, therapeutic strategies that target the gut microbiome, such as dietary interventions, probiotics, and FMT are being explored as potential ways to mitigate disease progression. Methodology: We reviewed various studies, literature reviews, original papers, published on Pubmed between 2015–2022 to investigate relationships between PD and microbiota-gut-brain axis disruptions, α-syn spread in PD. Key evidence came from Histopathology, Immunocytochemistry, Neuroimaging (fMRI) of PD patients, investigations of bacteria metabolites, antibiotic-induced microbiota depletion, and probiotic/prebiotic interventions. Results: GI symptoms, such as constipation, IBD, etc often precede motor symptoms, which indicates early involvement of the gut-brain axis. The data we referenced indicates that gut microbiota alterations play a significant role in PD development. For example, lower levels of Prevotella and higher levels of Enterobacteriaceae have been linked to PD symptoms. Some microbes like Lactobacillus, Bifidobacterium, and Akkermansia are found in higher amounts in PD patients compared to anti-inflammatory bacteria in healthy control groups.Furthermore, Dysbiosis leads to increased intestinal permeability and systemic inflammation, potentially triggering α-syn aggregation in the ENS. Studies have shown that fecal microbiota transplants from PD patients to mice exacerbate motor symptoms, highlighting a causal link. Key Messages: Gut microbiome imbalances may speed up α-syn-related damage in early PD through immune, neural, metabolic, inflammatory pathways. The confirmed involvement of the GI tract could serve as progression markers, opening doors for potential alternative diagnosis. Consequently, therapeutic strategies that target the gut microbiome, such as dietary interventions, probiotics, and FMT are being explored as potential ways to mitigate disease progression.