Mayo Clinic
Department of Immunology, Division of Gastroenterology and Hepatology

Author Of 1 Presentation

Microbiome Poster Presentation

P0672 - Human commensal Prevotella histicola ameliorates disease in an animal model of multiple sclerosis  as effectively as interferon-beta (ID 1205)

Speakers
Presentation Number
P0672
Presentation Topic
Microbiome

Abstract

Background

We and others have shown that multiple sclerosis (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 disease in Human leukocyte antigen-HLA-DR3.DQ8 transgenic mice, a preclinical animal model of MS. 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.

Objectives

We investigated whether a combination of P. histicola and IFNβ is more effective than either drug alone utilizing an animal model of MS, experimental autoimmune encephalomyelitis (EAE), in HLA-DR3.DQ8 transgenic mice.

Methods

HLA-DR3.DQ8 transgenic mice (8 to 12 weeks old) were immunized subcutaneously in both flanks with proteolipid protein-PLP91–110/CFA/PTX. Mice were divided into four groups treated with IFNβ alone (10,000 IU), live P. histicola alone (108 CFUs), and combination of P. histicola plus IFNβevery alternate day for a total of seven doses. Mice in the control group were orally gavaged with TSB media. All mice were evaluated for EAE scores till the duration of the experiment. CNS pathology, pro-inflammatory cytokines, and anti-inflammatory CD4+Foxp3+ regulatory T cells (Treg) were analyzed after treatments. All experiments were approved by the Institutional Animal Care and Use Committee at the University of Iowa.

Results

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. 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 resulted in milder CNS pathology.

Conclusions

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.

Collapse