Protective probiotic for ALS found
Abstract: Lacticaseibacillus rhamnosus HA-114, a non-commercial probiotic reduces neurodegeneration and has neuroprotective effects in laboratory models of ALS.
Source: University of Montreal
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).
This is the finding of a new study at the Canadian Research Center CHUM (CRCHUM) led by Alex Parker, professor of neuroscience at the University of Montreal, which was published in the journal Communication biology.
He and his team suggest that disruption of lipid metabolism contributes to this cerebral degeneration and show that the neuroprotection afforded by HA-114, a non-commercial probiotic, is unique compared to other tested strains of the same bacterial family.
“When we added it to the diet of our animal model, we observed that it suppressed the progression of motor neuron degeneration,” said Parker, lead author of the study. “The specialty of HA-114 lies in its fatty acid content.”
By enabling 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. As a result, they lose muscle function, to the point of complete paralysis, with an average lifespan 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.
Identifying neuroprotective bacterial strains could provide the 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 who works hard to advance ALS research by focusing on motor neuron degeneration in the worm C. elegans.
Measuring just one millimeter in length and sharing 60% of their genetic structure with humans, these nematodes were genetically modified with ALS-related genes 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 pack. The action of probiotics helped reduce motor disorders in models with ALS and Huntington’s disease, another neurodegenerative disease.
Two genes at play
Using data from a genetic study, genomic profiling, behavioral analysis, and microscopic imaging, the research 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 collaboration with Martine Tétreault, researcher at CRCHUM, and Matthieu Ruiz, researcher at the Montreal Heart Institute research center.
Existing in equivalent forms in humans, both genes are involved in lipid metabolism and beta-oxidation, the process through which fatty acids are broken down into energy in the mitochondria, the true cellular powerhouses.
“We believe that the fatty acids delivered by HA-114 enter the mitochondria through an independent, non-traditional pathway,” Parker said. In doing so, they restore balance to the impaired energy metabolism in ALS and lead to a reduction in neurodegeneration.”
A team of researchers is now conducting similar studies in an animal model more complex than the C. elegans worm: the mouse.
See also
They will then confirm in a clinical setting whether HA-114 can be a therapeutic adjunct to current ALS treatment. The advantage is that probiotics, unlike drugs, produce few side effects, they say.
To that end, a Canada-wide clinical study based at CRCHUM, led by ALS Clinic Director Dr. Geneviève Matte, will be conducted with 100 subjects, starting in the spring of 2023.
About this ALS research news
Author: Bruno Geoffroy
Source: University of Montreal
Contact: Bruno Geoffroy – University of Montreal
Picture: The image is attributed to the researchers
Original research: Open access.
“Fatty acids obtained from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-related neurodegeneration” Audrey Labarre et al. Communication biology
Abstract
Fatty acids obtained from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-related neurodegeneration
The human microbiota is believed to influence health. Microbiome dysbiosis may be associated with neurological conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis and Huntington’s disease. We report the ability of a probiotic bacterial strain to arrest neurodegeneration phenotypes.
We show it Lacticaseibacillus rhamnosus HA-114 is neuroprotective in C. elegans models of amyotrophic lateral sclerosis and Huntington’s disease. Our results show that neuroprotection from L. rhamnosus The HA-114 is unique from the rest L. rhamnosus strains and is found in its fatty acid content.
Neuroprotection by L. rhamnosus HA-114 requires acdh-1/ACADSB, cat-1/ACAT1 and elo-6/ELOVL3/6, which are related to fatty acid metabolism and mitochondrial β-oxidation. Our data show that disturbed lipid metabolism contributes to neurodegeneration and that nutritional intervention with L. rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial β-oxidation.
Our findings encourage research L. rhamnosus HA-114-derived interventions to modify the progression of neurodegenerative diseases.
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