Summary: Lacticaseibacillus rhamnosus HA-114, a non-commercial probiotic, reduces neurodegeneration and has neuroprotective effects in laboratory models of ALS.
Source: University of Montreal
Lacticaseibacillus rhamnosus HA-114, a probiotic bacterium, prevents neurodegeneration in the C. elegans worm, an animal model used to study amyotrophic lateral sclerosis (ALS).
This is a new study led by Université de Montréal neuroscience professor Alex Parker of the Canadian CHUM Research Center (CRCHUM) and published in the journal. Communication biology.
He and his team suggest that disruption of lipid metabolism contributes to this cerebral degeneration, showing that the neuroprotection provided by HA-114, a non-commercial probiotic, is unique compared to other strains of the same bacterial family.
“When we add it to the diet of our animal model, we see that it inhibits the progression of motor neuron degeneration,” said Parker, who led the study. The uniqueness of HA-114 resides in its fatty acid content.
Motor neurons, which are nerve cells, allow us to move our bodies as we desire by transmitting signals to the muscles.
People with ALS experience gradual degeneration of their motor neurons. This causes them to lose muscle to complete paralysis with an average life expectancy of 3 to 5 years at the time of diagnosis.
About 3,000 people in Canada have ALS.
“Recent studies have shown that disruption of the gut microbiota may be involved in the onset and progression of many incurable neurodegenerative diseases, including ALS,” Parker explained.
Identification of neuroprotective bacterial strains may provide the basis for new treatments.
The lead author of this scientific project, Audrey Labarre, is a postdoctoral fellow working hard to research ALS with a focus on motor neuron degeneration in C. elegans worms.
Measuring just one millimeter in length and sharing 60% of their genetic makeup with humans, these nematodes have been genetically modified with ALS-related genes for CRCHUM research purposes.
To study the neuroprotective effects of a probiotic-based dietary supplement in this animal model, Labare tested a total of 13 different bacterial strains and three species combinations.
HA-114 out of the box. The action of the probiotic helped reduce motor deficits in models of ALS and Huntington’s disease, another neurodegenerative disease.
Two genes at play
Based on genetic studies, genomic profiling, behavioral analysis and microscopic imaging, the scientific team identified two genes that play a key role in this neuroprotective mechanism: acdh-1 and acs-20.
In collaboration with CRCHUM researcher Martin Terewalt and researcher Mathieu Ruiz at the Montreal Heart Institute Research Center, they were able to carry out this meticulous work.
In humans, both genes in their equivalent forms are involved in lipid metabolism and beta oxidation, the process by which fatty acids are broken down into energy in the mitochondria, the true cellular powerhouses.
“We believe that the fatty acids provided by HA-114 enter the mitochondria in an independent and non-traditional way,” said Parker, “and in doing so, they restore the balance of impaired energy metabolism in ALS and reduce neurodegeneration.”
The research team is now conducting similar studies on a more complex animal model than the C. elegans worm: the mouse.
They then clinically confirm that HA-114 can be a therapeutic adjunct to current ALS treatments. The advantage, they say, is that probiotics have fewer side effects than drugs.
To this end, a Canada-wide clinical study will be conducted in 100 cases beginning in the spring of 2023, led by Dr. Genevieve Mate, Director of the CRCHUM Headquarters and ALS Clinic.
So ALS research news
Preliminary study: Open Access.
“Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 prevent age-related neurodegeneration.” by Audrey Labarre et al. Communication biology
Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 prevent age-related neurodegeneration.
The human microbiota is believed to influence health. Microbiome dysbiosis may be linked to neurological conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. We report the ability of probiotic bacterial strains to halt the neurodegenerative phenotype.
We show that. Lacticaseibacillus rhamnosus HA-114 is a neuroprotective agent C. elegans Models of amyotrophic lateral sclerosis and Huntington’s disease. Our results show that neuroprotection from L. rhamnosus HA-114 is different. L. rhamnosus It is formed and exists in the fatty acid content.
Neuroprotection by L. rhamnosus It requires HA-114 acdh-1/ACADSfor, Cat-1/ACAT1 And elo-6/ELOVL3/6, are related to fatty acid metabolism and mitochondrial β-oxidation. Our data suggest that impaired lipid metabolism contributes to neurodegeneration and nutritional interventions. L. rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial β-oxidation.
Our findings encourage exploration L. rhamnosus HA-114-derived interventions to improve the progression of neurodegenerative diseases.