The bacterial parasite Mycobacterium avium subspecies paratuberculosis (MAP) may trigger multiple sclerosis (MS), according to a new systematic review and meta-analysis published in Multiple Sclerosis and Related Disorders.

“Future studies on the role of MAP in the progression or severity of MS from one stage to another or phenotypes are highly imperative,” the authors said who also suggest that the implementation of a MAP screening could be useful to improve early management and treatment of MS.

To conduct the study, they selected data from 6 databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. They analyzed anti-MAP antibodies data from 12 studies and MAP DNA data from 4 studies.

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The study found an association between anti-MAP antibodies and MS risk, supporting the role of MAP as an environmental trigger. The odds ratios (ORs) were 10.71 (95% CI, 7.78-14.74, z=14.55, P <.0001) and 12.76 (95% CI, 8.13-20.02, t=12.43, P <.0001) in the fixed-effects (FE) and random-effects (RE) meta-analytic models, respectively. The I2 value, which was used to measure between-study heterogeneity, was 34.9% (95% CI, 0.0%-67.2%, P =.11).

Similar conclusions were drawn considering MAP DNA. The ORs were 5.53 (95% CI, 3.54-8.66, P <.0001) and 5.27 (95% CI, 3.22-8.60, P =.0017) in the FE and RE meta-analytic models, respectively. The I2 value was 0.0% (95% CI, 0.0%-84.7%, P =.71).

All RE meta-analytic sensitivity analyses indicated that MAP is a contributory environmental trigger for the development of MS. Moreover, p-curve distribution analysis highlighted a connection between MAP and a high risk of MS with significant statistical power of ≥94%. Results from Egger’s test pointed towards a publication bias in anti-MAP antibodies data, but not in MAP DNA data.

“The evidence of publication bias with anti-MAP abs [antibodies] meta-analysis could be attributed to study(ies) that reported optical density(ies) of MAP abs in MS patients/[controls] without accounting for the corresponding prevalence data,” the authors said.


Ekundayo TC, Olasehinde TA, Falade AO, et al. Systematic review and meta-analysis of Mycobacterium avium subsp. paratuberculosis as environmental trigger of multiple sclerosis. Mult Scler Relat Disord. 2022;59:103671. doi:10.1016/j.msard.2022.103671