The Gut and Parkinson's Disease—A Bidirectional Pathway

Abstract

Humans evolved a symbiotic relationship with their gut microbiome, a complex microbial community composed of bacteria, archaea, protists, and viruses, including bacteriophages. The enteric nervous system (ENS) is a gateway for the bidirectional communication between the brain and the gut, mostly through the vagus nerve (VN). Environmental exposure plays a pivotal role in both the composition and functionality of the gut microbiome and may contribute to susceptibility to neurodegenerative disorders, such as Parkinson's disease (PD). The neuropathological hallmark of PD is the widespread appearance of alpha-synuclein aggregates in both the central and peripheral nervous systems, including the ENS. Many studies suggest that gut toxins can induce the formation of α-syn aggregates in the ENS, which may then be transmitted in a prion-like manner to the CNS through the VN. PD is strongly associated with aging and its negative effects on homeostatic mechanisms protecting from inflammation, oxidative stress, and protein malfunction. In this mini-review, we revisit some landmark discoveries in the field of Parkinson's research and focus on the gut-brain axis. In the process, we highlight evidence showing gut-associated dysbiosis and related microbial-derived components as important players and risk factors for PD. Therefore, the gut microbiome emerges as a potential target for protective measures aiming to prevent PD onset.

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

“…Lewy bodies are present not only in the central nervous system (CNS) but also in the enteric nervous system (ENS) of the intestine, so it is not only the brain but also the gut that is involved in PD pathogenesis 10,11 . In 2002, Del Tredici et al postulated that neurotoxic α-synucleins may originate in the gut and migrate to the brain via the vagal nerve, the gutbrain-axis, causing neuronal cell death and inflammation in the substantia nigra 12,13,14,15,16 . This theory was recently supported by studies in rat models 17,18,19 , which confirmed that α-synuclein transport can be purged by vagal nerve resection 20 .…”

Long-Term Neurological Threats of COVID-19: A Call to Update the Thinking About the Outcomes of the Coronavirus Pandemic

“…Parkinson's disease (PD) is a common neurodegenerative disorder associated with the progressive loss of dopaminergic neurons located in the midbrain nucleus substantia nigra pars compacta (SNpc) due to the accumulation of αsynuclein (α-syn) aggregates. The Braak hypothesis (9) for the etiology of sporadic Parkinson's disease (PD) proposes that a neurotropic virus invading neural tissue through the nasal cavity and the gastrointestinal tract causes α-syn to turn into a promiscuous binder and be transmitted, prion-like, to key areas such as the SNpc (15). Interestingly, the prodromal or preclinical phase of PD is also characterized by olfactory and gastrointestinal symptoms (17).…”

DJ-1 (Park7) affects the gut microbiome, metabolites and development of Innate Lymphoid cells (ILCs)

“…Recent discoveries in the field of the gut microbiome and their role in the neurodegeneration in patients and animal models highlights an important link among each other (67). As most of the common neurodegenerative diseases such as Alzheimer's disease and PD occurs late in the life (40,68) biomarkers allowing early diagnosis would be invaluable.…”

“…Immune cells are capable of engaging in direct communication with enteric neurons (18,20). The extent of the functional impact of neuro-immune synapses is not clear yet however published studies advocated that activated immune cells can temper neuronal activity via the release of neurotransmitters, metabolites and cytokines (19,39,40). Based on the common occurrence of GIT symptoms in PD, dysbiosis among PD patients, and evidence that the microbiota impacts CNS function, we hypothesized that DJ-1 protein could also be involved in the regulation of the gut microbiome and inflammation.…”