Therapies for Parkinson’s disease and the gut microbiome: evidence for bidirectional connection

Abstract

The gut brain axis (GBA), a bidirectional communication pathway has often been linked to health and disease, and gut microbiota (GM), a key component of this pathway shown to be altered in Parkinson’s disease (PD), are suggested to contribute to the pathogenesis of PD. There are few studies that report the impact of oral medication therapy on GM, however, there are even fewer studies that discuss the impact of other treatments such as device assisted therapies (DAT) including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel infusion (LCIG) and photobiomodulation (PBM) and how these might impact GM. Here, we review the literature and summarize findings of the potential contributions of GM to the heterogenous clinical response to pharmaceutical therapies among individuals with PD. We also discuss the potential interactions between the GM and DATs such as DBS and LCIG and present evidence for alterations in GM in response to DATs. Given the complexity and highly individual nature of the GM of patients with PD and the potential influence that other external factors such as diet, lifestyle, medications, stage of the disease and other comorbidities, further investigations into the response of GM to therapies are worthy of future study in prospective, controlled trials as well as medication naïve individuals. Such detailed studies will help us further comprehend the relationship between GM in PD patients, and will help investigate the potential of targeting GM associated changes as a treatment avenue for PD.

Neuromodulation and the Gut–Brain Axis: Therapeutic Mechanisms and Implications for Gastrointestinal and Neurological Disorders

“…Notably, the microbiota’s reaction to DAT exposure varies depending on how long it continues. Although the exact causes of these alterations are not entirely known, they may be brought on by changing physiological responses and reciprocal interactions between gut microbiota and DATs [ 101 ].…”

Neuromodulation and the Gut-Brain Axis: Therapeutic Mechanisms and Implications for Gastrointestinal and Neurological Disorders

“…Notably, the microbiota's reaction to DAT exposure varies depending on how long it continues. Although the exact causes of these alterations are not entirely known, they may be brought on by changing physiological responses and reciprocal interactions between gut microbiota and DATs [82].…”

The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson’s Disease Animal Models—A Systematic Review

“…The observation that Lewy bodies first appear in the gut and that gastrointestinal symptoms precede motor symptoms has led to the hypothesis that PD may originate in the gut as a multisystemic pathology [11]. This could be explained through the gut-brain axis, a bidirectional communication system between the brain and the gut involving microbiota, and its relationship with immune, endocrine, metabolic, and neural pathways [12]. α-Syn has been shown to accumulate bidirectionally along this axis in the brain and the enteric nervous system (ENS) [13].…”

“…Braak's hypothesis proposes a dual hit model of sporadic body-first PD wherein a pathogen triggers the gastrointestinal tract (GIT) and olfactory nerve, allowing for subsequent retrograde α-syn transmission via the vagus and olfactory bulb to the SNpc [14,15]. Indeed, in prodromal PD, increased intestinal permeability or 'leaky gut' consequent to mucous injury and dysbiosis contributes to local and systemic inflammation, gut α-syn aggregation, blood-brain barrier (BBB) permeabilization, and microglial activation [12,[14][15][16]. Microbiota involvement seems to be mediated by the CD4+ T cell response, which leads to local IFN-γ, IL-17, TNF, and IL-5 secretion [15].…”