Exploring the Connection Between the Gut Microbiome and Parkinson’s Disease Symptom Progression and Pathology: Implications for Supplementary Treatment Options

Abstract

The contribution of the microbiota to induce gastrointestinal inflammation is hypothesized to be a key component of alpha-synuclein (aSyn) aggregation within the gastrointestinal (GI) tract in the pathological progression of Parkinson’s disease (PD). The function of the GI tract is governed by a system of neurons that form part of the enteric nervous system (ENS). The ENS hosts 100–500 million nerve cells within two thin layers lining the GI tract. The gut-brain axis (GBA) is the major communication pathway between the ENS and the central nervous system. It has become increasingly clear that the microbiota in the gut are key regulators of GBA function and help to maintain homeostasis in the immune and endocrine systems. The GBA may act as a possible etiological launching pad for the pathogenesis of age-related neurodegenerative diseases, such as PD, because of an imbalance in the gut microbiota. PD is a multi-faceted illness with multiple biological, immunological, and environmental factors contributing to its pathological progression. Interestingly, individuals with PD have an altered gut microbiota compared to healthy individuals. However, there is a lack of literature describing the relationship between microbiota composition in the gut and symptom progression in PD patients. This review article examines how the pathology and symptomology of PD may originate from dysregulated signaling in the ENS. We then discuss by targeting the imbalance within the gut microbiota such as prebiotics and probiotics, some of the prodromal symptoms might be alleviated, possibly curtailing the pathological spread of aSyn and ensuing debilitating motor symptoms.

The Bifunctional Dimer Caffeine-Indan Attenuates α-Synuclein Misfolding, Neurodegeneration and Behavioural Deficits After Chronic Stimulation of Adenosine A1 Receptors

“…These metabolic stability studies indicated that similar metabolites were observed in mouse, rat and human microsomes, suggesting that mice and rats are appropriate models for future animal studies of 18 F-C8-6-I. Emerging evidence supports the key role of the gut-brain connection in the pathogenesis of PD [65][66][67]. Our pharmacokinetics studies demonstrated a relatively high level of intestinal localization of 18 F-C8-6-I dimer probes which further suggests the potential applicability of our probe in gut-brain studies.…”

Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis

“…The accumulation of SOD1 G93A in the spinal cord and neurons serves as a molecular marker of the progression of ALS in SOD1 G93A mice, beginning at 2 months of age; the aggregation of human SOD1 G93A protein is observed in the white and gray matter of the lumbar spine, accompanied by increased levels of glial fibrillary acidic protein (GFAP) and neuromuscular symptoms such as decreased muscle strength, which are indicative of neuromuscular degeneration. Additionally, disruption of GFAP in the ENS suggests that the gut microbiota affects gut neuromuscular structure as well as function, and that imbalance in the gut microbiota may act as a potential trigger for degenerative diseases ( 81 ). Further research is needed to fully understand this relationship.…”