Potential Role of Probiotics and Fecal Microbiota Transplantation in the Treatment of Parkinson's Disease

Introduction

Parkinson’s disease (PD) is a debilitating neurodegenerative disease characterized by both motor and non-motor features (Dutta et al., 2019). Indeed, PD a multisystem disorder with motor symptoms (tremors, rigidity, akinesia/bradykinesia, and postural abnormalities) and non-motor symptoms (NMS) including neuropsychiatric symptoms, cognitive impairment and other symptoms of the gastrointestinal (GI) tract including constipation, urinary incontinence, bloating and anosmia are also observed (Draoui et al., 2020 ; Jankovic, 2008 ; Kalia & Lang, 2015 ; Pfeiffer, 2016). Current line treatments of PD including surgical interventions and pharmacological therapies are mostly symptomatic and do not provide neuroprotection in addition to their adverse effects (i.e., dyskinesia), and limitations.

PD characterized histopathologically by the degeneration of dopaminergic neurons of the substanitia nigra (SN) of the midbrain and the pathological aggregation of alpha-synuclein (α-syn) protein forming Lewy Bodies and Lewy Neurites (Klann et al., 2022). Despite the fact that the exact cause of PD is still unknown, recent advances have revealed that there may be multifaceted interactions between genetic predispositions and exposure to environmental factors such as infectious agents and toxins (Tan et al., 2021).

Despite the substantial progress in the study of PD, the exact mechanisms and pathways responsible for its onset and progression remain elusive. Compelling evidence suggests that gut microbiota dysbiosis may play a significant role in the pathogenesis of PD. The hypothesis of a “gut-brain axis,” a bidirectional communication link between the central and enteric nervous system (ENS) and the gastrointestinal (GI) system, has been supported by the discovery of α-syn aggregates in peripheral regions, such as the ENS even though they most frequently found in the brain (Chao et al., 2020; Klann et al., 2022). Indeed, a recent study using a mouse model of which pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer revealed that pathogenic α-syn may be transmitted to the brain along the vagus nerve (S. Kim et al., 2019). This could disrupt the function of the peripheral and ENS and subsequently the central nervous system (CNS) (Klann et al., 2022). Additionally, the GI system represents an area of vulnerability for pathogen entrance, which has been theorized as highly involved in the pathogenesis of PD (Breen et al., 2019; Klingelhoefer & Reichmann, 2015b). Indeed, a number of preclinical and clinical investigations have shown that PD is associated with altered gut bacteria, disturbed intestinal permeability, and intestinal inflammation (Tan et al., 2021). Moreover, a mounting evidence points to a possible role for the gut microbiome-brain axis in the underlying pathological mechanisms of PD including the onset of NMS, such as gastrointestinal manifestations which frequently appear before the onset of motor symptoms characteristic of the disease and its related diagnosis (Klann et al., 2022). In this context, it has recently been shown that microbial-targeted interventions, such as probiotics and fecal microbiota transplantation (FMT) are believed to have a beneficial role in alleviating PD symptoms and providing neuroprotection. This chapter briefly reviews current knowledge on altered gut microbiota in PD, followed by the importance of its targeted interventions, with a particular focus on the use of probiotics and FMT in PD.