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Published on: June 2, 2022
Rapamycin and MCC950 modified gut microbiota in experimental autoimmune encephalomyelitis mouse by brain gut axis
Ling Xu1, Cuili Zhang2, Dan He3
1Department of Biotechnology, Dalian Medical University, Dalian 116644, China; Department of Clinical Laboratory, Xinhua Hospital Affiliated to Dalian University, Dalian 116021, China.
Aims:
Multiple sclerosis (MS) whose pathogenesis is still unclear is a chronic progressive disease in the central nervous system. Gut microbiota can directly or indirectly affect the immune system through the brain gut axis to engage in the occurrence and development of the disease.
Materials And Methods:
C57BL/6 mice which were immunized by MOG35-55 to prepare experimental autoimmune encephalomyelitis (EAE) animal models were treated with rapamycin and MCC950 (CP-456773) in combination or separately. After sequencing the 16S rRNA V4 region of gut microbiota, the species, abundance and composition of gut microbiota were analyzed by Alpha diversity, Bata diversity and LEfSe analysis. The pathological changes and the expression of CD4 and CD8 of brain, large intestine and spleen were detected.
Key Findings:
The results showed that rapamycin and MCC950 could alleviate the progression of the disease by inducing autophagy and inhibiting the immune response. The Alpha diversity of EAE model group was no significant difference compering to control group while the number of OTUs was decreased. After the treatment by rapamycin and MCC950, the abundance and composition of gut microbiota was relatively recovered, which was close to that of normal mice.
Significance:
Inhibiting immune cell-mediated inflammation and restoring the composition of gut microbiota may help to alleviate the clinical symptoms of multiple sclerosis. Furthermore, to research the regulatory effect between immune response and gut microbiota may be a new strategy for the prevention and treatment of multiple sclerosis.
Insights
Treatments targeting inflammation and gut microbiota composition show promise in alleviating multiple sclerosis (MS) symptoms. Restoring gut bacteria balance and inhibiting immune responses may offer new therapeutic strategies for MS.
Area of Science:
- Neuroimmunology
- Microbiome Research
- Pharmacology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system disease with unclear pathogenesis.
- The gut microbiota influences the immune system via the brain-gut axis, potentially impacting MS development.
Purpose of the Study:
- To investigate the effects of rapamycin and MCC950 on experimental autoimmune encephalomyelitis (EAE) in mice.
- To analyze the impact of these treatments on gut microbiota composition and immune responses.
Main Methods:
- EAE mouse models were induced and treated with rapamycin and MCC950, alone or in combination.
- Gut microbiota composition was analyzed using 16S rRNA sequencing and diversity metrics (Alpha, Beta, LEfSe).
- Pathological changes and immune cell markers (CD4, CD8) in the brain, spleen, and large intestine were assessed.
Main Results:
- Rapamycin and MCC950 treatments alleviated EAE progression by inducing autophagy and suppressing immune responses.
- While EAE mice showed reduced OTUs compared to controls, treatments partially restored gut microbiota abundance and composition.
- Therapeutic interventions modulated immune cell expression in affected tissues.
Conclusions:
- Inhibiting immune cell-mediated inflammation and restoring gut microbiota balance are potential strategies for managing MS.
- Further research into the immune response-gut microbiota interplay could reveal novel therapeutic targets for MS prevention and treatment.
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