Gut microbiome and MS pathogenesis


REPORT FROM THE ACTRIMS-ECTRIMS – BOSTON, MA, SEPTEMBER 10-13, 2014 – Several lines of evidence indicate that the gut microbiome plays a role in the pathogenesis of MS. It has been suggested that environmental risk factors, such as diet, vitamin D insufficiency, obesity and smoking, may contribute to alterations in the GI flora that may predispose to autoimmune dysregulation (Joscelyn & Kasper. Mult Scler 2014; epublished July 28, 2014).

Gut flora, such as Bacteroides fragilis, produce short-chain fatty acids which have been shown in animal models to have anti-inflammatory effects on peripheral immune cells and which are involved in the proliferation of regulatory T cells (Tregs) (Smith et al. Science 2013;341:569-573; Maslowski et al. Nature 2009;461:1282-1286; Furusawa et al. Nature 2013;504:446-450).

One area of interest is polysaccharide A (PSA) produced by B. fragilis, which has been shown to activate afferent neurons in the enteric nervous system (Mao et al. Nat Commun 2013; 4:1465.). Oral administration of PSA was shown to have both prophylactic and therapeutic effects in EAE mice by inducing the conversion of naïve CD4+ T cells to Tregs that produced IL-10 (Ochoa-Reparaz et al. Mucosal Immunol 2010;3:487-495).

This work was updated at ACTRIMS-ECTRIMS with new data (Kasper et al. ECTRIMS 2014; abstract P611). An in vitro study of human peripheral blood mononuclear cells (PBMC) exposed to PSA showed a dose-dependent increase in Tregs producing IL-10 and a corresponding decrease in TNF-alpha. This is the first study to show that a gut bacterial product can contribute to a regulatory T cell response in humans.

A separate study analysed stool samples from 20 pediatric MS cases (mean duration 11 months, median EDSS 2.0) and 16 controls to determine if there were differences in the gut microbiome (Tremlett et al. ECTRIMS 2014; abstract P615). The preliminary results showed that MS patients had significantly more Proteobacteria (Shigella, Escherichia) and Firmicutes (Clostridium), and comparatively less Firmicutes (Eubacterium rectale) and Actinobacteria (Corynebacterium) compared to controls. The MS cases were more commonly exposed to antibiotics (2 vs. 1 subject), corticosteroids (8 vs. 2) and immunomodulatory/immunosuppressant drugs (10 vs. 2), which may have contributed to alterations in the gut microflora and an increased burden of selective pathogens.

The MS Microbiome Consortium is currently analysing blood and stool samples from MS patients in New York (Mount Sinai) and San Francisco (UCSF) to determine how the gut microbiome is affected by diet and immunomodulatory therapies, and will examine the relationship between gut flora, MS phenotype and MS disease activity (Baranzini et al. ECTRIMS 2014; abstract P618).

Guest Reviewer: Dr. Daniel Selchen, St. Michael’s Hospital, Toronto, Ontario.

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