Center for Precision Medicine Research publishes research toward understanding cause of multiple sclerosis
Sanjay Shukla, Ph.D., Director of Marshfield Clinic Research Institute's Center for Precision Medicine Research and his colleagues published a manuscript on their research toward understanding the cause of multiple sclerosis in the peer-reviewed journal, Scientific Reports, entitled, “Genetic risk score in multiple sclerosis is associated with unique gut microbiome."
Multiple sclerosis is a chronic, inflammatory, autoimmune disease of the central nervous system and a leading cause of disability in young adults between 20 and 50 years of age. It is affecting about 450,000 Americans and 2.8 million people worldwide and its numbers are increasing, according to a paper published in the Multiple Sclerosis Journal. 
The cause, or etiology, of multiple sclerosis is complex, which includes genetic susceptibility, environmental factors including viral infection, low sunlight exposure, obesity and/or gut microbiota dysbiosis. Working with Paula Aston, M.D., a Marshfield Medical Center neurologist, Dr. Shukla and his team enrolled 240 cases and 50 healthy control subjects. Blood and fecal (surrogate for gut microbiome) samples were collected and genotyped to calculate genetic risk score for the cases and controls and perform microbiome analysis of the fecal samples.
Noha Elsayed, Ph.D., an Ebenreiter Postdoctoral Fellow working with Dr. Shukla showed that phylogenetic diversity of the microbiome of cases was significantly different than the controls. Also, the study showed that indeed multiple sclerosis patients had higher genetic risk score than the healthy, non-multiple sclerosis controls. Interestingly, in a small group of multiple sclerosis patients the higher genetic risk score was associated with a unique gut microbiome suggesting a potential interaction between these factors.
“Our research findings are exciting because it calls for further mechanistic studies as to how gut microbiome or it's metabolites could play a role in MS disease signaling pathways in genetically susceptible patients," said Dr. Shukla. “Hopefully in the future a treatment regimen could be developed that may include customized probiotics along with current treatments, but we are still very far from there."
Prior studies showed that both genetic factors and gut microbiome dysbiosis are independently associated with multiple sclerosis. In this pilot study, in a smaller cohort of patients, genetic risk score is associated with the gut microbiome dysbiosis. This group is further investigating the genetic risk score in a larger number of cases, and the associated roles of the gut virome and gut bacterial metabolites in triggering the symptoms of multiple sclerosis in genetic susceptible patients.
Dr. Shukla was appreciative of the multiple sclerosis patients and control subjects who consented to be part of the study and for providing clinical samples. He also thanked donors to Marshfield Clinic Research Institute and UW-Institute for Clinical and Translational Research for funding and Research Coordinator Terrie Kitchner for helping with enrollment and coordination of the project.