Gastroenterology: The Pathogenic Potential of Mycobacterium paratuberculosis and Emerging Treatment Targets to Address Increasing Resistance

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 4424

Special Issue Editors


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Guest Editor
Guy's and St Thomas' Hospitals NHS Foundation Trust & Kings College London, London SE1 7EH, UK
Interests: Mycobacterium paratuberculosis; Crohn’s disease; IBD; bacteria; infectious diseases; evolution; microbiome; diet
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Special Issue Information

Dear Colleagues,

Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn’s disease for over a century. Despite recent insights pointing to a multi-modal model of disease pathogenesis, how it causes disease has so far eluded scientists. In part, this is due to the fact that the organism is difficult to culture, and detection and animal studies are rare. This Special Issue focuses on how MAP promotes IBD development with increasing evidence of its carriage/invasive potential and hinderances to potential therapeutic targets, with the aim of progressing existing knowledge of the mechanism of inflammation and the ongoing challenges in therapy. Indeed, therapy could be currently said to be treating the effects of the disease (an overactive immune system) but not the cause, due to a lack of consistent resolution and knowlege. The number of patients suffering from Crohn’s is increasing worldwide without a clear reason as to why. Recent insights into the important role of cell-wall-deficient mycobacteria (CWDM) in the life cycle of Mycobacterium species have not contributed to existing treatment options. Mycobacteria are known to adopt different forms in different stages of growth, such as CWDM. Biofilms are a virulence factor in mycobacterial infections, and the involvement of the microbiome in IBD raises the possibility of the availability of nutrients and complex interactions between mycobacterial growth-promoting factors. The complex nature of the path from infection to disease in IBD patients suggests a multi-step pathology if the mycobacterial infection is the root cause. Moreover, each step is susceptibile to disease development and so provides opportunities for a combination of therapies. An improved understanding of MAP and its detection, especially regarding how it affects the gut epithelium in humans as it does in Johne’s Disease, is crucial.

Dr. Gaurav Agrawal
Prof. Dr. Roger Pickup
Guest Editors

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Keywords

  • Mycobacterium paratuberculosis
  • Crohn’s disease
  • IBD
  • bacteria
  • infectious diseases
  • evolution
  • microbiome
  • biofilm
  • antibiotics
  • tuberculosis
  • mycobacteria
  • cell wall deficient forms

Published Papers (2 papers)

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Review

17 pages, 1399 KiB  
Review
Perioperative Considerations for the Surgical Treatment of Crohn’s Disease with Discussion on Surgical Antibiotics Practices and Impact on the Gut Microbiome
by Shelbi Olson, Lindsay Welton and Cyrus Jahansouz
Antibiotics 2024, 13(4), 317; https://doi.org/10.3390/antibiotics13040317 - 30 Mar 2024
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Abstract
Crohn’s disease, a chronic inflammatory process of the gastrointestinal tract defined by flares and periods of remission, is increasing in incidence. Despite advances in multimodal medical therapy, disease progression often necessitates multiple operations with high morbidity. The inability to treat Crohn’s disease successfully [...] Read more.
Crohn’s disease, a chronic inflammatory process of the gastrointestinal tract defined by flares and periods of remission, is increasing in incidence. Despite advances in multimodal medical therapy, disease progression often necessitates multiple operations with high morbidity. The inability to treat Crohn’s disease successfully is likely in part because the etiopathogenesis is not completely understood; however, recent research suggests the gut microbiome plays a critical role. How traditional perioperative management, including bowel preparation and preoperative antibiotics, further changes the microbiome and affects outcomes is not well described, especially in Crohn’s patients, who are unique given their immunosuppression and baseline dysbiosis. This paper aims to outline current knowledge regarding perioperative management of Crohn’s disease, the evolving role of gut dysbiosis, and how the microbiome can guide perioperative considerations with special attention to perioperative antibiotics as well as treatment of Mycobacterium avium subspecies paratuberculosis. In conclusion, dysbiosis is common in Crohn’s patients and may be exacerbated by malnutrition, steroids, narcotic use, diarrhea, and perioperative antibiotics. Dysbiosis is also a major risk factor for anastomotic leak, and special consideration should be given to limiting factors that further perturb the gut microbiota in the perioperative period. Full article
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14 pages, 654 KiB  
Review
Mycobacterium avium ssp. paratuberculosis and Crohn’s Disease—Diagnostic Microbiological Investigations Can Inform New Therapeutic Approaches
by John M. Aitken, Jack E. Aitken and Gaurav Agrawal
Antibiotics 2024, 13(2), 158; https://doi.org/10.3390/antibiotics13020158 - 5 Feb 2024
Viewed by 2945
Abstract
Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne’s disease (JD), which is a chronic infectious gastrointestinal disease of ruminants and is often fatal. In humans, MAP has been associated with Crohn’s disease (CD) for over a century, without conclusive evidence of [...] Read more.
Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne’s disease (JD), which is a chronic infectious gastrointestinal disease of ruminants and is often fatal. In humans, MAP has been associated with Crohn’s disease (CD) for over a century, without conclusive evidence of pathogenicity. Numerous researchers have contributed to the subject, but there is still a need for evidence of the causation of CD by MAP. An infectious aetiology in CD that is attributable to MAP can only be proven by bacteriological investigations. There is an urgency in resolving this question due to the rising global incidence rates of CD. Recent papers have indicated the “therapeutic ceiling” may be close in the development of new biologics. Clinical trial outcomes have demonstrated mild or inconsistent improvements in therapeutic interventions over the last decades when compared with placebo. The necessity to revisit therapeutic options for CD is becoming more urgent and a renewed focus on causation is essential for progress in identifying new treatment options. This manuscript discusses newer interventions, such as vaccination, FMT, dietary remediation and gut microbiome regulation, that will become more relevant as existing therapeutic options expire. Revisiting the MAP theory as a potential infectious cause of CD, rather than the prevailing concept of an “aberrant immune response” will require expanding the current therapeutic programme to include potential new alternatives, and combinations of existing treatments. To advance research on MAP in humans, it is essential for microbiologists and medical scientists to microscopically detect CWDM and to biologically amplify the growth by directed culture. Full article
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