The dichotomous role of the gut microbiome in exacerbating and ameliorating neurodegenerative disorders

ABSTRACT

Introduction

Age related neurodegenerative disorders affect millions of people around the world. The role of the gut microbiome (GM) in neurodegenerative disorders has been elucidated over the past few years. Dysbiosis of the gut microbiome ultimately results in neurodegeneration. However, the gut microbiome can be modulated to promote neuro-resilience.

Areas covered

This review is focused on demonstrating the role of the gut microbiome in host physiology in Parkinson’s disease (PD) and other neurodegenerative disorders. We will discuss how the microbiome will impact neurodegeneration in PD, Alzheimer’s Disease (AD), Multiple sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and finally discuss how the gut microbiome can be influenced through diet and lifestyle.

Expert opinion

Currently, much of the focus has been to study the mechanisms by which the microbiome induces neuroinflammation and neurodegeneration in PD, AD, MS, ALS. In particular, the role of certain dietary flavonoids in regulation of gut microbiome to promote neuro-resilience. Polyphenol prebiotics delivered in combination with probiotics (synbiotics) present an exciting new avenue to harness the microbiome to attenuate immune inflammatory responses which ultimately may influence brain cascades associated with promotion of neurodegeneration across the lifespan.

KEYWORDS:

• Gut microbiome
• neuro-resilience
• polyphenols
• gut dysbiosis
• neurodegenerative disorders
• parkinson’s disease
• alzheimer’s disease
• probiotics
• synbiotics

Article highlights

• The gut microbiome is responsible for host immune regulation, host metabolism, digestion, vitamin synthesis, neurological development, and energy homeostasis.

• The composition of the microbiome is affected by many factors, such as lifestyle, diet, and environmental toxins.

• Alteration in gut microbiota leads to inflammation, increased oxidative stress, and cellular degeneration and has also been linked to PD, AD, MS, and ALS. The microbiome initiates neurodegeneration through pathways such as the leaky gut mechanism, inflammasome activation, and NF-κB signaling.

• In PD, gut microbiome dysbiosis mediated inflammatory cascades release inflammatory cytokines that may be responsible for disruption of the blood brain barrier allowing inflammatory cytokines to penetrate the brain. Synbiotic metabolites (polyphenols) play a role in the attenuation of proteostasis associated with abnormal misfolding in PD such as protein misfolding of alpha-synuclein (α-syn).

• The gut microbiome plays a role in activating NLRP3 inflammasome, a mediator of innate immunity in microglia in the brain has been associated with destructive neuroinflammatory cascades in AD.

• Altered microbiome with reduced levels of anti-inflammatory bacteria in the gut has been associated with MS and ALS pathogenesis.

• Modulation of the gut microbiome via consumption of prebiotics, probiotics, and synbiotics is associated with improved cognitive abilities and lowered levels of pro-inflammatory cytokines as well as attenuation neurodegenerative symptoms.

Acknowledgments

Figures were created with BioRender.com. The authors thank Kyle J. Trageser for his assistance in editing this manuscript.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by Grant Number P50 AT008661-01 from the NCCIH and the ODS. Dr. Pasinetti holds a Senior VA Career Scientist Award. We acknowledge that the contents of this study do not represent the views of the NCCIH, the ODS, the NIH, the U.S. Department of Veterans Affairs, or the United States Government.