Gut Bacteria Are Altered in MS, Linked to Disease Progression
Higher levels of inflammatory bacteria, lower levels of good bacteria observed
The composition of bacteria in the gut is altered in multiple sclerosis (MS) patients compared with healthy people in the same household, a new study reports.
That bacterial composition is affected by disease-modifying therapies and seems to be associated with disease severity. These findings could aid in developing new therapies to regulate the MS gut microbiome.
The study, “Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course,” was published in Cell.
The human digestive tract is home to billions of bacteria and other microorganisms, collectively called the gut microbiome. An emerging field of research has shown that gut bacteria play important roles in health and disease.
Some studies have shown alterations in the gut microbiome in MS patients, but specific results are often inconsistent from study to study. One likely reason for this is that the composition of the gut microbiome is heavily affected by environmental factors, such as where a person lives and what they eat.
The International Multiple Sclerosis Microbiome Study (iMSMS) sought to overcome these limitations by comparing the gut microbiome of people with MS to that of people without MS from the same household, meaning environmental factors are largely comparable.
“This is the reference study that will be used by the field for years to come,” Sergio Baranzini, PhD, the study’s lead author from the University of California San Francisco, said in a university press release.
The study included 576 pairs of MS patients and genetically unrelated household controls. Among the MS patients, 76% had relapsing-remitting disease (RRMS) and 24% had progressive types of MS. About two-thirds of the MS patients were being treated with a disease-modifying therapy.
Gut microbiome content was determined by analyzing stool samples with a technique called 16S rRNA sequencing, which involves using a specific bacterial genetic sequence as a “barcode” to identify which species of bacteria are in a sample.
In line with prior work, results showed location of residence was the largest source of variation in microbiome content, but age, sex, and other demographic factors were also linked with changes.
After accounting for these differences, the researchers identified 16 species of bacteria present at significantly higher amounts in MS patients compared with controls, and seven species at lower levels in patients than controls.
“We were surprised by the number of species that were differentially present in MS when compared to controls,” Branzini said.
Several of the identified species have known properties that could theoretically contribute to MS, which is caused by inflammation in the brain and spinal cord.
For example, one of the species that was decreased in MS patients — Faecalibacterium prausnitzii — is known to have anti-inflammatory properties. Metabolic pathway analyses showed corresponding disease-relevant changes (e.g., reductions in the production of pyruvate, a molecule that F. prausnitzii helps make).
“We found a depletion of potentially beneficial bacteria in untreated MS patients compared with healthy controls, which in turn disturbed key metabolic pathways that might be expected to worsen MS inflammation.
These findings could aid in developing “designer probiotics” to make MS gut microbiome composition healthier, the scientists speculated, but emphasized that more research is needed to untangle the specific roles of individual species.
“When looking at the microbiome, there are two questions that usually are asked,” Branzini said. “The first one is ‘Who’s there?’ This is what we’re trying to answer in this paper. The second is, ‘What are they doing?’”
Some of these bacterial species were associated with differences in disease severity, analyses showed. For example, among progressive MS patients, the bacteria Butyrivibrio, Clostridium, and Ruminococcus were associated with less severe disease, while bacteria in the group Prevotella were linked with more severe disease.
In RRMS patients, some bacteria in the group Bacteroides were associated with less severe disease scores, while the species Collinsella aerofaciens was associated with more severe disease.
Gut bacteria also differed based on MS treatment. For example, certain bacterial species in the group Akkermansia were altered (compared to respective household controls) in untreated RRMS patients, but not in RRMS patients on disease-modifying treatment.
In some cases, different MS therapies had disparate effects on gut bacteria. For example, levels of the bacteria Bacteroides uniformis were increased in patients on interferon therapies, but decreased with Tysabri (natalizumab) or glatiramer acetate (sold as Copaxone, among others).
“Overall, our findings revealed a robust alteration of gut microbial composition related to the disease and therapy,” the scientists wrote.