Microbiome, Parkinson’s Disease and Molecular Mimicry

Abstract

Parkinson’s Disease (PD) is typically classified as a neurodegenerative disease affecting the motor system. Recent evidence, however, has uncovered the presence of Lewy bodies in locations outside the CNS, in direct contact with the external environment, including the olfactory bulbs and the enteric nervous system. This, combined with the ability of alpha-synuclein (αS) to propagate in a prion-like manner, has supported the hypothesis that the resident microbial community, commonly referred to as microbiota, might play a causative role in the development of PD. In this article, we will be reviewing current knowledge on the importance of the microbiota in PD pathology, concentrating our investigation on mechanisms of microbiota-host interactions that might become harmful and favor the onset of PD. Such processes, which include the secretion of bacterial amyloid proteins or other metabolites, may influence the aggregation propensity of αS directly or indirectly, for example by favoring a pro-inflammatory environment in the gut. Thus, while the development of PD has not yet being associated with a unique microbial species, more data will be necessary to examine potential harmful interactions between the microbiota and the host, and to understand their relevance in PD pathogenesis.

Microbiota-Gut-Brain Signaling: A Minireview

“…Butyrate, on the other hand, is generated by bacteria of the phylum Firmicutes (83). Data is accumulating to demonstrate that the gut microbiota influences the perception of pain (84); that it can influence the pathogenesis of Alzheimer's disease (85)(86)(87), Parkinson's disease (88), and some psychiatric disorders (89), such as attention deficit hyperactivity disorder (90) and autism spectrum disorder (91); and that it can be associated with problems of cognitive impairment (92). The relationship between various health problems and activation of the microbiota-gut-brain axis is schematically presented in Fig.…”

Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms

“…Mounting evidence suggest that the intestinal microbiota may be the triggering factor of PD pathology. Specifically, the gut microbiota encoded proteins and their metabolites can initiate accumulation of misfolding of α-Syn in the enteric nervous system through molecular mimicry and intestinal mucosal immunoinflammatory mechanisms, which thereafter could act in a prion-like fashion and spread along the gut-brain axis via vagus nerve, eventually leading to the development of PD pathology (Friedland, 2015;Klingelhoefer and Reichmann, 2015;Pellegrini et al, 2018;Ho et al, 2019;Miraglia and Colla, 2019;Cirstea et al, 2020;Zheng et al, 2020). Multiple lines of preclinical and clinical evidences support the role of gut microbiota dysfunction in various aspects of PD pathogenesis: (i) according to the widely accepted Braak Staging hypothesis about the pathogenesis of PD, α-Syn pathology may begin in the intestine and spread to the brain through the vagus nerve.…”

The Gut and Parkinson's Disease—A Bidirectional Pathway

“…The microbiota of PD patients exhibits a pro-inflammatory profile (128, 129) due to increased intestinal permeability to endotoxins (lipopolysaccharide) (130). Bacterial amyloids may also favor a pro-inflammatory environment in the gut (131). A common bacterial component, the Curli fimbriae, share structural and biophysical properties with amyloids and are produced by E. coli through coordinated biosynthetic processes (132).…”