A number of recent studies have suggested that alterations in the gut microbiome (dysbiosis) may contribute to the onset and/or worsening of multiple sclerosis. Two new papers, scheduled for publication this week, report that certain bacterial strains promote neurodegeneration in the EAE mouse model (Cekanaviciute and colleagues. PNAS 2017; in press).
The first study analysed the microbiome of MS patients and healthy controls and identified two bacterial strains that were more common in MS patients; other strains were found to be more common in healthy subjects. The MS-related strains were subsequently found to induce a pro-inflammatory response when cultured with immune cells in vitro. The strains found more abundantly in healthy controls induced an immune-regulatory response. The same effects were seen when bacterial extracts were administered to mice.
In a second experiment, fecal transplantation from MS patients to EAE mice resulted in more severe neurodegeneration. Fecal transplantation, rather than transfer of specific bacterial species, was used to more closely reflect the complex interactions of the gut microbiota. Worsening neurodegeneration was attributed to the loss of immune-regulatory mechanisms in transplanted mice.
Previous studies have identified alterations in microbiome species in MS patients compared to healthy controls (Jangi et al. Nat Commun 2016;7:12015; Miyake et al. PLoS One 2015;10:e0137429). These alterations were associated with variations in the expression of genes involving interferon and NF-kappaB signalling in T cells and monocytes. Also noteworthy is that vitamin D, as well as some disease-modifying therapies used in MS (e.g. glatiramer acetate, dimethyl fumarate), have been shown to alter gut microbiota (Cantarel et al. J Investig Med 2015;63:729-734. Katz Sand et al. AAN 2017; abstract P6.379).
The University of British Columbia group has reported that alterations in the gut microbiome can be detected in recent-onset pediatric MS (Tremlett et al. Eur J Neurol 2016;23:1308-1321). A pilot study found that depletion of one bacterial strain (Fusobacteria) was associated with an increased risk of relapse in MS patients (Tremlett et al. J Neurol Sci 2016;363:153-157). The group recently hosted a multidisciplinary workshop to discuss a Brain Health and the Microbiome initiative (McKay et al. Mult Scler Relat Disord 2017;12:1-3).
For a recent review of the topic see Glenn & Mowry. J Interferon Cytokine Res 2016;36:347-357. Free full text at www.ncbi.nlm.nih.gov/pmc/articles/PMC5118957/pdf/jir.2015.0177.pdf.