Gut bacteria at MS diagnosis offer early clues to disease course

Changes in the gut microbiome — the community of bacteria and other microorganisms that live in the digestive tract — at the time of a multiple sclerosis (MS) diagnosis may offer early clues about how the disease will progress, a study suggests.

Researchers found significant differences in the overall gut microbiome between people newly diagnosed with MS and healthy controls. They also identified bacterial patterns associated with MRI features linked to a less favorable MS prognosis.

When these patterns were analyzed together, they revealed two clinically distinct patient groups, one of which showed a greater tendency toward disease progression over the following year.

“Gut microbial profiling may therefore represent a promising early prognostic biomarker and may help to identify candidate targets for early intervention and therapeutic development in MS, although further validation in larger longitudinal [groups] is needed,” the researchers wrote.

The study, “Gut microbiome profiling at multiple sclerosis onset as a potential early prognostic marker of disease course: evidence from an observational cohort study,” was published in eBioMedicine.

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Gut microbiome differences

While the exact causes of MS are currently unknown, the gut microbiome has increasingly been linked to the disease. Previous studies have found that the gut microbiome differs between people with MS and healthy individuals.

However, much research has involved people with established MS or those receiving disease-modifying therapies (DMTs), which can alter the gut microbiome. Few studies have examined microbiome composition at disease onset, before DMT exposure, or its potential effects under glucocorticoid immunosuppressive therapy used to manage acute MS symptoms.

To address these gaps, researchers in Italy conducted comprehensive analyses of stool samples from 53 adults with MS and 55 healthy controls, recruited across four centers from 2017 to 2023. MS patients had been recently diagnosed, had not yet received DMTs, and had no reports of recent antibiotic use, which also changes the gut microbiome.

Stool sample analyses enabled determination of each person’s gut microbiome at the species level. Researchers also collected clinical and MRI data at MS diagnosis and followed patients for one year.

MS participants had a mean age of 35, and 60% were women. Healthy controls had a similar age and sex distribution.

Overall, the gut microbiome differed significantly between people with MS and healthy controls.

Within the MS group, glucocorticoid treatment at disease onset was the clinical factor most strongly associated with gut microbiota diversity.

The researchers accounted for its potential effects in subsequent analyses of bacteria associated with MRI features linked to a less favorable prognosis. These features included high lesion burden, the presence of spinal cord lesions, infratentorial lesions (which affect the lower parts of the brain), and active inflammatory lesions.

Forty-six bacterial species were associated with at least one of these features. Six of these species also consistently differed between people with MS and healthy controls. Two Bacteroides species were less abundant in MS patients and were further reduced in those with a high lesion burden and those with infratentorial lesions.

By contrast, Barnesiella sp. An22 and Romboutsia ilealis were more abundant in the MS group and associated with a higher lesion burden. Clostridium innocuum and Ruminococcus sp. JL13D9, also more abundant in MS patients, were associated with spinal cord lesions.

The researchers said the loss of the Bacteroides species may reflect reduced anti-inflammatory and neuromodulatory functions, while increases in C. innocuum and Ruminococcus were more consistent with an inflammatory imbalance in the gut microbiota.

Analyzing together the bacterial signatures associated with these MRI features separated patients into two groups. The team then analyzed whether these gut microbiome-based groups showed differences in the risk of disease progression within 12 months.

Disease progression was defined as an increase of at least 0.5 points on the Expanded Disability Status Scale, which measures MS-related disability, new lesions on MRI scans, or a disease relapse within one year.

They found that one group showed a trend toward a lower risk of disease progression. But the difference between the groups did not reach statistical significance, meaning it could be due to chance.

The groups did differ significantly in their clinical features at diagnosis, with motor symptoms and spinal cord lesions being significantly more common in the group with the less favorable prognosis.

The researchers noted that both features have previously been linked to faster disability accumulation and poorer long-term MS outcomes, supporting the clinical relevance of the microbiome-based grouping.

“Our study proposes gut microbiota analysis as a potential prognostic factor for MS at diagnosis, since we revealed a peculiar gut microbiome profile in individuals with a more severe disease course,” they wrote, and gut microbiome profiling “could contribute to the therapeutic decisional process aimed to identify as soon as possible those patients at higher risk of a negative disease course.”