Probiotic protects against ALS in worm model

CRCHUM scientists discover that a bacterium called Lacticaseibacillus rhamnosus HA-114 prevents neurodegeneration of the C.elegans worm used to study amyotrophic lateral sclerosis.

A probiotic bacterium called Lacticasibacillus rhamnosus HA-114 prevents neurodegeneration in the C.elegans worm, an animal model used to study amyotrophic lateral sclerosis (ALS).

It is 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 notice that it suppresses the progression of motor neuron degeneration,” said Parker, the study’s lead author. “The particularity of HA-114 lies in its fatty acid content.”

By allowing signals to be transmitted to muscles to contract, motoneurons, which are nerve cells, allow us to move our bodies at will.

People with ALS experience progressive deterioration of their motor neurons. This causes them to lose their muscle capacity, up to total paralysis, with an average life expectancy of only 3 to 5 years after diagnosis.

Nearly 3,000 people in Canada have ALS.

“Recent research has shown that disruption of the gut microbiota is likely implicated in the onset and progression of many incurable neurodegenerative diseases, including ALS,” Parker explained.

The identification of neuroprotective bacterial strains could form the basis of new therapies.

A matter of diet

At the heart of this scientific project is Audrey Labarrethe study’s first author, a postdoctoral fellow working hard to advance ALS research by focusing on motor neuron degeneration in C.elegans toward.

Measuring only one millimeter in length and sharing 60% of their genetic make-up with humans, these nematodes have been genetically modified with genes associated with ALS for the needs of CRCHUM research.

To study the neuroprotective effects of a probiotic-based food supplement on this animal model, Labarre tested a total of 13 different bacterial strains and three strain combinations.

HA-114 stood out from the pack. The action of the probiotic has reduced motor disorders in models with ALS and also Huntington’s disease, another neurodegenerative disease.

Two genes at play

Using 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 accomplish this meticulous work thanks to collaborations with Martine Tetreaultresearcher at the CRCHUM, and Matthieu Ruiz, researcher at the Montreal Heart Institute Research Center.

Existing in equivalent forms in humans, the two genes are involved in lipid metabolism and beta-oxidation, a process by which fatty acids are broken down into energy in the mitochondria, true cellular energy centres.

“We believe that the fatty acids provided by HA-114 enter the mitochondria by an independent and non-traditional route,” Parker said. In doing so, they restore the balance of the altered energy metabolism in ALS and lead 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 complement to current ALS treatments. The advantage is that probiotics, unlike drugs, produce few side effects, they say.

To this end, a pan-Canadian clinical study headquartered at the CRCHUM and led by Dr. Genevieve Matte will be conducted with 100 subjects, starting in the spring of 2023.

Reference: Labarre A, Guitard E, Tossing G, et al. Probiotic-derived fatty acids Lacticasibacillus rhamnosus HA-114 suppresses age-dependent neurodegeneration. Common Biol. 2022;5(1):1-19. do I: 10.1038/s42003-022-04295-8

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