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Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice
Kerstin Berer1, Lisa Ann Gerdes2, Egle Cekanaviciute3
1Hertie Senior Professor Group, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
Abstract:
There is emerging evidence that the commensal microbiota has a role in the pathogenesis of multiple sclerosis (MS), a putative autoimmune disease of the CNS. Here, we compared the gut microbial composition of 34 monozygotic twin pairs discordant for MS. While there were no major differences in the overall microbial profiles, we found a significant increase in some taxa such as Akkermansia in untreated MS twins. Furthermore, most notably, when transplanted to a transgenic mouse model of spontaneous brain autoimmunity, MS twin-derived microbiota induced a significantly higher incidence of autoimmunity than the healthy twin-derived microbiota. The microbial profiles of the colonized mice showed a high intraindividual and remarkable temporal stability with several differences, including Sutterella, an organism shown to induce a protective immunoregulatory profile in vitro. Immune cells from mouse recipients of MS-twin samples produced less IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10 may have a regulatory role in spontaneous CNS autoimmunity, as neutralization of the cytokine in mice colonized with healthy-twin fecal samples increased disease incidence. These findings provide evidence that MS-derived microbiota contain factors that precipitate an MS-like autoimmune disease in a transgenic mouse model. They hence encourage the detailed search for protective and pathogenic microbial components in human MS.
Insights
The gut microbiota of individuals with multiple sclerosis (MS) can trigger autoimmune disease in mice. This suggests specific gut microbes may contribute to MS pathogenesis, warranting further investigation into protective and harmful microbial factors.
Area of Science:
- Neuroimmunology
- Microbiome Research
- Autoimmune Diseases
Background:
- The gut microbiota is increasingly implicated in the pathogenesis of central nervous system (CNS) autoimmune diseases like multiple sclerosis (MS).
- Understanding the specific microbial contributions to MS is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of gut microbial composition in multiple sclerosis (MS) pathogenesis.
- To determine if microbiota from MS patients can induce autoimmunity in a susceptible host.
Main Methods:
- Comparison of gut microbial composition in monozygotic twin pairs discordant for MS.
- Fecal microbiota transplantation from MS and healthy twins into a transgenic mouse model of spontaneous brain autoimmunity.
- Analysis of immune cell cytokine production (IL-10) and disease incidence in recipient mice.
Main Results:
- Increased abundance of certain taxa, like *Akkermansia*, observed in untreated MS twins.
- Microbiota from MS twins induced a higher incidence of autoimmunity compared to microbiota from healthy twins when transplanted into mice.
- Reduced IL-10 production by immune cells in mice receiving MS-twin microbiota, suggesting a link between IL-10 and disease regulation.
Conclusions:
- Gut microbiota from individuals with MS contains factors that can precipitate an MS-like autoimmune disease in a mouse model.
- These findings highlight the potential of specific microbial components in driving MS pathogenesis.
- Further research is encouraged to identify protective and pathogenic microbial factors in human MS.
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