Evaluation of Neuroprotective Effect of Gut Microbe in Parkinson's Disease: An In Silico and In Vivo Approach

Study on the Protective Effects of Medicinal Microorganisms on Parkinson’s Disease

Background Introduction

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra region of the brain. The aggregation of α-synuclein is a crucial factor in the pathogenesis of Parkinson’s disease. Studies have shown that gut microbiota can produce neuroprotective effects by interacting with α-synuclein, thereby influencing the progression of Parkinson’s disease. This concept is based on the mechanism of the gut-brain axis, especially the influence of gut microbiota on the nervous system.

Research Source

This paper was written by Kanika Bhardwaj, Neelu Kanwar Rajawat, Nupur Mathur, and Aviral Kaushik from IIS (deemed to be university), University of Rajasthan, and Birla Institute of Scientific Research. The study was submitted on May 16, 2024, and accepted on July 10 of the same year, published in the journal “Neuromolecular Medicine”.

Research Process

Research Design and Techniques

This study aimed to evaluate the protective effects of gut microbiota on α-synuclein aggregation through in silico and in vivo studies. We selected three probiotic strains with potential neuroprotective effects: Lactobacillus casei, Escherichia coli, and Bacillus subtilis, and studied the interaction of their metabolites with α-synuclein.

In Vitro Techniques

First, probiotics with neuroprotective effects were screened through literature review, and relevant papers were searched using biological databases such as NCBI. After selecting the microorganisms and their metabolites, protein-protein interaction analysis was performed using Hex Dock 6.0 software, revealing that methionine synthase produced by Escherichia coli (E. coli) showed the most promising interaction with α-synuclein.

In Vivo Techniques

Following in vitro validation, a rotenone-induced Parkinson’s mouse model was used to further evaluate the neuroprotective effects of E. coli. The experimental design included five groups: control group, rotenone-induced Parkinson’s model group, Levodopa and Carbidopa treatment group, E. coli co-treatment group, and E. coli post-treatment group after rotenone exposure.

Mice in each group underwent behavioral tests (such as grip strength, hanging wire test, and pole test), and biochemical analyses were performed to assess antioxidant capacity and changes in neurotransmitter levels.

Results Analysis

Behavioral Tests

Results showed that mice receiving E. coli treatment performed better in grip strength, hanging wire, and pole tests compared to the Parkinson’s model group exposed to rotenone alone, indicating significant neuroprotective effects of E. coli.

Antioxidant Assessment

Levels of Total Protein, Glutathione Peroxidase, Lipid Peroxidase, and Catalase showed significant improvement in the E. coli treatment group, indicating its positive role in mitigating oxidative stress damage.

Neurotransmitter Analysis

Dopamine and Serotonin levels were significantly increased in the E. coli treatment group, while Monoamine Oxidase A and B activities were significantly reduced, further demonstrating E. coli’s potential to restore neurochemical balance.

Histopathological Evaluation

In the E. coli treatment group, dopaminergic neurons in the substantia nigra were significantly protected, similar to the normal control group, indicating E. coli’s positive role in preventing neuronal degeneration.

Research Significance and Value

Scientific Value

This study reveals the potential protective mechanism of gut microbiota interacting with α-synuclein in Parkinson’s disease, laying the foundation for future exploration of gut microbiota applications in treating Parkinson’s disease.

Clinical Application Value

The discovery of the potential therapeutic effects of gut microbiota, especially E. coli, on Parkinson’s disease may provide new targets and strategies for treating Parkinson’s and other neurodegenerative diseases.

Research Highlights

  1. Innovative Methods: Using comprehensive in vitro and in vivo technical models and interdisciplinary approaches to validate research results.
  2. Important Findings: E. coli demonstrated significant neuroprotective effects, providing new insights for future treatment of Parkinson’s disease.
  3. Precise Validation: Reliability of results proven through detailed behavioral tests and biochemical analyses from multiple angles.

Future Research Directions

Future research should focus on:

  1. Mechanism Exploration: In-depth investigation of the neuroprotective mechanisms of E. coli and its metabolites.
  2. Drug Development: Optimization of dosage and formulation, and conducting clinical trials to evaluate therapeutic efficacy and safety.
  3. Translational Research: Exploring the translational potential of these metabolites as drug candidates.

Conclusion

This study not only provides a new perspective for understanding the complex mechanisms of Parkinson’s disease but also proposes a new approach to utilizing gut microbiota as a potential therapeutic method. Through further research and validation, gut microbiota is expected to play an important role in the treatment of Parkinson’s disease.