The human microbiota is believed to influence health. Microbiome dysbiosis may be linked to neurological conditions like Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. We report the ability of a probiotic bacterial strain in halting neurodegeneration phenotypes. We show that Lacticaseibacillus rhamnosus HA-114 is neuroprotective in C. elegans models of amyotrophic lateral sclerosis and Huntington’s disease. 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 associated with fatty acid metabolism and mitochondrial β-oxidation. 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. Our findings encourage the exploration of L. rhamnosus HA-114 derived interventions to modify the progression of neurodegenerative diseases.

Niemann–Pick disease type C (NPC) is a treatable autosomal recessive neurodegenerative condition which leads to a variety of progressive manifestations. Despite most cases being diagnosed at a young age, disease prevalence may be underestimated, especially in adults, and interpretation of NPC1 and NPC2 variants can be difficult. This study aims to identify potential pathogenic variants in a large cohort of healthy individuals and classify their risk of pathogenicity to assist with future interpretation of variants. The CARTaGENE (CaG) cohort was used to identify possible variants of NPC1 and NPC2. Nine-hundred and eleven RNA samples and 198 exome sequencing were screened for genetic variants through a bio-informatic pipeline performing alignment and variant calling. The identified variants were analyzed using annotations for allelic frequency, pathogenicity and conservation scores. The ACMG guidelines were used to classify the variants. These were then compared to existing databases and previous studies of NPC prevalence, including the Tübingen NPC database. Thirty-two distinct variants were identified after running the samples in the RNA-sequencing pipeline, two of which were classified as pathogenic and 21 of which were not published previously. Furthermore, 46 variants were both identified in our population and with the Tübingen database, the majority of which were of uncertain significance. Ten additional variants were found in our exome-sequencing sample. This study of a sample from a population living in Quebec demonstrates a variety of rare variants, some of which were already described in the literature as well as some novel variants. Classifying these variants is arduous given the scarcity of available literature, even so in a population of healthy individuals. Yet using this data, we were able to identify two pathogenic variants within our population and several new variants not previously identified.

Niemann–Pick type C (NP-C) disease is an autosomal recessive disease caused by variants in the NPC1 or NPC2 genes. It has a large range of symptoms depending on age of onset, thus making it difficult to diagnose. In adults, symptoms appear mainly in the form of psychiatric problems. The prevalence varies from 0.35 to 2.2 per 100,000 births depending on the country. The aim of this study is to calculate the estimated prevalence of NP-C in Quebec to determine if it is underdiagnosed in this population. The CARTaGENE database is a unique database that regroups individuals between 40 and 69 years old from metropolitan regions of Quebec. RNA-sequencing data was available for 911 individuals and exome sequencing for 198 individuals. We used a bioinformatic pipeline on those individuals to extract the variants in the NPC1/2 genes. The prevalence in Quebec was estimated assuming Hardy–Weinberg Equilibrium. Two pathogenic variants were used. The variant p.Pro543Leu was found in three heterozygous individuals that share a common haplotype, which suggests a founder French-Canadian pathogenic variant. The variant p.Ile1061Thr was found in two heterozygous individuals. Both variants have previously been reported and are usually associated with infantile onset. The estimated prevalence calculated using those two variants is 0.61:100,000 births. This study represents the first estimate of NP-C in Quebec. The estimated prevalence for NP-C is likely underestimated due to misdiagnosis or missed cases. It is therefore important to diagnose all NP-C patients to initiate early treatment.

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