Systematic review and meta-analysis of Mycobacterium avium subsp. paratuberculosis as environmental trigger of multiple sclerosis

• Published in: Multiple sclerosis and related disorders Vol. 59; p. 103671
• Main Authors: Ekundayo, Temitope C., Olasehinde, Tosin A., Falade, Ayodeji O., Adewoyin, Mary A., Iwu, Chidozie D., Igere, Bright E., Ijabadeniyi, Oluwatosin A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2022
• Subjects: Animals; Autoantibodies; Autoimmune disorder; Humans; Multiple Sclerosis - etiology; Multiple Sclerosis - genetics; Mycobacterium avium subsp. paratuberculosis - genetics; Myelin damage; Neurodegeneration; Neuroimmune; Neuroinfection; Neuroinflammatory; Odds Ratio; Paratuberculosis - diagnosis; Paratuberculosis - epidemiology; Paratuberculosis - microbiology; Autoantibodies; Autoimmune disorder; Neurodegeneration; Neuroimmune; Myelin damage; Neuroinflammatory; Neuroinfection
• ISSN: 2211-0348; 2211-0356
• DOI: 10.1016/j.msard.2022.103671

•MAP (Mycobacterium avium subsp. paratuberculosis) has role in MS (multiple sclerosis).•Efforts channelled to unravel the role of MAP in MS is still limited.•A total of 2538 MAP-related MS patients’ data from 12 studies was meta-analysed.•MAP was associated with a significant risk of multiple sclerosis.•MAP and MS link valued at12.76 odds ratios (OR)(antibody) & 5.27OR (DNA).•Timely screening of MAP in MS cases may benefits therapeutics in its treatment. Mycobacterium avium subsp. paratuberculosis (MAP) has been identified as one of the environmental agents that causes multiple sclerosis (MS). The global prevalence of MS has been upsurging over the years; however, efforts to divulge the role of MAP in MS have been limited. As a result, the present study aimed at assessing the odd ratios (ORs) associated MAP with the risk of MS. MAP-related MS data were obtained from 6 databases using the terms 'multiple sclerosis' or 'MS' and 'paratuberculosis' without regard for time or language restrictions following PRISMA standards. A total of 2,538 participants' data from 12 studies presenting anti-MAP antibodies and MAP DNA from 4 studies were fitted in random-effects (RE) and fixed-effects (FE) meta-analytic models. Furthermore, the between-study heterogeneity was measured using I2-values with a significant limit set at an I² > 75%. Analytical rigor and publication bias was determined using leave-one-out-analytics, Egger's tests, and p-curve analysis. In the FE and RE models, anti-MAP antibodies data significantly associated MS risk with MAP as 10.71 OR (95%-CI [7.78; 14.74], p-value < 0.0001) and 12.76 OR (95%-CI [8.13; 20.02], p-value < 0.0001) respectively, with an I2 value of 34.9% (95%-CI [0.0%; 67.2%]; p-value = 0.11). Similarly, the MAP DNA dataset in FE significantly present MS risk due to MAP as 5.53 OR (95%-CI [3.54; 8.66], p-value< 0.0001) while, RE showed 5.27 OR (95%-CI [3.22; 8.60], p = 0.0017), with an I2-value = 0.0% (95%-CI [0.0%; 84.7%]; p-value = 0.71). Eggers' test, on the other hand, found publication bias in anti-MAP antibodies data (intercept = 1.61, 95% CI: 0.45 – 2.77, t = 2.72, p = 0.021), but not in MAP DNA dataset (intercept = -5.57, 95% CI: -20.44 – 9.29, t = -0.74, p = 0.54). The robustness of the meta-analyses was demonstrated by all sensitivity analyses. In addition, there is no evidence of p-hacking observed (right-skewness test (PFull < 0.001, PHalf <0.001; statistical power ≥ 94% (95%-CI: 72.5%-99%)). In conclusion, the synthesis revealed a strong association between MAP and MS, indicating that MAP is a significant environmental agent that may trigger MS. Thus, early screening of MAP in MS cases may assist in the therapeutic approach to its management/treatment. Therefore, future studies should be tailored towards the role of MAP in the severity of MS phenotypes, as well as address global data gaps and low disease surveillance.