Lallemand’s HA-114 probiotic strain shows neuroprotective promise

"Our data suggest that disrupted lipid metabolism contributes to neurodegeneration and that dietary intervention with L. rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial β-oxidation,” ​the researchers wrote.

The study, published in the journal Communications Biology​ was funded by ALS Canada, Brain Canada, the Natural Sciences and Engineering Research Council of Canada and the Weston Family Foundation.  

Dysbiosis and neurodegeneration​

Recent research has shown that the disruption of the gut microbiota, known as dysbiosis, may be linked through the gut-brain axis to the onset and progression of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), multiple sclerosis, Alzheimer’s and Parkinson’s disease.

“We believe there is a general imbalance of lipids in the disease state, and this compromises energy production which in turn contributes to neurodegeneration during aging” ​explained Alex Parker, Ph.D., a professor in the department of neuroscience at the University of Montreal and lead author on the study.

“Several microbiome studies have identified putative pathogenic bacterial strains; however, it has been difficult to identify probiotic bacterial strains that could protect against neurological conditions.”​

The research team first identified HA-114 while working with a collection of probiotic strains from Lallemand Health Sciences for a separate project focused on weight loss applications before deciding to test the strains in the lab’s models for ALS.

Study details​

The study was carried out in a model of C. elegans​ invertebrates genetically modified with ALS-associated genes. A combination of genetics, genome profiling, behavioral analysis and microscopy was used to screen for the effects of 13 individual strains and three combinations of probiotic bacteria, all provided by Lallemand. HA-114 was the only one to show significant effects on motor disorders and neurodegeneration. 

As potential mechanism, Dr. Parker pointed to the ability of “HA-114 to provide specific fatty acid molecules that can bypass the block in lipid metabolism, thus providing the neurons energy to fight neurodegeneration.”​

The study identified acdh-1 and kat-1, genes implicated in fatty acid metabolism and β-oxidation, as the core components of this neuroprotective mechanism. It also found that the strain’s beneficial effect could be extended to other genetic models of age-dependent neurodegeneration, including Huntington’s disease.

The next set of experiments is already underway in mouse models with encouraging preliminary data, Parker said, and a clinical trial for ALS is slated to start this year. The research continues to be supported by a three-year $1.6 million grant from the Weston Family Foundation as part its Brain Health: 2021 – Lifestyle Approaches and Microbiome Contributions program​. 

Source: Communications Biology 5, 1340 (2022)
doi: 10.1038/s42003-022-04295-8​
“Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-dependent neurodegeneration”​
Authors: Audrey Labarre et al.