Immune system-gut bacteria interactions altered in MS: Study
Interactions found to be affected by certain immune-modulating treatments
Interactions between the body’s immune system and bacteria that live in the digestive tract — essentially, a person’s gut — become disrupted in multiple sclerosis (MS), a new study by U.S. researchers found.
The human intestines are home to billions of bacteria and other microorganisms, collectively known as the gut microbiome. These bacteria normally play important roles in health, including the regulation of the body’s immune responses.
However, new research by scientists at Yale University School of Medicine and the Mayo Clinic found alterations in these interactions in the gut in people with MS. The team also discovered that certain immune-modulating MS treatments may affect these relationships.
According to the researchers, the findings highlight “shifts in gut microbial [types] induced by immune [changes] in MS, suggesting the potential for leveraging these changes as biomarkers or therapeutic targets.”
Their study, “Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis,” was published in the journal Neurology Neuroimmunology and Neuroinflammation.
Scientists used stool samples from patients, controls to analyze gut microbiome
Studies have previously shown that the gut microbiome becomes dysregulated in MS, but there hasn’t been much investigation specifically into how the interaction between gut bacteria and the immune system is affected.
“Although gut microbiome [disruption] is now recognized in MS, the interactions between the gut microbiome and the host’s immune response to this disease remain largely unexplored,” the researchers wrote.
Now, the team of researchers specifically looked at how MS affects the number of gut bacteria that are coated with immunoglobulin A (IgA) antibodies.
Antibodies are proteins made by the immune system to help combat potential threats. Immune cells in mucus-coated organs, including the intestines, release a specific type of antibody called IgA that binds to certain types of gut bacteria, limiting their movement and/or leading to their death.
The study included 43 people with newly diagnosed, untreated MS, as well as 42 age- and sex-matched healthy people, who served as controls. Stool samples were collected from all participants to analyze the gut microbiome and the proportion of IgA-coated bacteria.
The results showed significant differences in the types of bacteria making up the gut microbiome between individuals with or without MS, which is generally consistent with previous reports.
[These findings suggest] that there is perhaps a fundamental disconnect going on with the host-microbe interactions [in the gut microbiome in MS].
Further, the MS patients had significantly fewer bacteria coated with the IgA antibodies, as noted by Erin Longbrake, MD, PhD, the study’s cosenior author and an associate professor of neurology at the Yale School of Medicine.
That “suggests that there is perhaps a fundamental disconnect going on with the host-microbe interactions,” Longbrake said in a university news story.
Significant differences found in specific gut bacteria after MS treatment
After the initial analyses, 19 of the MS patients (44%) started treatment with CD20 inhibitors. This type of MS treatment works to deplete B-cells, the immune cells that are responsible for making antibodies.
After a few months of such treatment, new stool samples from these patients were collected by the researchers, who sought to determine how the use of CD20 inhibitors was affecting IgA coating in the gut microbiome.
The team found that the proportion of bacteria that were coated with IgA was not affected by CD20 inhibitors. However, when the researchers looked at the results in more detail, they found that there were significant differences in specific bacteria types.
The analysis “identified specific organisms where IgA-coating patterns were lost following B-cell-depleting therapy, as well as organisms whose IgA-coating patterns shifted to align more closely with controls,” the researchers wrote.
According to the team, this “work illustrates that the host response to the gut microbiome, including relationships between [IgA-coated] and total gut bacteria, is dysregulated in early-stage MS, building on previous work where decreased proportions of [IgA-coated] gut bacteria were associated with high levels of physical disability and recent clinical relapses.”
These findings mean that such MS-related changes have the potential to be used as markers of disease activity or targets of new treatments, the researchers noted. However, per the team, further analyses of IgA-gut bacteria interactions over time in MS are needed to further inform the potential utility of these results.
“We’re still analyzing what our results mean and how we can use this information to improve care,” Longbrake said. “These are areas to investigate in the future.”
The researchers’ work was supported by several awards from the National Institutes of Health.
About the Author
