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Mapping Crohn's Disease Pathogenesis with Mycobacterium paratuberculosis: A Hijacking by a Stealth Pathogen
Gaurav Agrawal1,2, Thomas J Borody3, John M Aitken4
1Division of Diabetes & Nutritional Sciences, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK. Gaurav.agrawal@kcl.ac.uk.
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.
Insights
Mycobacterium avium ssp. paratuberculosis (MAP) may cause Crohn's disease (CD) through a multi-step process. Improved detection methods are crucial for confirming this infectious link and guiding combination therapies.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Mycobacterium avium ssp. paratuberculosis (MAP) is a suspected cause of Crohn's disease (CD), sharing pathological similarities with Johne's disease (JD) in ruminants.
- The development of CD is thought to involve MAP infection, gut dysbiosis, and dietary factors, necessitating a comprehensive understanding for effective treatment.
Purpose of the Study:
- To review the potential role of MAP in Crohn's disease pathogenesis.
- To explore how MAP's known pathogenesis in cattle and other human mycobacterial infections inform our understanding of CD.
- To discuss the challenges and implications for diagnostic testing of MAP in CD patients.
Main Methods:
- Review of existing literature on MAP, JD, CD, and mycobacterial infections.
- Analysis of pathological and clinical similarities between JD and CD.
- Examination of current diagnostic methodologies for MAP detection in CD.
Main Results:
- Current diagnostic tests (PCR, DNA sequencing, culture) have been inconclusive in establishing a definitive link between MAP and CD.
- Microscopy and histopathology offer insights into in situ mycobacterial activity and disease manifestations like granulomas.
- Understanding MAP's pathogenesis in cattle and other human mycobacterial infections provides a framework for its potential role in CD.
Conclusions:
- Improved and accurate detection methods for MAP are essential to confirm an infectious etiology for CD.
- Isolation, identification, and cultivation of MAP from human gut tissue would strengthen causal relationship evidence.
- Tailoring combination therapies (antibiotics, FMT, diet) to MAP's activity requires robust microbiological evidence of its presence and influence.
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