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

Autor:	Shahi SK; Department of Pathology, University of Iowa, Iowa City, IA, United States., Jensen SN; Department of Pathology, University of Iowa, Iowa City, IA, United States.; Graduate Program in Immunology, University of Iowa, Iowa City, IA, United States., Murra AC; Department of Pathology, University of Iowa, Iowa City, IA, United States., Tang N; Department of Pathology, University of Iowa, Iowa City, IA, United States., Guo H; Department of Pathology, University of Iowa, Iowa City, IA, United States., Gibson-Corley KN; Department of Pathology, University of Iowa, Iowa City, IA, United States., Zhang J; Department of Pathology, University of Iowa, Iowa City, IA, United States., Karandikar NJ; Department of Pathology, University of Iowa, Iowa City, IA, United States.; Graduate Program in Immunology, University of Iowa, Iowa City, IA, United States.; Graduate Program in Molecular Medicine, University of Iowa, Iowa City, IA, United States., Murray JA; Department of Immunology, Mayo Clinic, Rochester, MN, United States.; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States., Mangalam AK; Department of Pathology, University of Iowa, Iowa City, IA, United States.; Graduate Program in Immunology, University of Iowa, Iowa City, IA, United States.; Graduate Program in Molecular Medicine, University of Iowa, Iowa City, IA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Dec 11; Vol. 11, pp. 578648. Date of Electronic Publication: 2020 Dec 11 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.578648
Abstrakt:	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 Prevotella . Additionally, the abundance of Prevotella increased in patients receiving disease-modifying therapies (DMTs) such as Copaxone and/or Interferon-beta (IFNβ). We have previously identified a specific strain of Prevotella ( Prevotella histicola ), 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 P. histicola and IFNβ would have an additive effect on the disease suppression. We observed that treatment with P. histicola suppressed disease as effectively as IFNβ. Surprisingly, the combination of P. histicola and IFNβ was not more effective than either treatment alone. P. histicola 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 P. histicola alone, IFNβ alone, and in the combination decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4 + T cells in the CNS. Additionally, P. histicola 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 P. histicola can suppress disease as effectively as commonly used MS drug IFNβ and may provide an alternative treatment option for MS patients. Competing Interests: AKM and JM are inventors of a technology claiming the use of Prevotella histicola for the treatment of autoimmune diseases. The patent for the technology is owned by Mayo Clinic, who has given exclusive license to Evelo Biosciences. AKM and JM received royalties from Mayo Clinic (paid by Evelo Biosciences). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2020 Shahi, Jensen, Murra, Tang, Guo, Gibson-Corley, Zhang, Karandikar, Murray and Mangalam.)
Databáze:	MEDLINE
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