Longevity Briefs: Could Vitamin B Supplements Prevent Parkinson’s Disease?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

A key characteristic of Parkinson’s disease is the accumulation of a protein called α-synuclein, forming clumps in the brain known as Lewy bodies. Yet these Lewy bodies aren’t just found in the brain, but also in other tissues including the gut. There is also a well established link between Parkinson’s disease and constipation, which can precede the actual diagnosis of Parkinson’s disease by many years. This has led to the “Braak hypothesis,” which theorises that Parkinson’s disease might originate in the gut or nose and then spread through the nervous system into the brain.

For many years, researchers studying Parkinson’s have been trying to understand the precise role of the gut microbiome – the community of bacteria and other microorganisms living in our intestines. The composition of the gut microbiome appears to have a surprisingly large effect on both the immune system and the central nervous system, and we know that microbiome composition changes with age. We also know that it is possible to restore an ‘aged’ microbiome to a younger state by transplanting gut bacteria from a younger individual in the form of a faecal microbiota transplant. However, we still don’t have a good understanding about how and which specific gut microbes are important for ageing and disease. In this study, researchers identify features of the microbiome in Parkinson’s disease patients that are common across various countries.

The discovery:

Researchers discovered that Parkinson’s disease is associated with reduced production of vitamin B by gut bacteria, potentially contributing to the disease by making the gut more permeable.

The researchers used advanced techniques like shotgun metagenomic sequencing (which sequences all DNA in a sample to identify all microorganisms and their genes) and metabolomic assays (to measure substances manufactured by gut microbes, like short-chain fatty acids and polyamines) in order to paint an overall picture of microbiome composition and function. They applied these techniques to a sample of 94 Parkinson’s patients and 73 healthy controls from Japan, and combined this data with similar previously published datasets from the USA, Germany, China and Taiwan. This brought the total size of the dataset to 813 Parkinson’s patients and 558 controls.

They found that the α-diversity (a measure of the overall diversity of gut bacteria) was consistently increased in Parkinson’s patients across all six datasets compared to the controls. Specific bacteria like Akkermansia muciniphila were increased in Parkinson’s, while Roseburia intestinalis and Faecalibacterium prausnitzii were decreased. There was also a significant decrease in the overall activity of genes involved in the production of essential vitamins B2 and B7 and an apparent reduction in carbohydrate-processing enzymes by bacteria in Parkinson’s patients. This decrease in vitamin B production in Parkinson’s disease was associated with a reduction in short-chain fatty acids (SCFAs) – beneficial compounds produced by gut bacteria.

The researchers also found that the specific bacteria associated with decreased vitamin synthesis differed between Asian and Western countries, suggesting that the microbiome changes associated with reduced vitamin B production in Parkinson’s differ across the world.

The implications:

While this study doesn’t prove that changes in microbiome composition or vitamin B production contribute to Parkinson’s disease, the researchers suggest a compelling mechanism. Several B vitamins are involved in the production of SCFAs and polyamines by bacteria, and these products are in turn important for maintaining intestinal mucus layer. A thinning of this layer results in increased intestinal permeability, which could then expose the nervous system to harmful compounds that would usually remain in the gut. SCFAs and polyamines also play a role in regulating immune responses, so their deficiency could contribute to neuroinflammation (inflammation in the brain). There are already some early studies suggesting that vitamin B3 (niacin) supplementation may improve motor symptoms in Parkinson’s patients, though this vitamin may be working through a different mechanism than the one proposed above. In any case, investigating the effects of vitamin B2 and B7, or attempting to address the root cause by targeting the bacteria that produce them, could prove valuable.

An interesting observation from this study was that α-diversity was increased in Parkinson’s patients. This runs contrary to the prevailing view that less diversity is associated with ageing, poorer gut health and increased disease risk, and highlights how we still don’t really understand the microbiome’s role in health particularly well. What actually matters for health probably has more to do with the specific types of bacteria present and how those bacteria are interacting with the immune system, diet and other environmental factors.