Exploring the connection between Parkinson's disease and gut microbiota to uncover potential therapeutic targets

By Dr. Priyom Bose, Ph.D.Jul 15 2022Reviewed by Danielle Ellis, B.Sc.

One of the most common neurodegenerative diseases affecting more than 10 million individuals worldwide is Parkinson's disease (PD). A PD patient experiences rigidity, tremor, and bradykinesia, along with gastrointestinal dysfunction (e.g., constipation), psychological and behavioral problems, and cognitive impairment. Scientists have published a new review in CNS Neuroscience & Therapeutics, focusing on the relationship between PD and gut microbiota. They believe the connection between PD and gut microbiota could serve as a potential therapeutic target for PD treatment.

Background

Previous studies have shown that PD mostly prevailed in individuals over 50 years. A higher incidence of PD has been reported in males compared to females. Although PD mostly occurs due to environmental factors, including pesticide exposure and dairy intake, other risk factors associated with PD are β2- adrenergic receptor antagonists and traumatic brain injury. In PD patients, the dopaminergic (DA) neurons containing neuromelanin (NM) are damaged, which is present in the substantia nigra (SN) region of the midbrain. 

Clinical symptoms, such as tremors, occur due to the damaged SN-striatum dopamine projection pathway. Previous studies have reported a negative correlation between the intake of nicotine (tobacco), caffeine (coffee), and inflammatory drugs and the incidence of PD. Imaging techniques, such as advanced magnetic resonance imaging (MRI), are used to diagnose PD by detecting the changes in the brain microstructure.

In the last two decades, rapid advancements in high-throughput technology have helped to understand the composition, number, and functional properties of intestinal bacteria. Homeostasis of gut bacteria is essential to maintain the host’s health. Previous studies have shown that gut microbiota changes in the host in accordance with their age, diet, and exercise.

Several studies have shown that intestinal bacteria are related to the pathogenesis of neurodegenerative diseases, such as PD and Alzheimer’s disease. These studies have reported a modification of intestinal microecology in PD patients with diabetes and colitis. Scientists believe that understanding the link between gut bacteria and PD could lead to the discovery of a novel PD treatment.

Gut microbiota and Parkinson’s disease

Research has documented the prevalence of 1000 ubiquitous species in human guts. Mammals share a complex symbiotic relationship with these microbes. For instance, the host produces microRNAs (miRNAs) that translocate and enter bacterial cells. The miRNAs regulate bacterial gene transcripts and alter their growth behavior. miRNAs, such as miRNA-146A, are correlated with the abundance of Listeria. Studies have shown that Firmicutes and Proteobacteria contain a high number of target sites for miRNAs. Previous studies have shown that miRNAs-targeted proteins are associated with the biofilm formation and lipopolysaccharide (LPS) biosynthesis pathways of many pathogenic bacteria linked to PD pathogenesis.

Scientists have reported a significant difference in gut microbiota in PD patients and healthy individuals. Genomic studies have shown intestinal microbiome diversity in PD patients is poor compared to healthy controls. In PD patients, an abundance of bacteria belonging to the Clostridiales family and genus Peptoniphilus was found, and a very low prevalence of genera Faecalibacterium and Fusicatenibacter were observed. 

Intestinal inflammation has been considered an important contributor to the development of PD. Thereby, scientists reported that patients with inflammatory bowel disease (IBD) are at a higher risk of PD incidence. Moreover, a high prevalence of fecal markers of intestinal permeability, i.e., zonulin and antitrypsin, was reported in PD patients.

The gut microbiota is typically associated with hosts’ metabolism and immune regulations. Aging causes significant changes in gut microbiota. This is because aging disrupts the microecological balance and aids in producing pathogenic bacteria. A recent study has reported a lower Simpson index and Equitability Index in PD patients, which indicates gut microbial dysregulation.

Some common pathogens, e.g., Proteus mirabilis, E. coli, and Bacteroides fragilis, produce LPS, a neurotoxin. These neurotoxins are released rapidly with aging and systemically induce inflammatory pathologies and PDs. Some of the common bacteria associated with PD are Helicobacter pyroli, Enterococcus faecalis, and Proteus mirabilis. Additionally, bacteria belonging to the family Bifidobacteriaceae, Ruminococcaceae, Verrucomicrobiaceae, and Christensenellaceae are associated with PD.

Diet plays an important role in the gut microbiome; for instance, a high-fat diet reduces the expression of intestinal tight junction protein and also intensifies the intestinal wall cell permeability by triggering the intracellular protein kinase C signaling pathway. 

Treatment of gut microbiota

The fecal transplantation (FMT) procedure is used to restore the normal bacterial composition of the patients. FMT is commonly used to treat problems associated with Clostridium difficile. Importantly, scientists reported that FMT was effective in the interventional treatment of neurological disorders. Animal studies have shown that regulating gut microbiota by FMT improved intestinal inflammation and reduced depression-like symptoms.

Studies have shown that FMT enhanced Blautia and Prevotella and decreased the population of Bacteroidetes, which resulted in significantly improved non-motor symptoms (e.g., constipation and psychological problems). More clinical studies are required to draw a solid conclusion related to the effectiveness of FMT in PD patients.

Probiotic therapy enhanced oxidative capacity and improved symptoms in IBD patients. Studies have shown that oral probiotics have been beneficial for PD-related symptoms, e.g., depression, and reduced inflammatory factors. Scientists also use antibiotics in low dosages to reduce harmful bacteria in PD patients.