To assess whether leptomeningeal enhancement (LME) and cortical lesions (CL) burden are associated with the gut microbiome and stool mucus levels in individuals with MS.

LME and CL are features of MS that have been linked to disease progression and are visualized on brain 7T magnetic resonance imaging (MRI) with high sensitivity. Gut microbiota play a role in MS pathogenesis, and the presence of microbial correlations with disease phenotype, EDSS and other clinical characteristics suggests that gut microbiota may also influence MRI findings.

A total of 28 MS subjects [age (mean ± SD): 53.4 ± 13 years] underwent gadolinium-enhanced three-dimensional magnetization-prepared 2 rapid gradient-echo (MP2RAGE) and fluid-attenuated inversion recovery (FLAIR) MRI at 0.7 mm³ voxel sizes. LME and CLs were expert-quantified. Within 6 months of MRI acquisition, stool samples were collected.

At a species level, differential abundance of the short-chain fatty acid producers Roseburia and Bifidobacterium was increased in individuals with lower LME foci count (MaAsLin2 coefficients= -0.65 and -0.56). Abundance of Alistipes onderdonkii positively correlated with LME foci count (MaAsLin2 coefficient= 0.80). Abundance of the mucin degrader Ruminococcus torques positively correlated with CL count (MaAsLin2 coefficients = 0.10 and 0.12), while Ruminococcus bicirculans was increased in individuals with lower total CL volume (MaAsLin2 coefficient= -3.03). Stool MUC2 levels negatively correlated with LME foci (Spearman coefficient= -0.47).

Individuals with a lower burden of LME and CL on 7T MRI had increased levels of potentially beneficial bacteria, while individuals with a higher burden of LME and CL on 7T MRI exhibited increased levels of potentially detrimental bacteria. These MRI-microbiome associations suggest a role of gut microbiota in modulating CNS meningeal inflammation and cortical demyelination. One potential hypothesis is thata decrease of the mucus layer which results in a narrow bacterial-immune system interface may favor LME development and thereby cortical lesions.