Advancing Parkinson's treatment via microbiome research
Key Takeaways
The role of gut microbiota in Parkinson's disease (PD) includes imbalances like decreased presence of anti-inflammatory bacteria and increased proinflammatory strains, which could influence neurological health.
Therapeutic approaches for PD are evolving, focusing on probiotics, fecal microbiota transplants, and dietary interventions to manage symptoms and improve gut-brain axis function.
Further research is needed on the causal relationship between gut dysbiosis and PD, and physicians should remain open to novel therapeutic strategies targeting the gut microbiota. Collaborating with gastroenterologists and nutritionists could enhance patient care by integrating these approaches into multidisciplinary treatment plans.
Parkinson's disease (PD) is second only to Alzheimer's in prevalence among neurodegenerative disorders, and it is increasing the fastest worldwide—the number of people with PD is expected to double in the next 20 years, according to authors of a review in Frontiers in Cellular and Infection Microbiology.[]
While PD is diagnosed clinically, by the combination of bradykinesia, resting tremor, and rigidity, the true hallmark of PD is the presence of Lewy bodies, composed mainly of alpha-synuclein aggregates, in the substantia nigra's dopaminergic neurons and other brain areas.
The gut-brain axis
PD is often preceded by a prodromal stage, characterized by the emergence of non-motor symptoms due to the accumulation of alpha-synuclein gastrointestinal symptoms (seen in more than 60% of cases), which can precede motor dysfunction by a decade.
The Frontiers in Cellular and Infection Microbiology authors stated, “Sixty-one percent of patients with PD report gastrointestinal-related symptoms such as sialorrhea, dysphagia, nausea, vomiting, early satiety, constipation, bloating, gastroparesis, and colonic dysmotility.”
The connection between gut microbiota and the central nervous system (CNS) is in the spotlight due to its role in neurological diseases like Alzheimer's and PD. The gut-brain axis, a bidirectional communication pathway, allows gut microbiota to influence CNS function.
The intricate gut microbiota ecosystem is comprised of diverse bacterial populations like Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, as discussed in a 2024 review in Nutrients.[]
Age, hormones, diet, medication, physical activity, and environmental exposures influence gut microbiome diversity. A balanced gut microbiota maintains the body’s homeostasis, enhances gut-barrier function, and metabolizes nutrients, drugs, and xenobiotics.
Some gut microbes also produce short-chain fatty acids (SCFAs), which help diminish systemic inflammation.
Microbiome dysbiosis
“Some of the most significant ways that gut microbes can interact with the central nervous system include the synthesis of neurotransmitters (acetylcholine, catecholamines, gamma-aminobutyric acid, histamine, and serotonin), immune system activity modulation, the synthesis of specific metabolites, effects on tryptophan metabolism, alterations in the microbiota’s composition, and nerve connections,” the Nutrients authors wrote. The enteric nervous system (ENS) also influences the gut-brain axis via the vagus nerve.
Gut microbial imbalance leads to increased intestinal permeability, fostering a pro-inflammatory state.
This phenomenon, often termed "leaky gut," could result in the unregulated passage of inflammatory mediators, bacterial components, and toxic metabolites into the systemic circulation that can break the blood-brain barrier and lead to neuroinflammation.
Recent meta-analyses reveal the following gut microbiome abnormalities in PD patients:[][]
Reduced anti-inflammatory SCFA-producers (Lachnospiraceae, Faecalibacterium, Prevotellacea)
Increased proinflammatory bacteria (Verrucomicrobiaceae, Christensenellaceae)
Elevated Akkermansia bacteria associated with weakened gut barriers and increased nervous system susceptibility to pathogens
Therapeutic approaches
Probiotics
Research, including randomized controlled trials and a 2023 meta-analysis published in Frontiers in Pharmacology, has observed that probiotics or prebiotics, namely Lactobacillus, Bifidobacterium, Bacillus, and Fructooligosaccharides, can improve bowel function and reduce inflammation in patients with PD.[]
These probiotics can be given to patients as yogurt, capsules, tablets, or in powder form.
Fecal microbiota transplant (FMT)
FMT involves the transfer of healthy microbiota to a dysbiotic gut. Animal studies have demonstrated its effectiveness in reversing symptoms of Parkinsonism, according to the Frontiers in Cellular and Infection Microbiology authors. Human studies, though limited, suggest potential benefits in improving motor and non-motor symptoms, albeit with some safety concerns requiring further investigation.
Dietary interventions
Dietary interventions offer potential therapeutic options for managing neurodegenerative diseases. Diets like the ketogenic diet (KD), Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), and Dietary Approaches to Stop Hypertension (DASH) have shown promise in mitigating neurodegeneration noted in PD.
The KD, noted for its high fat and low carbohydrate content, has been used in other neurological disorders like epilepsy, and in small studies it was found to help reduce cognitive decline in some types of dementia. The Mediterranean diet, rich in anti-inflammatory components like omega-3 fatty acids and polyphenols, also has the potential to reduce cognitive decline.
The interplay between diet, gut microbiota, and neurodegenerative diseases highlights the potential of dietary and microbial interventions in managing PD.
What this means for you
Without prospective studies, it is very challenging to determine whether changes in gut microbiota cause, contribute to, or are simply a downstream effect of PD—and we do not yet know whether deliberate changes in gut microbiota can prevent, treat the symptoms of, or slow the disease process in PD. Still, targeting the gut microbiota presents a promising approach to understanding and treating PD. While the exact role of gut dysbiosis in PD's etiology remains unclear, it may offer novel therapeutic strategies. In patients with an early risk of PD, careful introduction of interventions like probiotics and dietary modifications could potentially improve outcomes through regulation of the gut-brain axis.