Immune Cells as Mediators Between Gut Microbiota and Multiple Sclerosis: Insights From Mendelian Randomization

Multiple sclerosis (MS) is a neuroimmunological disorder marked by demyelination and neuronal damage, significantly impacting young individuals' health and quality of life. Recent studies suggest a pivotal role of the gut microbiota and immune system in MS development, though the precise mechanisms remain unclear.

This study utilizes Mendelian randomization (MR) to explore the causal relationships between gut microbiota, immune traits, and MS. We conducted MR analysis using genetic data from 18,340 participants for gut microbiota, 3757 individuals for immune traits, and 47,429 MS cases alongside 68,374 controls.

Our results suggested six microbial taxa with nominally significant associations to MS, with two taxa (Roseburia and Ruminococcus2) exhibiting putative mediating trends through specific immune cell phenotypes (CD28 on CD28⁺ CD4⁺ T cells and CD45 on HLA-DR⁺ CD8⁺ T cells). Mediation analysis demonstrated that 8.97% and 12.18% of the nominal effects of these taxa on MS were potentially mediated through the aforementioned immune traits, respectively. These results only represent exploratory trends and need to be interpreted with caution.

These nominally significant exploratory findings provide hypothesis-generating clues that immune cell activation, particularly in CD4⁺ and CD8⁺ T cells, might be involved in the microbiota-MS relationship. These findings require validation in independent populations and experimental studies.