Gut Microbiome-Dependent Metabolic Remodeling and Its Impact on α-Synuclein Phenotype in Caenorhabditis elegans
- 1Institute of Parasitology, McGill University, Sainte Anne de Bellevue, QC H9X 3V9, Canada
- 2Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada
Abstract
Background: Parkinson’s disease (PD), which affects more than six million people, is marked by the aggregation of α-synuclein and the progressive loss of dopaminergic neurons. Most cases are sporadic, and the factors that trigger them are still poorly defined. One proposed contributor is the gut microbiome, which may influence disease through its effects on host metabolism. Here, we used Caenorhabditis elegans to examine how individual gut bacteria shape host metabolism and PD-related phenotypes. Methods: Intestinal colonization was first quantified in wild-type worms and in mutants lacking TOL-1, the only Toll-like receptor homolog in this nematode, and the worm metabolome was then profiled by untargeted LC-MS/MS. Results: Loss of TOL-1 altered the bacterial load in the gut and shortened lifespan only on the pathogen Salmonella enterica. Metabolomic profiling showed that colonization reshaped host metabolism in a TOL-1-dependent way, with retinol metabolism among the most affected pathways; this effect was strongest in worms fed Rhodococcus erythropolis MYb53, a bacterium native to the worm microbiome. In an α-synuclein-expressing strain, R. erythropolis postponed the appearance of aggregates and maintained motility in older animals, although aggregate numbers eventually increased late in life. Conclusions: Motor decline was therefore uncoupled from aggregate load, indicating that this native bacterium protects the motor phenotype rather than preventing aggregation itself. Overall, our results support C. elegans as a tractable system for dissecting how the gut microbiome contributes to PD.
Related
- Single-shot light-field microscopy captures delivery-dependent dye and autofluorescence patterns in Caenorhabditis elegans
- Faecal microbiota transplant revisited - potential metabolic outcomes of regional microbiome mismatches.
- Gut microbiome composition and oxalate-related metabolic functions in staghorn calcium oxalate stone formers: a shotgun metagenomic analysis
- Vegans have distinct profiles of their gut microbiome and multi-compartment metabolome that align with markers of metabolic health
- Metabolic Remodeling in Peritoneal Dialysis-Associated Peritoneal Fibrosis: Mechanisms, Candidate Metabolic Signatures, and Therapeutic Perspectives
BibTeX
@article{nouar2026microbiomedependent,
title = {{Gut Microbiome-Dependent Metabolic Remodeling and Its Impact on α-Synuclein Phenotype in Caenorhabditis elegans}},
author = {Alyssa Nouar and Charles Viau and Suhisna Dutta and Zhiqiang Pang and Jianguo Xia},
journal = {Metabolites},
year = {2026},
month = nov,
doi = {10.3390/metabo16110851},
url = {https://www.mdpi.com/2218-1989/16/11/851},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gut Microbiome-Dependent Metabolic Remodeling and Its Impact on α-Synuclein Phenotype in Caenorhabditis elegans
AU - Alyssa Nouar
AU - Charles Viau
AU - Suhisna Dutta
AU - Zhiqiang Pang
AU - Jianguo Xia
PY - 2026
DA - 2026/11/04
JO - Metabolites
DO - 10.3390/metabo16110851
UR - https://www.mdpi.com/2218-1989/16/11/851
AB - Background: Parkinson’s disease (PD), which affects more than six million people, is marked by the aggregation of α-synuclein and the progressive loss of dopaminergic neurons. Most cases are sporadic, and the factors that trigger them are still poorly defined. One proposed contributor is the gut microbiome, which may influence disease through its effects on host metabolism. Here, we used Caenorhabditis elegans to examine how individual gut bacteria shape host metabolism and PD-related phenotypes. Methods: Intestinal colonization was first quantified in wild-type worms and in mutants lacking TOL-1, the only Toll-like receptor homolog in this nematode, and the worm metabolome was then profiled by untargeted LC-MS/MS. Results: Loss of TOL-1 altered the bacterial load in the gut and shortened lifespan only on the pathogen Salmonella enterica. Metabolomic profiling showed that colonization reshaped host metabolism in a TOL-1-dependent way, with retinol metabolism among the most affected pathways; this effect was strongest in worms fed Rhodococcus erythropolis MYb53, a bacterium native to the worm microbiome. In an α-synuclein-expressing strain, R. erythropolis postponed the appearance of aggregates and maintained motility in older animals, although aggregate numbers eventually increased late in life. Conclusions: Motor decline was therefore uncoupled from aggregate load, indicating that this native bacterium protects the motor phenotype rather than preventing aggregation itself. Overall, our results support C. elegans as a tractable system for dissecting how the gut microbiome contributes to PD.
SN - 2218-1989
ER -