A probiotic bacterium called Lacticaseibacillus rhamnosus HA-114 prevents neurodegeneration in the worm C. elegans, an animal model used to study amyotrophic lateral sclerosis (ALS).
That’s the finding of a new study at Canada’s CHUM Research Center (CRCHUM) led by Université de Montréal neuroscience professor Alex Parker and published in the journal Communications Biology.
He and his team suggest that disruption of lipid metabolism contributes to this brain degeneration and show that the neuroprotection provided by HA-114, a non-commercial probiotic, is unique compared to other strains of the same bacterial family tested.
“When we add it to the diet of our animal model, we see that it suppresses the progression of motor neuron degeneration,” said Parker, the study’s lead author. “The particularity of HA-114 resides in its fatty acid content.”
By allowing signals to be transmitted to muscles to contract, motor neurons, which are nerve cells, allow us to move our bodies at will.
People with ALS see a gradual deterioration of their motor neurons. This causes them to lose their muscle capacity, to the point of total paralysis, with an average life expectancy of only 3 to 5 years after diagnosis.
Almost 3,000 people in Canada have ALS.
“Recent research has shown that disruption of the gut microbiota is likely involved in the onset and progression of many incurable neurodegenerative diseases, including ALS,” Parker explained.
The identification of neuroprotective bacterial strains could form a basis for new therapies.
A matter of diet
At the center of this scientific project is Audrey Labarre, the study’s first author, a postdoctoral fellow working hard to advance ALS research by focusing on motor neuron degeneration in C. elegans worms .
Measuring just one millimeter in length and sharing 60 percent of their genetic makeup with humans, these nematodes were genetically modified with genes associated with ALS for CRCHUM research.
To study the neuroprotective effects of a probiotic-based dietary supplement in this animal model, Labarre tested a total of 13 different bacterial strains and three combinations of strains.
The HA-114 stood out from the group. The action of the probiotic helped reduce motor disorders in models with ALS and also Huntington’s disease, another neurodegenerative disease.
Two genes at play
Based on data from the genetic study, genomic profiling, behavioral analysis and microscopy images, the scientific team identified two genes, acdh-1 and acs-20, that play a key role in this neuroprotective mechanism.
They were able to carry out this meticulous work thanks to the collaborations with Martine Tétreault, researcher at the CRCHUM, and Matthieu Ruiz, researcher at the Research Center of the Montreal Heart Institute.
Existing in equivalent forms in humans, both genes are involved in lipid metabolism and beta-oxidation, a process by which fatty acids are broken down into energy in the mitochondria, the true powerhouses of the cell.
“We believe that the fatty acids supplied by HA-114 enter the mitochondria through an independent and non-traditional pathway, said Parker. In doing so, they restore the balance of the impaired energy metabolism in ALS and lead to to a decrease in neurodegeneration.”
The researcher’s team is now conducting similar studies on a more complex animal model than the C. elegans worm: the mouse.
They will then validate in a clinical setting whether HA-114 could be a therapeutic adjunct to current ALS treatments. The advantage is that probiotics, unlike drugs, produce few side effects, they say.
To this end, a Canada-wide clinical study based at the CRCHUM and led by the director of the ALS clinic, Dr. Geneviève Matte, will be conducted with 100 subjects beginning in spring 2023.