The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review

Abstract

Parkinson’s disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome–gut–brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome–gut–brain axis might play in the underlying pathological mechanisms of Parkinson’s disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson’s disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome–gut–brain axis in the context of Parkinson’s disease.

Intestinal Barrier Dysfunction in the Absence of Systemic Inflammation Fails to Exacerbate Motor Dysfunction and Brain Pathology in a Mouse Model of Parkinson's Disease

“…There are numerous different pathways by which the gut could contribute to PD and in this study, we evaluated the contribution of intestinal hyperpermeability to the PD-like phenotype based on the following rationale: (1) data from our group has demonstrated intestinal hyperpermeability is observed in PD patients ( 8 , 76 , 77 ), (2) numerous conditions that may be risk factors for PD (e.g., diabetes, ulcerative colitis) are associated with intestinal hyperpermeability ( 78 , 79 ), and (3) intestinal hyperpermeability is associated with increased systemic inflammation which may drive neuroinflammation in PD ( 80 , 81 ). Thus, the rationale behind this study was to investigate if increased intestinal permeability could promote neuroinflammation and exacerbate the PD phenotype in ASO mice through a mechanism including intestinal and/or systemic inflammation.…”

Nutrition and Gut–Brain Pathways Impacting the Onset of Parkinson’s Disease

“…At the beginning of the 2000s, human postmortem studies led by Braak and colleagues suggested for the first time that such α-Syn pathology is not confined to the CNS and is also detectable in the ENS [56][57][58], which is a division of the peripheral nervous system that controls the gastrointestinal system [59]. The evidence of α-Syn pathology also in this system lent support to the theory that PD pathology could be initiated in the ENS [36] and that it could be spread from the gastrointestinal tract to the midbrain via the vagus nerve, resulting in the selective death of SNc dopamine neurons [57,60] (see Figure 1).…”

Immune Response Modifications in the Genetic Forms of Parkinson’s Disease: What Do We Know?

“…This pro-inflammatory status detected in DJ1 deficiency may also be mediated by gut microbiome dysregulation, thus altering the so-called gut–brain axis whose dysfunction is widely involved in the pathophysiology of PD [ 5 ]. Notably, DJ1 knock-out mice presented a significantly higher production of fecal calprotectin and monocyte chemotactic protein 1 (MCP-1), along with both serum and fecal higher levels of malonate [ 52 ], which can mediate the degeneration of dopaminergic neurons [ 53 ].…”

“…Notwithstanding, the connection between CNS and the periphery is also mediated by the strict connection between the gut and the brain, with the so-called gut–brain axis. Through this bidirectional pathway, toxins and cytokines produced by a dysregulated gut microbioma can reach the CNS either directly through the vagus nerve, or indirectly with the blood circulation where they are released as a consequence of microbial translocation due to augmented intestinal permeability [ 5 ].…”