Gut Microbiome Composition May Help Predict Treatment Side Effects
Tecfidera led to decreases in levels of two types of bacteria, increases in another
Differences in the composition of the gut microbiome are associated with an altered risk of low immune cell counts as a side effect of treatment with the multiple sclerosis (MS) therapy Tecfidera (dimethyl fumarate).
The findings provide further insights on how the gut microbiome — the billions of bacteria and other microscopic organisms in the human digestive tract — can influence the clinical and adverse effects of certain MS therapies.
The study, “Gut microbiota composition as a candidate risk factor for dimethyl fumarate-induced lymphopenia in multiple sclerosis,” was published in Gut Microbes. The work was funded in part by Biogen, which markets Tecfidera, an oral therapy that’s widely approved to treat relapsing forms of MS and is thought to reduce the inflammatory attack that drives the disease. In addition to the name-brand therapy sold by Biogen, several generic versions are available in the U.S. and elsewhere.
The gut microbiome plays essential roles in human health and disease, many of which are only starting to be understood. Tecfidera is often associated with gastrointestinal side effects, but few studies have assessed how this and other MS therapies may alter the gut microbiome.
Researchers assessed the gut microbiome in 20 people with relapsing-remitting MS (RRMS) who were starting on Tecfidera. Most were women (55%) and with a median age of 42.
Gut microbiomes were analyzed before starting Tecfidera (baseline), then again after three months and one year on the therapy.
Results showed it led to a significant decrease in levels of two species of bacteria, Coprococcus eutactus and Enterococcus gilvus. Levels of another bacterial species called Lactobacillus pentosus were significantly increased after treatment.
The researchers noted that levels of taxa (groups of bacteria) associated with promoting inflammation tended to decrease with Tecfidera, though most results weren’t statistically significant. Levels of taxa thought to have anti-inflammatory properties tended to increase after treatment.
“Our findings demonstrate a specific rearrangement of MS-associated taxa upon [Tecfidera] treatment with a decrease in MS-associated proinflammatory taxa … and an increase in allegedly beneficial, anti-inflammatory species,” the researchers wrote.
“Our data suggest that immunomodulatory therapies affect not only immune cells, but also positively influence the gut microbiome,” said Anne-Katrin Pröbstel, MD, PhD, a study co-author at University of Basel, Switzerland, in a university press release.
One of the common side effects of Tecfidera is lymphopenia, when levels of certain immune cells are lower than normal, which can raise the risk of serious infection. In subsequent analyses, the researchers noticed patients who developed lymphopenia after starting Tecfidera had distinct features in their gut microbiomes at baseline, compared with those who didn’t develop it.
Specifically, patients with the bacterial species Akkermansia muciniphilia in their gut microbiome, but not the species called Prevotella copri, were more likely to develop lymphopenia, results showed.
“In turn, lymphopenia was absent in patients with simultaneous appearance of both A. muciniphila and P. copri, indicating a possible counteracting effect by the presence of P. copri,” the team wrote, emphasizing that more research was needed to validate and expand their findings.
They said their results suggested analyzing the gut microbiome could improve personalized treatment in MS.
“In the future, this relatively new field of microbiology may help us better understand the effects and side effects of many medications with regard to gut bacteria, and to personalize treatment accordingly,” said study co-author Adrian Egli, MD, PhD, of the University of Zurich.