Bowel and Brain in Multiple Sclerosis

In recent years the information on the role of gut commensal microorganisms in immunological reactions has fully changed. Essential for MS research was the report by Turnbaugh et al.⁽¹⁾ that a representative animal model of the human gut eco-system was established, by transplanting fresh adult human faeces microbial communities into germ-free C37BL/6J mice.

Switching from low-fat, plant polysaccharide-rich diet to a high-fat, high sugar "Western” diet shifted the structure of the microbiota of these "humanized” mice in a single day and changed the metabolic pathways in the micro biome and its gene expression. "Humanized” mice fed "Western” diet have increased adiposity; this trait being transmissible via microbiota transplantations.

These findings were followed by work on EAE in germ-free mice induced for EAE ⁽²⁾. They produced lower levels of proinflammatory cytokines IFN-y and IL17 in both intestine and spinal cord and displayed reciprocal increase of CD4CD25Foxp3 Tcells (Tregs). Innate dendritic cells from germ-free animals have a reduced capacity to induce Th1 an Th17 cell responses to self-antigen.

Some microbe families from the gut microbiota however promote the inflammatory cascade in the CNS, as was recently shown. The strongest here being the unculturable Clostridium family of whichthe Segmented Filamentous Bacteria (SFB) is the most active ^(3).

It has been suggested over more than a decade that micro organisms contribute to the pathogenesis of MS⁽⁵⁾, culminating in recent experimental⁽⁶⁾ and clinical trials with antibiotic treatments^(7,8) or as additions to disease modifying treatments^(9,10).

^1. P.J. Turnbaugh et al. Sci.Translat.Med, 1:14 2009
^2. Yun Kyung Lee et al. PNAS 2010
^3. V. Gaboriau-Routhiau et al. Immunity 31 2009
^4. H. Klaassen et al. Infection and immunity 1993
^5. F. Gay The Journal of Neurol.Sci. 262 2007
^6. J. Ochoa-Repàraz et al. J.Immunol. 183 2009
^7. R.K. Zabar et al. Multiple Sclerosis 13 2007
^8. S. Guarnaccia Multiple Sclerosis 16 2010
^9. A. Minagas et al. Arch.Neurol. 65 2008
^10. L.M. Metz et al. Multiple Sclerosis 15 2009
^11. J. Correale et al. J.Neuroimm. 2011
^12. J.O. Fleming et al. Multiple Sclerosis 2011