Resolution of Crohn’s (Johne’s) disease with antibiotics: what are the next steps?

Davis, William C.; Kuenstner, J. Todd; Singh, Shoor Vir

doi:10.1080/17474124.2017.1300529

Cited by 26 publications

(22 citation statements)

References 33 publications

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“…An association between Mycobacterium avium subsp. paratuberculosis (MAP) and CD has been proposed as early as 1913, given striking clinical and histological similarities to inflammatory bowel disease of ruminants; "Johne's disease", as well as ileo-caecal tuberculosis in humans [5]. Both caused from Mycobacteria, with the former being MAP.…”

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confidence: 99%

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

et al. 2020

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Background: Crohn's disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology-Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission.Results: Ten patients were identified to have achieved prolonged remission for 3-23 years (median 8.5 years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36 months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection. Conclusions:Prolonged remission has been achieved for 3-23 years with individualised treatments, with the majority using AMAT ± infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and the dysbiosis of the gut flora, to enable higher rates of prolonged remission.

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confidence: 99%

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

et al. 2020

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“…This case series makes a strong case for urgent randomized control trials (RCTs) to investigate this effect further and whether AMAT should be used as first-line therapy for CD to achieve remission. Remarkable similarities have long been observed between the clinical features and gross pathology of CD and Johne's disease in ruminants, caused by MAP [6]. Since these initial observations, a wealth of data from epidemiological [23][24][25], genetic [26][27][28], experimental human and animal studies [29], clinical trials [12,17,30] and meta-analyses [31,32] have converged to establish a potential pathogenic role for MAP in CD.…”

Section: Discussionmentioning

confidence: 99%

“…Antibiotic therapies have long been used for the treatment of CD [6] and aim to target potential pathogenic agents which have been associated with CD and the imbalance in the gut microbiome commonly seen in patients with CD [7]. One candidate pathogen is Mycobacterium avium subspecies paratuberculosis (MAP), which is the causative organism of a near-identical inflammatory bowel disease in ruminants and primates, termed "Johne's disease" [6]. It belongs to the Mycobacterium avium complex (MAC) group, one of many non-tuberculous mycobacteria (NTM), which are distinct from the other mycobacteria group named the Mycobacterium tuberculosis complex (MTBC), of which some cause pulmonary tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

Targeted Combination Antibiotic Therapy Induces Remission in Treatment-Naïve Crohn’s Disease: A Case Series

et al. 2020

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Prospective trials of anti-mycobacterial antibiotic therapy (AMAT) have proven efficacious in Crohn’s disease (CD) but use as first-line treatment in CD has not been evaluated. This paper reports the outcomes of patients with CD treated with first-line AMAT. This paper consists of a case series of treatment-naïve CD patients who received AMAT as first-line treatment between 2007 and 2014 at a single center. AMAT treatment consisted of rifabutin, clofazimine and clarithromycin, plus either ciprofloxacin, metronidazole or ethambutol. Symptoms, inflammatory blood markers, colonoscopy and histology results, in addition to, the Crohn’s Disease Activity Index (CDAI) were tabulated from patients’ clinical records, and descriptive statistics were conducted. A Wilcoxon signed-rank test assessed the difference in CDAI scores before and while on AMAT. The statistical significance was set at 5%. Clinical remission (CDAI < 150) with rapid improvement in clinical symptoms and inflammatory markers was seen in all eight patients receiving AMAT as sole therapy by 6 weeks. In all eight patients, the median CDAI score decreased significantly, from 289 prior to treatment to 62 at the 12-month follow-up (p < 0.001). Follow-up colonoscopies showed healing of CD ulcers, no visible mucosal inflammation, restoration of normal vascular patterns and complete mucosal healing on histology samples. AMAT as first-line therapy demonstrated a rapid improvement of Crohn’s disease (not previously seen when used as second-line therapy).

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“…MAP causes a fatal infectious enteritis in ruminant animals called paratuberculosis or Johne's disease. Johne's disease of ruminants and Crohn's disease of humans are increasingly regarded as the same disease: paratuberculosis [40][41][42][43]. Meta-analyses have shown that a majority of studies associating MAP with Crohn's demonstrate MAP infection in Crohn's patients [44,45].…”

Section: Mycobacterium Avium Ss Paratuberculosis-mapmentioning

confidence: 99%

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

Dow

2020

Microorganisms

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Bacille Calmette–Guerin (BCG) vaccination is widely practiced around the world to protect against the mycobacterial infection tuberculosis. BCG is also effective against the pathogenic mycobacteria that cause leprosy and Buruli’s ulcer. BCG is part of the standard of care for bladder cancer where, when given as an intravesicular irrigant, BCG acts as an immunomodulating agent and lessens the risk of recurrence. Mycobacterium avium ss. paratuberculosis (MAP) causes a fatal enteritis of ruminant animals and is the putative cause of Crohn’s disease of humans. MAP has been associated with an increasingly long list of inflammatory/autoimmune diseases: Crohn's, sarcoidosis, Blau syndrome, Hashimoto’s thyroiditis, autoimmune diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis, lupus and Parkinson’s disease. Epidemiologic evidence points to BCG providing a “heterologous” protective effect on assorted autoimmune diseases; studies using BCG vaccination for T1D and MS have shown benefit in these diseases. This article proposes that the positive response to BCG in T1D and MS is due to a mitigating action of BCG upon MAP. Other autoimmune diseases, having a concomitant genetic risk for mycobacterial infection as well as cross-reacting antibodies against mycobacterial heat shock protein 65 (HSP65), could reasonably be considered to respond to BCG vaccination. The rare autoimmune disease, relapsing polychondritis, is one such disease and is offered as an example. Recent studies suggesting a protective role for BCG in Alzheimer’s disease are also explored. BCG-induced energy shift from oxidative phosphorylation to aerobic glycolysis provides the immunomodulating boost to the immune response and also mitigates mycobacterial infection—this cellular mechanism unifies the impact of BCG on the disparate diseases of this article.

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Resolution of Crohn’s (Johne’s) disease with antibiotics: what are the next steps?

Cited by 26 publications

References 33 publications

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

Targeted Combination Antibiotic Therapy Induces Remission in Treatment-Naïve Crohn’s Disease: A Case Series

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

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