Researchers have investigated the neuroprotective capacity of probiotics. The study, published in Communications Biology, identified a probiotic bacterium that protects against neurodegeneration in a worm model of amyotrophic lateral sclerosis (ALS).
Motor Neurons
Motor neurons are a part of the peripheral nervous system. They transmit impulses to muscles which trigger muscle contractions and movement. ALS is the most prevalent motor neuron disease. It is characterised by muscle weakness and stiffness, which progresses to paralysis due to gradual degeneration of lower and upper motor neurons. Recent studies have highlighted the importance of the human microbiota in health and have linked microbial dysbiosis to neurological diseases.
Researchers at Canada’s CHUM Research Centre (CRCHUM) investigated the neuroprotective capacity of a non-commercial probiotic organism, Lacticaseibacillus rhamnosuas.
Alex Parker, study lead at the CRCHUM and Associate Professor of Neuroscience at the University of Montreal said, “Recent research has shown that the disruption of the gut microbiota is likely involved in the onset and progression of many incurable neurodegenerative diseases, including ALS.”
Experimental approach
C. elegans, which is a nematode, was used as the animal model to study ALS. C. elegans ALS strains were created by genetically modifying the nematodes with ALS-associated genes.
The neuroprotective properties of 13 different strains of L. rhamnosuas and 3 strain combinations were investigated. The L. rhamnosuas HA-114 strain was the most effective probiotic at reducing motor disorders in both ALS and Huntington’s disease models (another neurodegenerative disorder).
Mitochondria is the powerhouse of the cell
So, what connects this bacterium to neuroprotective mechanisms? Mitochondria is the answer! The researchers suggest that disrupted metabolism of lipids contributes to neuronal degeneration and the subsequent pathology of ALS.
The researchers used genomic profiling, behavioural analysis and microscopy to identify 2 genes that are important in neuroprotection: acdh-1 and acs-20. The genes are involved in the breakdown of lipids and beta-oxidation, which is where fatty acids are broken down in the mitochondria to release energy. L. rhamnosuas HA-114 supplies fatty acids that enter the mitochondria. This restores the disrupted lipid metabolism that underpins neurodegeneration in ALS (figure 1).
Associate Professor Parker said, “When we add [L. rhamnosuas HA-114] to the diet of our animal model, we notice that it suppresses the progression of motor neuron degeneration. The particularity of HA-114 resides in its fatty acid content.”
From worms to mice
The C. elegans model used in this study provided insight into the neuroprotective mechanism of L. rhamnosuas HA-114. Researchers hope to conduct similar studies on mouse models, which are more complex and more like humans. The bacterium could form the basis for new probiotic-based therapies in neurodegenerative disease.
