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Mapping Crohn’s Disease Pathogenesis with Mycobacterium paratuberculosis: A Hijacking by a Stealth Pathogen

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An Invited Commentary to this article was published on 20 June 2024

Abstract

Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn’s disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne’s disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.

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Acknowledgments

The authors would like to acknowledge Professor John Hermon-Taylor who died October 2022. His work, talent, persistence and determination from the 1970’s to his last days, enabled the present understanding of MAP and the discovery of IS900. He also created multiple treatments for patients with Crohn’s disease and improved their lives immeasurably.

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Correspondence to Gaurav Agrawal.

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GA has no conflict of interest. TJB has filed patents in anti-MAP therapy and JMA has developed and has patents in mycobacterial culture media for CWDM, some of which were used to obtain the photomicrographs which accompany this article.

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Agrawal, G., Borody, T.J. & Aitken, J.M. Mapping Crohn’s Disease Pathogenesis with Mycobacterium paratuberculosis: A Hijacking by a Stealth Pathogen. Dig Dis Sci 69, 2289–2303 (2024). https://doi.org/10.1007/s10620-024-08508-4

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