Study offers new clues to how gut bacteria may influence MS risk

Certain gut bacteria may influence the odds of developing multiple sclerosis (MS), in part by altering the activity of specific immune cells, according to an analysis of data from tens of thousands of people.

While the findings point to possible biological mechanisms linking gut bacteria and MS, the associations reached only nominal statistical significance and did not remain significant after correction, meaning they should be viewed as exploratory and interpreted with caution, according to researchers in China.

“The results are exploratory and hypothesis-generating only, serving to provide tentative clues for future research rather than definitive conclusions,” researchers wrote in the study, “Immune Cells as Mediators Between Gut Microbiota and Multiple Sclerosis: Insights From Mendelian Randomization,” which was published in Immunity, Inflammation and Disease.

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MS occurs when the immune system mistakenly attacks the protective covering of nerve fibers, causing inflammation and damage in the brain and spinal cord.

Both gut bacteria and immune cells are thought play important roles in MS, and researchers increasingly suspect that interactions between gut microbes and the immune system contribute to MS, but exactly how gut bacteria might influence disease risk remains unclear.

To explore further, the researchers used a method called Mendelian randomization, which relies on naturally occurring genetic differences to investigate whether one factor is likely to influence another.

In particular, the team examined genetic variants that are associated with certain bacteria or immune cell traits. They then tested whether those same genetic variants were also linked to MS, helping them estimate whether the bacteria or immune traits might influence the risk of MS.

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After identifying gut bacteria and immune traits that showed potential links to MS, the researchers looked at whether changes in immune cells might partly mediate the relationship between gut bacteria and the disease.

The scientists analyzed data on gut microbiota — the community of microorganisms that live in the gut — from 18,340 people, along with data on immune cell traits from 3,757 people in Sardinia, Italy. They then compared those data with genetic information from 47,429 people with MS and 68,374 people without the disease from the International Multiple Sclerosis Genetics Consortium.

The analyses identified six groups of gut bacteria that showed possible links with MS. Four appeared to be associated with lower odds of developing the disease, while two were linked to higher odds. However, after correcting for multiple statistical tests, none of these links remained significant, meaning they should be considered exploratory.

The researchers also identified 52 immune traits that showed associations with MS, but again, none remained significant after statistical correction.

Resulsts ‘need to be interpreted with caution’

To explore whether immune cells may help explain the link between gut bacteria and MS, the researchers focused on the six groups of bacteria and the 52 immune traits identified in the earlier analyses. Mediation analysis, which looks for an intermediate behind a relationship, suggested two possible pathways.

One involved Roseburia bacteria and CD28, a protein found on the surface of some T-cells that help coordinate immune responses. The analysis suggested that about 9% of the estimated association between Roseburia and MS could be explained through CD28 levels on these immune cells.

The second pathway involved Ruminococcus 2 bacteria and CD45, a protein found on another group of T-cells that normally help eliminate infected or abnormal cells. In this case, the immune trait accounted for about 12% of the estimated association between the bacteria and MS.

Together, the findings suggest that specific T-cell characteristics may contribute to the relationship between gut bacteria and MS. However, the immune traits explained only a small proportion of the estimated effects, indicating that additional mechanisms are also likely involved.

However, because none of the associations remained statistically significant after correction, “these results only represent exploratory trends and need to be interpreted with caution,” the researchers wrote.

They said the proposed pathways will need to be validated in independent groups of people and preclinical studies before conclusions can be drawn.