Each person’s gastro-intestinal system is home to trillions of bacteria collectively known as the gut microbiota. These tiny creatures are essential partners in good health, and in less than a decade MS researchers have gone from considering the gut microbiota to be a curiosity to gathering evidence that disruption of the gut’s natural bacterial balance is linked to MS. A powerful method of studying the gut microbiota is to investigate the gut microbiome – the genetic composition of the microbiota. Unresolved questions about the gut microbiome persist, such as: Do people with MS have different microbiome “fingerprints” than people without MS? Does the gut microbiome play a functional role in modifying MS risk and/or disease course? Does the gut microbiome represent a potential therapeutic target in MS? Leaders in the field of MS and gut microbiome research here at ACTRIMS 2017 presented some of the latest findings that tackle these questions.
Renowned MS researcher Dr. Howard Weiner (Harvard Medical School) presented findings from an exploratory study that measured and compared the gut microbiome in 60 people living with MS and 43 healthy controls. His team found that people with MS had a unique microbiome “signature”, set apart by increases in the bacterial genus Methanobrevibacter and Akkermansia, and a decrease in Butyricimonas. Importantly, these changes in the gut microbiome profile correlated with the expression of genes in T cells and monocytes involved in key pathways linked to the MS disease process, which suggests that changes in the microbiome may help to trigger or drive MS, although it’s still not known if these changes are a cause or consequence of the disease. Another interesting finding was that elevated methane was detected in a certain proportion of the MS group, which is thought to be linked with increased Methanobrevibacter presence in the gut; future studies could investigate whether breath methane could be used as an easy-to-collect biomarker for MS.
Dr. Weiner also presented preliminary data from a study examining the effect of probiotics on the gut microbiome and its potential implications for MS. In a clinical context, probiotics are live, non-toxic micro-organisms that are being actively investigated for their potential benefits in health and disease. Dr. Weiner described a small pilot study in which 9 participants with MS and 13 healthy controls were orally administered VSL#3, a probiotic which has shown evidence of potential benefits in mice with an MS-like disease by both encouraging anti-inflammatory and discouraging pro-inflammatory immune responses. After being administered twice daily for 2 months, VSL#3 changed the relative composition of the gut microbiota compared to before treatment, which was accompanied by a decrease in peripheral levels of pro-inflammatory immune cells and signaling molecules in both the MS and healthy control groups. Discontinuation of VSL#3, on the other hand, was associated with a decrease in the levels of anti-inflammatory regulatory T cells. These findings, while promising, are still very preliminary, and larger studies looking at MS-specific clinical and imaging outcomes will be necessary to probe the potential benefits of probiotics like VSL#3.
Since children and adolescents in general have had fewer environmental and lifestyle exposures in life compared to adults, including exposure to diets, infections and so on, the study of the gut microbiome in pediatric MS offers a unique window in which to explore the possible triggers or modifiers of the disease. MS Society-funded researcher Dr. Helen Tremlett (University of British Columbia) presented findings from two studies probing the relationship between gut microbiome and pediatric MS. The first, a case-control study conducted by Dr. Tremlett and Dr. Emmanuelle Waubant (University of California San Francisco), compared the gut microbiota in 18 cases of new-onset pediatric MS and 17 healthy controls. They found that children with MS had subtle differences in the gut microbiota that were suggestive of a pro-inflammatory profile compared to those without MS. However, the study was not designed to answer the question of whether the gut microbiota can influence MS relapses. To answer this question, a second study examined children with early pediatric MS over time to determine if specific gut microbiota “signatures” are associated with subsequent relapse risk. Dr. Tremlett and her team found that the composition of the gut microbiota in children with MS was associated with relapse risk; specifically, individuals lacking one particular genus of gut microbe – Fusobacteria – were 3.2 times more likely to suffer an earlier relapse than individuals who tested positive for the bacteria. Although these observations warrant more research, they may pave the road for modifiable targets to improve outcomes in both pediatric and adult MS. Dr. Tremlett is continuing this important work with funding from the MS Society-affiliated MS Scientific Research Foundation in collaboration with the Canadian Pediatric Demyelinating Disease Network and the US Network of Pediatric MS Centers.
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