The association between antimicrobial exposure and subsequent multiple sclerosis risk: A systematic review and...

Multiple Sclerosis (MS) is a complex autoimmune inflammatory disease of the central nervous system with an incompletely understood etiology. Emerging evidence suggests a critical link between gut microbiome disruption and MS pathogenesis, with antibiotics potentially playing a significant role in microbiome alterations. We conducted a systematic review and meta-analysis to explore the relationship between antimicrobial exposure and the risk of developing MS.

A comprehensive systematic review was conducted across four electronic databases, searching for studies until March 29, 2025. The meta-analysis included comparative studies examining antibiotic usage frequency prior to MS onset/diagnosis in MS patients versus control group. Adjusted odds ratios (OR) were pooled using the generic inverse variance method with corresponding 95% confidence intervals (CIs).

The analysis encompassed nine reports involving 109,784 participants (23,960 MS patients and 85,824 controls). A statistically significant association was observed between antibiotic exposure and MS odds (OR=1.18; 95% CI [1.03-1.36]; p = 0.02). Data source-based analysis showed that studies with high-quality registry data maintained the association (OR=1.36; 95% CI [1.17-1.58]; p < 0.0001). Time-trend analysis showed significant association when the exposure occurred ≥4 years prior MS onset/diagnosis (OR=1.26; 95% CI [1.19-1.33]). Stratified analysis revealed significant associations for multiple antimicrobial classes, including tetracyclines, macrolides, quinolones, nitrofurantoin, aminoglycosides, metronidazole, sulfonamides, and antimycotics.

This meta-analysis reveals a significant association between antimicrobial exposures, particularly those based on high-quality data and occurring at least four years prior to MS onset/diagnosis, and increased MS incidence. Longitudinal, prospective studies are required to conclusively determine whether antibiotic exposure is a true risk factor for MS.