News Researchers Pinpoint Signal that Triggers the Beneficial Effects of Specific Gut Bacteria in MS-Like
August 4, 2014
Researchers funded by the National MS Society have pinpointed a molecular signal that triggers the beneficial effects of gut bacteria in mice with MS-like disease. If continued research confirms and extends these findings to people who have MS, the results may present a novel target for a therapeutic strategy that “resets” the immune system to stop immune attacks in MS. Yan Wang PhD, Lloyd Kasper, MD (Dartmouth College, Hanover, NH) and colleagues report their findings in Nature Communications. (2014 Jul 21;5:4432)
Background: MS involves immune-system attacks against the brain and spinal cord. The gut, including the small and large intestine, is the largest immune organ in mammals. Each of us has millions of “commensal” bacteria living within our guts. Most of these bacteria are harmless as long as they remain in the inner wall of the intestine. They play a critical role in our normal physiology, and accumulating research suggests that they are critical in the establishment and maintenance of immune balance by the molecules they release. These molecules are absorbed by the complex structure of immune cells that are contained in the immune tissue associated with the gut.
Lloyd Kasper, M.D., is funded by the National MS Society, with underwriting support from the Conrad N. Hilton Foundation, to examine the effects gut commensal bacteria in MS and in mice with MS-like disease. Specifically, his team is looking at a molecule called polysaccharide A (PSA) that is released by specific species of gut bacteria (Bacteroides) that colonize almost 95% of people worldwide. Previous work in the Kasper lab (Mucosal Immunology. 2010 Sep;3(5):487-95) showed that PSA can reduce the effects of EAE, an animal model of MS, by stimulating the production of immune cells that regulate inflammation (known as Tregs). In this study, Dr. Kasper’s team investigated how bacterial PSA affects specific Tregs via an immune system protein (known as Toll-like receptor 2, or TLR2) in mice with EAE.
The Study: Dr. Kasper’s team administered PSA to mice six days before inducing EAE, until nine days after EAE induction. They then analyzed which immune system signals contributed to PSA’s beneficial effects.
The results show that bacterial PSA could expand a subset of Tregs that expresses the protein CD39. This expansion was dependent on TLR2. Signals from the protein CD39 were critical for the protective effects of PSA. CD39 was essential for the function of Tregs. When CD39 was deleted from mice, PSA was not able to control inflammation, and the ability of disease-causing immune cells was enhanced.
Conclusion: This study presents exciting findings on how gut bacteria may be able to modulate the immune attack in MS. If the results are confirmed in further study, CD39 may present a possible target for treatments that can stop the immune attack and enhance the protective capability of T regs. Ultimately, this could lead to the testing of an oral treatment that provides beneficial bacteria to reset the immune system in people with MS.
Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.