The role of viral infections and other microbial factors in the pathogenesis of multiple sclerosis: a systematic review.
TL;DR
Microbial exposures, particularly EBV-related immune responses, play a significant role in MS pathogenesis and further research should focus on interactions between infections, host genetic predisposition, and immune dysregulation in MS.
Abstract
Background
The aetiology of multiple sclerosis (MS) is complex and remains unclear. Increasing evidence suggests that environmental factors, including infectious agents, may contribute to disease initiation and progression. This review aims to summarize current evidence on the role of microorganisms in MS pathogenesis.
Methods
A systematic literature search was conducted in PubMed, SCOPUS, and Web of Science. We enrolled studies published between 2020 and 2025. Eligible papers investigating associations between microbial agents and MS risk, activity, or progression were assessed for eligibility. Sixty-one studies were included.
Results
The examined studies demonstrated that Epstein-Barr virus (EBV) seropositivity is nearly universal among MS patients, with elevated anti-EBNA-1 antibody titers and a strong association between infectious mononucleosis and MS development. Associations with other herpesviruses are less consistent. Human herpesvirus-6 may contribute to disease activity and interact with EBV-related immune responses. Evidence regarding herpes simplex virus and varicella-zoster virus remains inconclusive. Several studies suggest that cytomegalovirus infection may exert a protective effect. Human endogenous retroviruses may amplify inflammatory responses and coexist with EBV-driven immune activation. Evidence for bacterial pathogens, such as Chlamydia pneumoniae, Mycobacterium tuberculosis, and Staphylococcus aureus, indicates possible associations with MS, although available studies are limited. The protective effect of Helicobacter pylori has not been confirmed. No clear relationship has been established for fungal or parasitic infections.
Conclusion
Microbial exposures, particularly EBV-related immune responses, play a significant role in MS pathogenesis. Further research should focus on interactions between infections, host genetic predisposition, and immune dysregulation in MS.