Parkinson's disease is the fastest-growing neurodegenerative disorder worldwide, having more than doubled since 1990 (Lang, 2024). In 2019, its global prevalence was reported to be 8.5 million (Lang, 2024). It is characterised by tremors, stiffness, and a loss of coordination, usually affects people over the age of 60 years, and is 50% more prevalent in men than in women (Lang, 2024). However, each person's experience of Parkinson's disease is different, with over 40 potential symptoms that may present in different ways (Parkinson's UK, 2024).
Vitamin deficiency
A new study led by scientists in Japan analysed the microbiota of people living with Parkinson's, as well as those without, and noted that those with the disease have notably fewer bacterial genes that produce riboflavin (vitamin B2) and biotin (vitamin B7) (Nishiwaki et al, 2024). Both are essential for the metabolisation of carbohydrates, fats and proteins into glucose for energy, as well as having anti-inflammatory effects (Lang, 2024).
Nishiwaki et al investigated the genomes of gut bacteria in 94 people with Parkinson's disease and 73 controls in Japan, using faecal analysis. Shotgun sequencing, which analyses the genetic material in a sample, the authors recorded bacterial genomes, then comparing their results with findings from studies carried out in the USA, Germany, China, and Taiwan.
The lack of the bacterial genes noted was associated with reduced intestinal short-chain fatty acids and polyamines, which are agents that maintain the intestinal barrier and prevent the leakage of toxins into the blood that can then access the brain.
Gut first
Based on the hypothesis that Parkinson's disease may begin in the gut prior to spreading to the brain to produce symptoms, a study published in 2022 examined the role of the gut microbiome in the metagenomics of Parkinson's. It revealed that people living with this disease have an imbalance in gut microbiota, with differences in 30% of bacterial species, genes and pathways being altered compared with healthy individuals. In fact, the species in the gut that were associated with Parkinson's were found to form polymicrobial clusters that grow or shrink together, or even compete.
Wallen et al (2022) carried out a large-scale study including 490 people living with Parkinson's disease, alongside 234 control individuals. They investigated faecal DNA using deep shotgun sequencing. They then carried out metagenome-wide association studies to examine for disease association, using network analysis for identification of polymicrobial clusters, and performing functional profiling.
They concluded that the microbiome associated with Parkinson's disease is disease-permissive, which was found to be validated by an overabundance of pathogens and immunogenic components, dysregulated neuroactive signalling, preponderance of molecules causing alpha-synuclein pathology, and over-production of toxins, in combination with a reduced ability to recover due to the reduction of anti-inflammatory and neuroprotective factors. This research validated the hypothesis that Parkinson's starts in the gut microbiome.
A total of 85 species of gut micro-organism were associated with Parkinson's disease, where each was either increased or decreased in the Parkinson's patient but stable in a healthy patient. In addition to the associations uncovered in the study, Wallen et al established a connection between changes in gut bacteria and a person's response to Parkinson's medication, with some observation of how the medication can influence how fast the disease progresses. For example, a certain bacterium was increased in a Parkinson's patient which was responsible for the breakdown of medication; in this case levodopa, prior to absorption from the gut to the blood stream. This was thought to contribute to a reduced effectiveness of some medication used to treat Parkinson's disease.
Another key area identified was the change in the level of tyrosine. This substance is a molecule that is required to create dopamine, which is the hormone required for movement and for memory. Some of the other types of bacteria that were increased are those that would break tyrosine down before it is absorbed from the diet, thus causing a decrease in the body's ability to make dopamine, which is already present at much lower levels in people with Parkinson's disease.
Other bacteria found were those that help gut agility and the movement of food through the body. The bacteria in short supply, again, were those that were required for a bodily process; in this case, movement through the gut. Therefore, Wallen et al observed that this lack of essential bacteria in the microbiome of a person with Parkinson's may explain why constipation is so common in this patient cohort. Similarly, other bacteria that help to provide neuroprotection were also in short supply in those with Parkinson's disease, suggesting that these bacteria may be linked directly to the cause of the process of neurodegeneration.
Potential ways forward
It is possible that the use of B vitamin therapy may help to address these deficiencies, restoring the barrier and treat Parkinson's disease, though experts warn that these data are too premature to warrant any such therapeutic interventions or changes to clinical practice at present (Nagoya University, 2024).
Following the Wallen et al (2022) study, the American Parkinson Disease Association (APDA) (2023) discussed whether altering the microbiome could be helpful to those living with Parkinson's disease. They discussed the notion of taking probiotics, which have been shown to help with constipation, which is a very common problem experienced by people with Parkinson's disease.
They also raised the idea of antibiotics, but noted that this may be a harmful approach as plenty of good bacteria can be destroyed along with the targeted bacteria, due to the broad spectrum nature of antibiotics. They also brought up the potential use of faecal transplantation, which is a technique where the faecal matter from a healthy person being is transplanted into the gut of a person with Parkinson's disease, in order to change the microbiome to include the healthy bacteria needed. However, this remains a hypothesis that is worth exploring in current and future research.
It is becoming increasingly evident that the gut-first analogy of Parkinson's disease is valid, and new avenues for battling the disease and preventing it altogether can therefore be sought through numerous studies that can now focus on the effect of certain bacterium, and whether dietary changes and other changes to the microbiome can impact on formation of and progression of Parkinson's disease.