Defining the Parkinson’s Microbiome Strengthens Links to Gut Health

Summary: A meta-analysis study reveals alterations in the gut microbiome may trigger gastrointestinal problems associated with Parkinson’s disease. Additionally, the gastrointestinal problems may occur years before other Parkinson’s symptoms develop.

Source: Quadram Institute

Researchers from the Quadram Institute have carried out a meta-analysis of the gut microbiome in Parkinson’s disease, giving the clearest picture to date of the changes associated with the condition.

By re-analysing data from ten different studies, a common pattern of changes in the abundance of bacteria types in Parkinson’s disease emerges, suggesting that the alteration in the gut microbiome might trigger some of the gastrointestinal problems seen in patients.

Parkinson’s is a progressive condition that affects nerve cells that produce dopamine, which coordinates movement. As more nerve cells die, less dopamine is produced, leading to gradually worsening tremors, slower movement and muscle stiffness.

In addition, many people with Parkinson’s disease have gastrointestinal problems that can show several years before the physical movement symptoms. They may also have inflammation and “leaky” gut, signs of an imbalanced gut microbiome.

These observations have prompted genome sequencing studies to identify the types of bacteria in the microbiome of people with Parkinson’s disease, and compare that with people without the condition.

Several studies have shown differences in the Parkinson’s microbiome, but no clear consensus has emerged. Differences across studies may reflect different methodologies, but also the inherent variability in the human microbiome, shaped by lifestyle and dietary variations in different populations around the world.

Drug treatment regimens and antibiotic usage also impact on gut bacteria, so variability between different studies isn’t a surprise, but it does make drawing definitive conclusions on the association between the microbiome and Parkinson’s harder.

To address this, the Quadram Institute researchers sought to reanalyse the patient data paired with their control collected across studies from six different countries. This large pool of 1200 samples allowed the researches to identify robust differences between the microbiomes of people with or without Parkinson’s disease. The study was supported by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UKRI.

The meta-analysis, published in the journal npj Parkinson’s Disease, confirmed that the Parkinson’s microbiome is different with a reduction in the dominant bacteria usually found in a healthy human gut.

But to understand how changes in the microbiome affect health, we need to know what those bacteria are doing. What chemicals, metabolites or signals do they produce and how does this change with the disease?

The researchers report that some of the depleted bacteria in Parkinson’s produce butyrate, which is used by the cells that line the gut to maintain its integrity as a barrier. Butyrate and other short chain fatty acids also play important roles in interactions between the gut, the nervous system and the brain.

In previous studies, Parkinson’s disease patients were shown to have lower butyrate levels and increased gut lining inflammation and permeability. Similar depletions in key bacterial species, butyrate levels and gut lining integrity are seen in patients with Inflammatory Bowel Disease (IBD) and IBD patients have a 20%-30% higher risk of developing Parkinson’s disease.

Other bacteria involved in methane production are enriched in the gut of Parkinson’s patients. This together with an increased abundance of bacteria able to degrade the mucus within the gut might affect transit time and explain the constipation problems that are recurrently observed in Parkinson’s patients.

This study backs up and adds to the evidence linking the gut microbiome, gut inflammation and immune function in Parkinson’s, and provides intriguing hints into potential mechanisms by which the gut microbiome influences the disease.

This shows a gut and a brain
Meta-analysis provides the clearest picture to date about the Parkinson’s gut microbiome. Credit: Quadram Institute

However, the team underlines that the available data can’t answer the question of whether the microbiome alterations cause Parkinson’s Disease or are an effect of it, and suggest sampling strategies that could help understand the causal link between the disease and the gut microbiome.

Dr Stefano Romano who led the study commented “The variability across studies is very big. However, we can still detect differences between the gut microbiome of patients and controls. This means that microbiome alterations in Parkinson’s disease are consistent across sampling cohorts.”

“There is a clear need to further research gut microbial changes linked to diseases in diagnostic or prognostic applications.”

Microbiome alterations may also be used as biomarkers, especially useful for spotting the earliest onset of the disease, and open new targets for therapies.

“The restoration of a balanced microbiome in patients might alleviate some of the symptoms of Parkinson’s, and this is a really exciting route of research we are exploring.”

About this microbiome and Parkinson’s disease research news

Source: Quadram Institute
Contact: Press Office – Quadram Institute
Image: The image is credited to Quadram Institute

Original Research: Open access.
Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation” by Stefano Romano, George M. Savva, Janis R. Bedarf, Ian G. Charles, Falk Hildebrand & Arjan Narbad. npj Parkinson’s Disease


Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

The gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology.

PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing.

Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts.

We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera LactobacillusAkkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations.

This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

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  1. Numerous metabolites produced by intestinal microbes are considered mitochondrial toxins. First these metabolites can pass through the intestinal wall into the blood stream, secondly they can then pass through the blood brain barrier into the brain and damage the mitochondria of the dopamine producing neurons in an area of the mid brain known as the substantia nigra. When enough mitochondria are damaged the brain cells (Neurons) themselves will begin to die, and when enough of these dopamine producing brain cells die the patient is diagnosed with Parkinson’s disease. It is for this same reason that Migrant farm workers are disproportionatly diagnosed with Parkinson’s disease, they have very high exposure to pesticides, and many pesticides are mitochondrial toxins. So weather the mitochondrial toxin is exogenous from pesticide exposure or endogenous from intestinal dysbiotic metabolite production, the end result can be the same, mitochondrial damage leading to destruction of the dopamine producing neurons in the substantia nigra and subsequent diagnosis with Parkinson’s disease. It is for this reason that any therapeutic intervention needs to include mitochondrial restoration, as well as an antimicrobial and microbiome restoration strategy if causation is determined to be intestinal dysbiosis.

  2. Hi, I was born in 1974 in Indiana and the day I was born I had to go straight to Riley Hospital for Children in Indianapolis and have surgery. I was born as I was told with necterizing enter- colitis. And I was also told I have short gut. I’m at the age where I’m worrying more about it and I think it’s true that your intestines affect your brain and would be glad if you wanted to test me on things so maybe together we can help kids later. Thank you.

  3. My father suffered a peptic ulcer for which he received treatment and went on to later develop Parkinsons. Years before he was poisoned after using commonly available garden insecticide which I always suspected set off a chain of events. A very interesting article.

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