Scientists discover gut bacteria is associated with chronic pain

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People with fibromyalgia have differences in their microbiome compared to healthy people, a Montreal research team finds.

Scientists at Université de Montréal and McGill University have found a correlation between fibromyalgia, a disease involving chronic pain, and alterations in the gut microbiome.

Fibromyalgia affects two to four per cent of the population and has no known cure. Symptoms include fatigue, impaired sleep and cognitive difficulties, but the disease is most clearly characterized by chronic pain.

In a new paper published in the journal Pain, McGill and UdeM researchers show, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia.

Approximately 20 different species of bacteria were found in either greater or lesser quantities in the microbiomes of those suffering from the disease than in the healthy control group the scientists studied.

"Bacteria comprising the gut microbiome are hard to observe accurately and vary extraordinarily between people," said co-Nicholas Brereton, a researcher at UdeM's Plant Biology Research who co-authored the study.

"This research navigates that natural variation to reveal specific species of bacteria which were associated with fibromyalgia patients for the first time using metagenomics and machine-learning technologies."

He added: "What we’re so excited about is that, in addition to shedding new light upon the complexity of the gut environment, these findings open up a whole new avenue for discovery in the physiology underpinning chronic pain."  

A range of techniques

Nicholas Brereton

Credit: Amélie Philibert

Researchers led by Amir Minerbi of the McGill University Health Centre's Alan Edwards Pain Management Unit used a range of techniques, including artificial intelligence, to rule out other contributing factors.

They wanted to "confirm that the changes we saw in the microbiomes of fibromyalgia patients were not caused by factors such as diet, medication, physical activity, age and so on, which are known to affect the microbiome," said Minerbi, the study's first author.

“We found that fibromyalgia and the symptoms of fibromyalgia – pain, fatigue, and cognitive difficulties - contribute more than any of the other factors to the variations we see in the microbiomes of those with the disease," he said.

"We also saw that the severity of a patient’s symptoms was directly correlated with an increased presence or a more pronounced absence of certain bacteria – something which has never been reported before.”

Simply markers of disease?

At this point, it’s not clear whether the changes in gut bacteria seen in patients with fibromyalgia are simply markers of the disease or whether they play a role in causing it, the researcher said.

Because the disease involves a cluster of symptoms, and not simply pain, their next step will be to investigate whether there are similar changes in the gut microbiome in other high-pain conditions such as lower back pain, headaches, and neuropathic pain.

The researchers are also interested in exploring whether bacteria play a causal role in the development of pain and fibromyalgia – and whether those bacteria could eventually help in finding a cure, as well as speed up the process of diagnosis.

Difficult to diagnose

Fibromyalgia is difficult to diagnose. Patients can wait as long as four to five years to find out they have it. But this may be about to change, thanks to the new research, done with the help of of other McGill scientists.

"We sorted through large amounts of data, identifying 19 species [of bacteria] that either increased or decreased in individuals with fibromyalgia," said McGill geneticist Emmanuel Gonzalez, of the Canadian Center for Computational Genomics.

"By using machine learning, our computer was able to make a diagnosis of fibromyalgia based only on the composition of the microbiome, with an accuracy of 87 per cent. As we build on this first discovery with more research we hope to improve upon this accuracy, potentially creating a step-change in diagnosis."

“People with fibromyalgia suffer not only from the symptoms of their disease but also from the difficulty of family, friends and medical teams to comprehend their symptoms,” added the study's senior author Yoram Shir, of the MUHC's pain management unit.

"As pain physicians, we are frustrated by our inability to help, and this frustration is a good fuel for research. This is the first evidence, at least in humans, that the microbiome could have an effect on diffuse pain and we really need new ways to look at chronic pain.”

77 patients studied

The research was done on a cohort of 156 people in the Montreal area, 77 of whom suffer from fibromyalgia.  They were interviewed and gave stool, blood, saliva and urine samples, which were then compared with those of the healthy control subjects.

Some of the control subjects lived in the same house as the fibromyalgia patients or were their parents, offspring or siblings.

The researchers’ next steps will be to see whether they get similar results in another cohort, perhaps in a different part of the world, and to do studies in animals to discover whether changes in bacteria play a role in the development of the disease.

About this study

"Altered microbiome composition in individuals with fibromyalgia” by Amir Minerbi, Nicholas Brereton et al was published June 19, 2019, in Pain. The research was funded by the Louise and Alan Edwards Foundation and the Israeli Society for Musculoskeletal Medicine.

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