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Human Commensal Prevotella histicola Ameliorates Disease as Effectively as Interferon-Beta in the Experimental Autoimmune Encephalomyelitis
Journal article   Open access   Peer reviewed

Human Commensal Prevotella histicola Ameliorates Disease as Effectively as Interferon-Beta in the Experimental Autoimmune Encephalomyelitis

Shailesh K Shahi, Samantha N Jensen, Alexandra C Murra, Na Tang, Hui Guo, Katherine N Gibson-Corley, Jian Zhang, Nitin J Karandikar, Joseph A Murray and Ashutosh K Mangalam
Frontiers in immunology, Vol.11, pp.578648-578648
2020
DOI: 10.3389/fimmu.2020.578648
PMCID: PMC7759500
PMID: 33362764
url
https://doi.org/10.3389/fimmu.2020.578648View
Published (Version of record) Open Access

Abstract

Gut microbiota has emerged as an important environmental factor in the pathobiology of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Both genetic and environmental factors have been shown to play an important role in MS. Among genetic factors, the human leukocyte antigen (HLA) class II allele such as HLA-DR2, DR3, DR4, DQ6, and DQ8 show the association with the MS. We have previously used transgenic mice expressing MS susceptible HLA class II allele such as HLA-DR2, DR3, DQ6, and DQ8 to validate significance of HLA alleles in MS. Although environmental factors contribute to 2/3 of MS risk, less is known about them. Gut microbiota is emerging as an imporatnt environmental factor in MS pathogenesis. We and others have shown that MS patients have distinct gut microbiota compared to healthy control (HC) with a lower abundance of . Additionally, the abundance of increased in patients receiving disease-modifying therapies (DMTs) such as Copaxone and/or Interferon-beta (IFNβ). We have previously identified a specific strain of ( ), which can suppress experimental autoimmune encephalomyelitis (EAE) disease in HLA-DR3.DQ8 transgenic mice. Since Interferon-β-1b [IFNβ (Betaseron)] is a major DMTs used in MS patients, we hypothesized that treatment with the combination of and IFNβ would have an additive effect on the disease suppression. We observed that treatment with suppressed disease as effectively as IFNβ. Surprisingly, the combination of and IFNβ was not more effective than either treatment alone. alone or in combination with IFNβ increased the frequency and number of CD4 FoxP3 regulatory T cells in the gut-associated lymphoid tissue (GALT). Treatment with alone, IFNβ alone, and in the combination decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4 T cells in the CNS. Additionally, alone or IFNβ alone or the combination treatments decreased CNS pathology, characterized by reduced microglia and astrocytic activation. In conclusion, our study indicates that the human gut commensal can suppress disease as effectively as commonly used MS drug IFNβ and may provide an alternative treatment option for MS patients.
 interferon beta Prevotella histicola experimental autoimmune encephalomyelitis multiple sclerosis human leukocyte antigen transgenic mice

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