A rationally designed microbial consortium modulates neurodegeneration in a Drosophila melanogaster model of Parkinson's disease.

2025-09-24
NPJ biofilms and microbiomes 11(1)

PubMed: 40993130
DOI: 10.1038/s41522-025-00797-5

Study Design

Population: Drosophila melanogaster model of neurodegeneration of Parkinson's Disease (PD)
Methods: Using genome-scale metabolic modeling, we designed and tested a synthetic microbial consortium with predicted capacity to produce GABA and other neurometabolites; the consortium (Levilactobacillus brevis, Lacticaseibacillus paracasei, Bacteroides thetaiotaomicron) produced GABA in bioreactors

Animal Study

The gut-brain axis enables communication between the central nervous system and the gut, with certain microbial metabolites influencing neurodegeneration. Using genome-scale metabolic modeling, we designed and tested a synthetic microbial consortium with predicted capacity to produce GABA and other neurometabolites in a Drosophila melanogaster model of neurodegeneration of Parkinson's Disease (PD). The consortium (Levilactobacillus brevis, Lacticaseibacillus paracasei, Bacteroides thetaiotaomicron) produced GABA in bioreactors. Female PD flies receiving the consortium exhibited protection from locomotor impairment at 10 and 25 days upon consortium administration. Head metabolomics revealed partial restoration of PD-associated alterations in energy balance, amino acid and neurotransmitter metabolism, and disease-related biomarkers. Early administration increased microbiome diversity and Lactobacillus abundance. These findings suggest that rationally designed microbial consortia targeting neurometabolite production can modulate brain physiology and confer neuroprotection, supporting their potential for microbiome-based interventions in neurodegenerative disease.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus brevis Lbr-35	—	Increased Microbial Diversity	Beneficial	Small	View source Early administration increased microbiome diversity and Lactobacillus abundance.
Lactobacillus brevis Lbr-35	—	Reduced Locomotor Impairment	Beneficial	Moderate	View source Female PD flies receiving the consortium exhibited protection from locomotor impairment at 10 and 25 days upon consortium administration.
Lactobacillus brevis Lbr-35	—	Restored Neurodegeneration-Associated Metabolic Alterations	Beneficial	Moderate	View source Head metabolomics revealed partial restoration of PD-associated alterations in energy balance, amino acid and neurotransmitter metabolism, and disease-related biomarkers.