New hope for Parkinson’s sufferers

New hope for Parkinsons sufferers
Suvi Mahonen

Suvi Mahonen

Suvi is a journalist whose work has appeared in numerous publications in Australia and overseas

Ron Till, 69, was exhausted. Two years previously he had lost the ability to have a good night’s sleep. He would go to bed early, only to be awoken by his body jerking violently, one of his many symptoms of Parkinson’s disease.

But things changed for the better when he signed up for a novel clinical trial assessing the effectiveness of infrared light therapy for Parkinson’s sufferers.  

“It improved my sleep so much,” said Mr Till, from Mannum, South Australia. Within weeks of the trial starting, which involved applying infrared light therapy to his head and abdomen (three times a week for 12 weeks) he stopped jerking awake. “I got back my two blocks of four-hour sleep, which is like gold to me.”

The results of the trial, which involved 19 participants in NSW and SA, showed that Mr Till was not alone, with most participants demonstrating improvements in Parkinson’s symptoms and signs including gait, balance, cognition and fine motor skills after receiving infrared light therapy.

The trial also examined for, and found, changes in the participants’ gut microbiome, which meant that this was the first known trial worldwide to demonstrate changes in the human gut microbiome following infrared light therapy.

Dr Brian Bicknell, microbiologist and lecturer at the Australian Catholic University, says he had the idea following a brainstorming session with his colleagues in 2016 to discuss why a monkey previously involved in an experiment on Parkinson’s disease, would show improvement in symptoms after receiving infrared light therapy only to its abdomen.

“I suggested it was probably the microbiome,” Dr Bicknell said. “The gut microbiome seems to be incredibly important to our own overall health.”

The Australian study’s microbiome findings, which are being published in The Journal of Photochemistry & Photobiology, B: Biology, offer a potential ray of hope for around 80,000 Australians and 10 million people worldwide who are facing a long, slow decline from a progressive neurodegenerative disease. This number of Parkinson’s sufferers is only expected to increase with the world’s ageing population and the recently hypothesised link between contracting COVID-19 and an increased risk of Parkinson’s disease.

The number of cells in the gut microbiome, which is comprised of all the bacteria, protozoa and fungi that colonise the gastrointestinal tract (GIT), is estimated to be a hundred trillion, which is as many as the number of cells in the rest of our entire body.

There has been increased interest in the gut microbiome in recent years, with dysbiosis (an unbalanced microbiome) being linked to a number of medical disorders, including neurodegenerative disease, cardiovascular disease, asthma, diabetes, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colorectal cancer and obesity.  

There has long been a postulated link between Parkinson’s disease, the gastrointestinal tract and the gut microbiome. The gut microbiome in Parkinson’s patients has been shown to be altered compared to those of the general population. Constipation affects 90 per cent of Parkinson’s sufferers, often preceding the initial diagnosis by many years.

The reason for this link is unknown. However, the prime suspect is a protein known as alpha-synuclein. Abnormal accumulations of this protein in nerve cells form microscopically visible lesions known as Lewy bodies which are associated with a decreased ability to repair the DNA damage and increased cell death.

Lewy bodies have been detected in the GIT up to 20 years before the diagnosis of Parkinson’s disease. They are also present in high numbers in the brain of Parkinson’s patients, especially in the basal ganglia.

It is hypothesised that inflammation leads to increased alpha synuclein accumulation in the GIT, with some of this excess being transported to the brain via the vagus nerve. This hypothesis is supported by the fact that those who have undergone a surgical transection of the vagus nerve are less likely to develop Parkinson’s disease.

Improvements in the gut microbiome may reduce GIT inflammation and permeability, thereby reducing alpha-synuclein transportation to the brain, as well as increasing beneficial microbial metabolic byproducts such as serotonin, GABA and dopamine, thereby reducing the risk of Parkinson’s disease and improving symptoms in those who already have the disease.

There is even recent epidemiological evidence that antibiotic usage may increase the risk of developing Parkinson’s disease, by altering the gut microbiome.

In a retrospective study, published in the journal Movement Disorders last year, researchers from the Department of Neurology at the Helsinki University Hospital, compared oral antibiotic usage in Parkinson’s disease patients with randomly selected controls. Soberingly, a statistically significant increased risk of Parkinson’s disease was found in those who had taken antianaerobic or tetracycline antibiotics 10-15 years before, antifungals one-to-10 years before, and/or trimethoprim or sulphonamide antibiotics one-to-five years before their initial diagnosis with Parkinson’s disease.  

Australasian Research Institute’s Dr Ann Liebert and her colleagues had already found that the gut microbiome of mice could be altered through administration of infrared light therapy and wanted to see if this finding could be replicated in humans.

The 19 volunteers were aged between 60 and 80 and had mild to moderate symptoms of Parkinson’s. The participants gave a faecal sample to researchers before the trial began, and were asked not to alter their dietary habits or day-to-day activities during the study. They were then given infrared light therapy via laser devices to their abdomen at a wavelength of 904-nanometres, and to their head at a wavelength of 810-nanometres and/or their neck at a wavelength of 904-nanometres, three times a week for twelve weeks. After three months, a further faecal sample was collected from each participant, and the microbiome from each of the samples were analysed via DNA extraction and testing.

“It was incredibly exciting to see changes in the microbiome and improvements in symptoms happening at the same time,” Dr Liebert said. “(We were) even more excited when we saw the same kind of changes in the Sydney trial where we treated the abdomen only.”

Most participants showed a significant increase (defined as at least a log2-fold change) in 10 different genera of microorganisms including Bacteroides, Alistipes and Prevotella and a significant decrease in 17 different genera including Bifidobacterium, Streptococcus and various Clostridium and Enterococcaceae genera.

Interestingly, two of the bacterium that showed an increase – Bacteroides and Prevotella – have been shown in multiple studies to be reduced in the gut microbiome of Parkinson’s sufferers. In fact, low levels of Prevotella is so strongly associated with a more rapid progression and greater severity of Parkinson’s that is has been proposed as a biomarker for the disease. And Bacteroides is considered beneficial to the microbiome through its anti-inflammatory properties and production of healthy short chain fatty acids.

Five of the bacteria that showed a decrease post light therapy – Bifidobacterium, Streptococcus, Lactobacillus, Christensenella and Enterococcaceae – have been shown in multiple studies to be increased in the microbiome of Parkinson’s sufferers.

Several of the bacteria are generally considered detrimental to the microbiome. Enterobacteriaceae is thought to decrease gut integrity and produce pro-inflammatory metabolites; Clostridium genera are associated with high fat diets and Type 2 diabetes; and Streptococcus is considered to be potentially pathogenic.

“It is quite possible that laser will provide a synergistic effect to the currently available therapeutic manoeuvres [to the gut microbiome],” Professor of Cardiology at Macquarie University, Hosen Kiat, said. “It is a no-brainer if it is useful because it is relatively cheap, it is non-invasive and it has zero side effects.”

Not all the microbiome findings, however, were as expected. Both Lactobacillus and Bifidobacterium are considered beneficial to the microbiome, yet both bacteria showed a significant decrease in most participants following light therapy.

“We know that very few diseases have a magic bullet treatment,” Prof Kiat said. “But if I were a Parkinson’s patient, I would seek out the laser and I would use the same protocol as we described.”

One participant Margaret Jarrett, 75, is convinced of light therapy’s benefits. As an avid flower gardener at her home in Adelaide, she was dismayed when she developed anosmia (loss of smell) due to her Parkinson’s disease. After several weeks of therapy, however, she regained her sense of smell. “It’s amazing, you go outside and I suddenly smell the perfume of murraya in full bloom,” Mrs Jarrett said.

Interestingly, two bacteria that have been found to be elevated in IBS, Dorea and Enterococcaceae, were found to be decreased post light therapy in Dr Liebert’s trial.

It is impossible at this stage to know whether the improvements in the trial participants were due to the effect of infrared light therapy to the brain, or due to changes in the gut microbiome, or partially due to a placebo effect, or, most likely, a combination of all of these things.

But what is certain is that exposure to light therapy did alter the gut microbiome, seemingly for the better.

 

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