By Clare Fleishman, MS, RD, for the International Probiotics Association
“The hope is that restoration of the gut microbiome in patients with Parkinson’s disease (PD) may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.” —Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation
Parkinson’s disease (PD) is a debilitating and progressive neuromotor disorder of the central nervous system (CNS) affecting as many as 10 million people across the globe. Bradykinesia (slow movement), tremor, and rigidity are the classic symptoms defining PD. Notably patients also have gut and psychiatric issues, often preceding the clinical diagnosis—sometimes by decades.
Gut-brain axis: Clues to microbiome effect in Parkinson’s disease
Discovery of the complex relationship between the gut microbiome, the enteric nervous system (ENS), and the CNS has recently opened the door to using probiotics to modify the microbiota in PD treatment. For many years, the cornerstone treatment has been levodopa-carbidopa, which increases dopamine levels in the brain. Unfortunately, while the medications may relieve symptoms, they cannot alter the natural history of the disease.
First, take a look at the known evidence on PD that is also the basis for the research into the microbial angle.
Parkinson’s disease has two chief expressions:
Importantly, this latter amassing occurs not only in the basal ganglia but also in the gut. Two modalities, both linked to microbial imbalance, favor α-syn aggregation: Peripheral immune activation and reactive oxygen species (ROS) production. Both neuroinflammation and ROS may favor α-syn aggregation, which may in turn increase pro-inflammatory cytokines and oxidative stress, thus triggering a vicious circle.
The multiple factors associated with the pathogenesis and progression of PD are summarized in this excellent table.
Gut microbe and Parkinson’s disease links
According to seminal work known as the Braak hypothesis, the α-synuclein misfolding may begin in the gut and spread “prion-like” via the vagus nerve into the lower brainstem and ultimately to the midbrain.
As mentioned, researchers now know that gut problems (constipation, dysphagia, altered gut microbiota and leaky gut) exist in PD patients years before diagnosis. Some of the first studies to explore the relation between gut dysbiosis and PD were conducted by Filip Scheperjans and his colleagues in Finland.
Gut dysbiosis also leads to an altered ratio of short-chain fatty acids (SCFA), especially butyrate, as well as altered microglial signaling in the brain leading to disease development and the appearance of PD-associated motor symptoms.
More evidence of the gut microbe and PD link
- Impairment of gastric mobility with an increased dopaminergic content and overexpression of dopaminergic receptors in the stomach.
- Increased intestinal permeability: The gut has its own nervous system comprised of glial cells and neurons. Any overstimulation of the innate immune system due to gut dysbiosis along with “leaky gut” may provoke local and systemic inflammation, leading to enteric neuroglial activation and triggering of α-synuclein pathology. One important study showed an increase in intestinal permeability in PD patients, supporting the hypothesis that PD may be triggered by an unknown agent that breaches the intestinal epithelial barrier to induce α-synuclein aggregation.
- Increased levels of pro-inflammatory cytokines such as IL-6 and TNF-α have been observed in the cerebrospinal fluid of patients with PD.
- Direct correlation between gut bacterial count and disease progression was found in PD patients.
- Different composition of gut microbiota in PD compared to healthy subjects. Microbial species harvested from PD patients showed lower levels of Prevotella, Lactobacillus, Peptostreptococcus, and Butyricicoccus spp. and an increase in Proteus and Enterobacter spp. compared to healthy controls. And in Japanese studies, low counts of Bacteroides fragilis and lower counts of Bifidobacterium were linked to worsening of symptoms.
- As PD advances clinically, PD patients are predisposed to small intestinal bacterial overgrowth (SIBO) which may impair levodopa absorption leading to worsening of symptoms.
- Interestingly, levels of levodopa in PD patients are reduced by abundance of gut bacterial tyrosine decarboxylase (TDC), an enzyme which converts levodopa to dopamine in the gut. TDC genes have been detected in the genome of numerous bacterial species within the genera Lactobacillus and Enterococcus, which are reduced in PD patients.
Potential for probiotic impact
These remarkable observations have inspired several studies intended to evaluate a modulatory role for customized probiotics in patients with PD.
In one recent random controlled study with 120 patients, fermented milk containing prebiotic fiber and multistrain probiotics resulted in a higher increase in the number of complete bowel movements in the group on probiotics.
A 2019 trial revealed that probiotics led to a reduction in clinical symptoms in patients with PD.
Another recent study from Italy looked at the effects of six probiotic strains on 40 PD patients’ blood as well as the same number of healthy controls. Patients were followed-up regularly at the Movement Disorder Center of Maggiore Hospital in Novara, Italy. Researchers assessed cytokine and reactive oxygen species (ROS) release by peripheral blood mononuclear cells (PBMCs), and restoration of artificial membrane permeability.
Probiotics (particularly strains of Lactobacillus salivarius and Lactobacillus acidophilus) modulated not only inflammation through cytokines production but also oxidative damage through a down-modulation of ROS. All the tested probiotic strains restored in vitro epithelial damage. Finally, the tested probiotic strains inhibited pathogens often detected in blood cultures of septic PD patients.
Altogether, these findings suggest a potential role for probiotic strains in modulating inflammation and oxidative stress and protecting the epithelium from gut permeability.
The results are very preliminary still. However, it is never a bad idea to include fiber and fermented foods (possibly probiotic) daily in your diet: kombucha, kefir, yogurt, sauerkraut or fermented vegetables. Add a high-dose multi-strain probiotic daily after breakfast.
Parkinson’s and nutrition: recommended articles and guidelines
Note: The views and opinions expressed here are those of the author(s) and contributor(s) and do not necessarily reflect those of the publisher and editors of WholeFoods Magazine. Information in this article is intended for educational and scientific purposes only. It is not intended as medical or nutritional advice for the treatment or prevention of disease. For medical advice, consult a health care practitioner.
Clare Fleishman RDN, MS is a Registered Dietitian with the Academy of Nutrition and Dietetics and holds a master degree in nutrition science. She bridges the gap between science and health across most platforms: major newspapers, magazines, books (Globesity), workshops, social media and websites. From corporate whiteboards to refugee schools in Egypt, Fleishman agitates for personal and public change. In 2010, she launched www.ProbioticsNow.com to share the cascade of new discovery in the microbiome. Always amazed at this “forgotten organ” Fleishman also creates white papers, blogs, videos and social media for the International Probiotics Association as well as continuing education platforms.
Probiotics have diﬀerent characteristics, qualities and actions that are unique to the speciﬁc strain or combinations. The label should identify the genus, species and strain for each microorganism in the product (i.e. Lactobacillus acidophilus IPA001). If a claim pertaining to individual strains or a blend of strains contained in the product is made, the manufacturer should maintain evidence that the amount(s) provided in the product is consistent with the scientific evidence in support of the claim.