Gut microbiota-associated taurine metabolism dysregulation in a mouse model of Parkinson’s disease Original paper

What was studied?

This study investigated the interplay between gut microbiota composition, serum metabolite profiles, and the pathogenesis of Parkinson’s disease (PD) in a mouse model. Specifically, the researchers aimed to elucidate how dysbiosis of gut microbiota and associated metabolic disturbances, particularly in taurine metabolism, contribute to PD development. The study utilized 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like pathology in mice. Using 16S rRNA gene sequencing and untargeted metabolomics via ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC-QE/MS), the team profiled the gut microbiome and serum metabolome. They further investigated the functional links between specific microbial genera, taurine-related metabolites, and PD pathology, and tested the effects of taurine supplementation on disease progression. The focus keyphrase, “taurine-based microbiome-metabolism axis in Parkinson’s disease,” is central to the study’s objective of mapping microbiome signatures relevant to PD.

Who was studied?

The research was conducted on male C57BL/6 mice aged 8–10 weeks, weighing 25–30 grams. These mice were housed under specific pathogen-free conditions. The PD model was established by intraperitoneal injection of MPTP at 30 mg/kg for five consecutive days. Control mice received saline injections. For the taurine supplementation arm, mice received 150 mg/kg taurine intraperitoneally for four weeks, with PD induction occurring after two weeks of taurine treatment. Behavioral, pathological, and biochemical analyses were performed on these animals, with sample sizes for various assays (e.g., behavioral tests, immunohistochemistry, metabolomics, and microbiota analyses) ranging from 3 to 10 per group.

Most important findings

The study demonstrated that MPTP-induced PD mice exhibited classic motor deficits, dopaminergic neuron loss, neuroinflammation, and both central and colonic barrier dysfunction. Microbiome analysis revealed a significant reduction in bacterial diversity and richness in PD mice, with increased abundances of Aerococcus, Staphylococcus, and Ruminococcaceae, and decreased abundances of Lactobacillus, Lachnospiraceae, and Adlercreutzia compared to controls. Metabolomic profiling highlighted a marked downregulation of metabolites involved in taurine and hypotaurine metabolism in PD mice, notably taurine itself, 3-sulfinoalanine, and taurocholic acid.

Correlation analyses identified strong associations between the levels of Lactobacillus, Adlercreutzia, taurine-related metabolites, and key PD pathological features, including motor impairment and neuroinflammation. Functional prediction indicated upregulated microbial pathways for taurine degradation (e.g., increased taurine ABC transporter, taurine dioxygenase, and alkanesulfonate dioxygenase) in PD mice, suggesting enhanced microbial catabolism of taurine as a driver of its systemic depletion. Most compellingly, taurine supplementation alleviated motor deficits, rescued dopaminergic neuron loss, and reduced microglial activation in MPTP-treated mice, underscoring the neuroprotective potential of restoring taurine metabolism.

Key implications

This study provides compelling evidence for a taurine-based microbiome-metabolism axis in Parkinson’s disease. The findings suggest that dysbiosis—specifically, the loss of beneficial genera such as Lactobacillus and Adlercreutzia and the enrichment of potentially pathogenic taxa—leads to increased microbial taurine degradation, reduced systemic taurine, and exacerbation of PD pathology. The close association between specific microbiome signatures and taurine metabolism highlights their potential as biomarkers for PD progression and as targets for therapeutic intervention. Taurine supplementation—or strategies to restore beneficial gut microbes—may represent promising adjunctive therapies to ameliorate both neurological and gastrointestinal aspects of PD, bridging microbial ecology with clinical management.

Citation

Cui C, Song H, Han Y, Yu H, Li H, Yang Y, Zhang B. Gut microbiota-associated taurine metabolism dysregulation in a mouse model of Parkinson’s disease. mSphere. 2023;8(6):e00431-23. doi:10.1128/msphere.00431-23