Diet quality, gut microbiome diversity, and clinical disability in multiple sclerosis: A cross-sectional case-control study

Dietary patterns and gut microbiome composition are increasingly recognised as modifiable factors in multiple sclerosis (MS). We aimed to evaluate dietary quality, microbiome diversity, and their inter-relationships with MS status, clinical disability, and disease-modifying therapy (DMT). We compared 288 MS cases with 274 household healthy controls (HHC). Dietary intake was assessed using healthy eating index (HEI-2015), and the groups were compared and associations analysed using multivariable linear regression. Among all HEI-2015 components, only total fruit intake was significantly higher in MS (β=+0.46; 95% CI: +0.19 to +0.74; FDR q = 0.014). Higher HEI-2015 scores were positively associated with greater Shannon alpha diversity (β=+0.077/10-unit increment; 95% CI: +0.003 to +0.150; p = 0.042). The PERMANOVA revealed independent association between microbiome beta diversity and smoking (R²=0.011; p = 0.007), BMI (R²=0.007; p = 0.010), age (R²=0.006; p = 0.027), and MS status (R²=0.005; p = 0.026), but not with diet quality (R²=0.006; p = 0.171). The whole grains consumption was directly associated with EDSS (FDR q = 0.033). Microbial richness differed across DMT categories (p = 0.001), and mechanism-level analysis attributed this to natalizumab, anti-CD20 therapy and dimethyl fumarate. In conclusion, higher fruit intake and dietary quality positively were related to gut microbiome diversity in MS. Disease status, smoking, and BMI are the primary drivers of microbiome community composition. Therefore, dietary modification could be a potential adjunctive strategy in MS management.