As the most widespread disabling neurological condition in young adults, multiple sclerosis (MS) affects approximately 1 million people in the United States and up to 2.3 million across the globe. Although researchers have not yet discovered the underlying causes of the condition or the reasons behind its unpredictable progression, there is an increased focus on the role of the gut microbiome in its development.
Prior research linking gut flora and multiple sclerosis has shown differences in the types of gut bacteria found in individuals with multiple sclerosis (MS). Patients with MS tend to have more archea – a microbe responsible for inflammation – and less butyricimonas – a microbe with anti-inflammatory properties – compared with individuals without the condition.
New research implicates that patients with multiple sclerosis exhibit changes in gut bacteria composition after being treated with the disease-modifying drug ocrelizumab (Ocrevus).
Effect of Medication on Gut Microbiome
Disease-modifying medications tackle MS by depleting B cells, leading researchers to hypothesize that ocrelizumab could normalize the phenotype and metabolic profiles of gut bacteria thereby promoting an anti-inflammatory immune environment. As part of the ongoing trial, the research team is enrolling patients with new-onset multiple sclerosis and evaluating longitudinal samples of paired blood and stool with advanced techniques – including IgA-Seq, a novel tool that allows the differentiation of immune-reactive bacteria from IgA-uncoated bacteria.
Changes in Gut Bacteria
According to preliminary findings from the ongoing study, the normalization of certain components of the fecal microbiome in MS patients occurred at 1 month after ocrelizumab treatment, compared with baseline measurements. The team’s initial results are based on a cohort of 8 patients with MS and 5 control group participants.
Several members of the MS group showed very high IgA-coated indices for selected bacteria in the butyrate-producing Lachnospiraceae family at baseline. Following ocrelizumab treatment, these patients showed a reduction in the IgA coating index for butyrate producers. Furthermore, butyrate was significantly decreased at baseline in the MS group compared with levels found in the healthy control group. However, these changes did not last and the difference in butyrate levels dissipated after treatment was ceased. No differences were observed in acetate and propionate values.
Implications of Bacteria Changes
“Our data suggest that a subset of butyrate-producing gut bacteria is recognized as pathogenic by the immune system of untreated MS patients, based on high levels of IgA coating,” the researchers told Medscape Medical News, “This phenomenon could impact the amount of butyrate produced and affect the differentiation of circulating immune cells.”
The reduction of the IgA coating index of butyrate-producing bacteria as a result of ocrelizumab treatment points to its potentially significant role in the efficacy of B-cell depletion in MS patients. “The data also suggest that “changes in the gut microbiota may comprise part of the mechanism of action for a variety of MS disease-modifying therapies, including ocrelizumab,” lead author Erin Longbrake, MD, PhD told Medscape Medical News.
Due to the small scale of the study, its results are difficult to generalize; however the preliminary findings add to a growing body of evidence supporting the critical relationship between the gut microbiome and multiple sclerosis pathology. The research team is currently enrolling additional participants to investigate this connection further and plans on expanding its analysis to include long-amplicon sequencing and metabolomic analysis.
With about 200 new cases of multiple sclerosis diagnosed per day in the United States, there is an acute need for a better understanding of its underlying mechanisms. Identifying how these changes in the gut microbiome occur and improving the understanding of the implications of pharmacologic therapies could lead to the development of more targeted, personalized interventions aimed toward correcting specific pathologic modifications.
