Significant changes in the gut microbiota occur in the earliest stages of Parkinson's disease, and a new study shows these can start before the onset of symptoms.

Narrowing down the culprits in our gut bacteria may lead to earlier diagnosis and also aid in developing targeted treatments for the debilitating disorder.

Researchers from China and Germany looked at the bacteria in the guts of people with early Parkinson's disease, people with REM sleep behavior disorder (RBD), their close relatives, and healthy people.

Similar bacterial changes were observed in the guts of people with RBD and those with Parkinson's disease, with some beneficial bacteria being depleted and some harmful bacteria becoming more abundant. People who were closely related to those with RBD showed the same changes.

Neurologist Bei Huang from the Chinese University of Hong Kong and colleagues also identified 12 potential biomarkers that could help distinguish people with RBD from healthy individuals.

Alpha-synuclein proteins are involved in signaling in healthy nerve cells, but we know that in Parkinson's they form fibrous clumps that harm tissues, leading to symptoms like loss of motor control and tremors. Evidence from animal studies suggests this process starts in the gut and then moves to the brain.

"Given that enteric alpha-synuclein pathology and enteric nervous system dysfunctions, especially constipation, could occur decades before the onset of Parkinson's disease, it is critical to understand gut microbiota and host–microbiome interactions," the researchers write in their published paper.

Up to 20 years before a patient develops Parkinson's they can have subtle problems with their senses, muscles, and minds. One predictor is sleep disorders, particularly RBD. Parkinson's disease, or a related disorder such as multiple system atrophy or dementia with Lewy bodies, eventually manifests in the vast majority of RBD patients.

"REM sleep behavior disorder (RBD) is perceived as the most specific prodromal marker of Parkinson's disease," the authors write. "In addition, a prodromal stage of RBD has been increasingly recognized, underscoring the importance of studying gut microbiota at an even earlier prodromal stage."

A recent study found some of the features of RBD in close family members of RBD patients, along with digestive issues, suggesting that these individuals could be harboring gut bacteria changes. So scientists considered whether these relatives could be key to investigating the extremely early stages of Parkinson's disease.

To find out, the researchers behind this latest investigation analyzed stool samples from 441 people in Hong Kong. They included people with RBD, or a family history of the disease, people who had Parkinson's disease with motor symptoms for less than 5 years, and healthy people for comparison.

They found 84 families and 249 genera of bacteria and compared the diversity of bacteria present between the four different groups of people.

The analysis controlled for factors that could affect the results; functional constipation (difficulty having bowel movements) was more common in early Parkinson's disease patients than in those without the disease, as were certain medications.

The composition of gut bacteria in the early Parkinson's disease group was significantly different from the control group. And the RBD group's bacterial composition was similar to the early Parkinson's disease group but different from the control and RBD relatives groups.

These changes included a decrease in bacteria that produce short-chain fatty acids (SCFA), which maintain the gut barrier and have anti-inflammatory properties. Their depletion may lead to higher intestinal permeability and subsequent aggregation of alpha-synuclein in the gut.

Another observation was a progressive increase in Collinsella bacteria across groups from control, to relatives of RBD, to RBD patients to Parkinson's disease. This pro-inflammatory bacteria can contribute to making the gut more permeable. It's also been linked to Alzheimer's and other neurological disorders.

Huang and team then used machine learning to make predictions about potential biomarkers for RBD. After removing less common and less abundant bacteria, 36 families and 88 genera were left, which were narrowed down to 12 that appeared in 60 percent or more of RBD computer models.

They also calculated likelihood ratio, a research criterion to identify people at risk of prodromal Parkinson's disease. RBD patients were more at risk than their family members or healthy controls.

The study has limitations, it's a small sample size and a cross-sectional study, which doesn't prove cause and effect. The groups with RBD or Parkinson's disease and the control groups had more men and were, on average, older than the group of relatives of RBD patients.

But it's important research as early diagnosis is a major challenge in the fight against Parkinson's disease. Sadly most people have lost between 60 and 80 percent of dopamine-producing neurons in their brain stem by the time they are diagnosed with the disease.

The World Health Organization estimates that over 8.5 million people have Parkinson's, the second most common neurodegenerative disease after Alzheimer's.

"In summary," the researchers write, "gut dysbiosis are already present at a much earlier stage, preceding the onset of RBD and Parkinson's disease, which emphasizes the potential role of gut microbiota".

Future studies could investigate factors like gut metabolism and inflammatory markers to increase scientists' understanding.

The research has been published in Nature Communications.