Probiotic Lacticaseibacillus rhamnosus HA-114 suppresses age-dependent neurodegeneration via mitochondrial beta-oxidation

Abstract

The human microbiota is believed to influence health. Microbiome dysbiosis may be linked to neurological conditions like Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). We report the ability of a probiotic bacterial strain in reversing neurodegeneration phenotypes. We show that Lacticaseibacillus rhamnosus HA-114 is neuroprotective in C. elegans models of ALS and HD. Our results show that neuroprotection from L. rhamnosus HA-114 is unique from other L. rhamnosus strains, and resides in its fatty acid content. Neuroprotection by L. rhamnosus HA-114 requires acdh-1/ACADSB, kat-1/ACAT1 and elo-6/ELOVL3/6, which are key fatty acid metabolism and mitochondrial β-oxidation genes. Moreover, L. rhamnosus HA-114 delayed disease onset and suppressed motor neuron degeneration in an aggressive mouse model of ALS. 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. L. rhamnosus HA-114 is suitable for human consumption opening the possibility of modifying disease progression by dietary intervention.

Simple models to understand complex disease: 10 years of progress from Caenorhabditis elegans models of amyotrophic lateral sclerosis and frontotemporal lobar degeneration

“…For example, fatty acids derived from the bacteria Lacticaseibacillus rhamnosus HA-114 reduce aberrant lipid accumulation, motor deficits, and neurodegeneration in C. elegans expressing mutant FUS(S57Δ) or TDP-43(A315T) in GABAergic motor neurons. This rescue acts through genes involved in lipid homeostasis and mitochondrial β-oxidation, suggesting both pathways are critical to ALS (Labarre et al, 2022). C. elegans models of FUS have identified mechanisms contributing to FUS-driven ALS including FUS mislocalization, autophagic disruption, and protein synthesis dependent synaptic dysfunction.…”

Novel Insights into the Role of Probiotics in Respiratory Infections, Allergies, Cancer, and Neurological Abnormalities

“…During the pathogenesis of AD, there are numerous involved factors in the disease progression, and the principal hallmarks are commonly linked with the overproduction of ROS that induces neuroinflammation and consequently cellular death, the progression of A-β plaques, peptides and oligomers, microglial activation, neurofibrillary tangles, mitochondrial damage and vascular abnormalities [100,104]. Afflicted lipid metabolism could trigger neurodegenerative processes, and reversely Labarre et al have shown that dietary treatment with L. rhamnosus HA-114 restored lipid homeostasis, including energy balance via mitochondrial b-oxidation [105]. According to previously documented studies, probiotics have shown impressive ability to decelerate AD advancement due to clinically proved anti-inflammatory and antioxidant effects, including their ability to normalize cognitive deterioration that appreciably highlights their therapeutic applicability and effectiveness [106][107][108][109].…”