Pathogenesis of Crohn’s disease: Bug or no bug

Bosca-Watts, Marta Maia; Tosca, Joan; Antón, Rosario; Mora, María; Mínguez, Miguel; Mora, Francisco

doi:10.4291/wjgp.v6.i1.1

Cited by 35 publications

(28 citation statements)

References 102 publications

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“…Proposed risk factors for CDI in this patient population include altered nutritional and immunological states, repeated hospitalization, genetic predisposition, and the frequent and recurrent use of immunomodulating drugs. 39 One important risk factor for CDI that our results support is disease extent and phenotype. In previous studies that have reported higher rates of CDI than ours, up to 91% of patients with IBD who developed CDI (including a majority of whom had CD) had colonic disease involvement.…”

Section: Discussionsupporting

confidence: 61%

Clostridium difficile Infection

Roy

Lichtiger

2016

Inflammatory Bowel Diseases

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Background Prolonged antibiotic use is limited by several adverse effects, one of which is Clostridium difficile infection (CDI). The aim of this study was to determine the incidence of CDI in patients receiving chronic antibiotic treatment for Crohn’s disease (CD). Methods We conducted a retrospective review of 100 patients with CD for which ≥6 months of outpatient antibiotic therapy was prescribed. Data were collected regarding demographics, CD phenotype, treatment history, and CDI. The incidence of CDI in our patient population was calculated and compared with historical controls. Results 100 patients were studied—60% of men, mean age 23.9 years at CD diagnosis. Eighty-two percent had disease involving the ileum, and 33% had disease involving the colon. The mean duration of antibiotic therapy was 39.6 months (range, 6–217 months). The most commonly prescribed classes of antibiotics were fluoroquinolones (84%), penicillins (57%), and cephalosporins (32%). Forty-nine percent of patients were treated with concomitant thiopurines, 45% with budesonide, and 41% with biologics. The overall incidence of CDI was 2%. This incidence of CDI was lower than previously reported for non-CD patients receiving chronic antibiotics for continuous-flow left ventricular assist device infections (12.5%) and orthopedic prosthesis infections (22.2%). Conclusions The incidence of CDI is rare in patients receiving chronic antibiotic treatment for CD, and it seems significantly lower than for non-CD populations reported in the literature.

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Section: Discussionsupporting

confidence: 61%

Clostridium difficile Infection

Roy

Lichtiger

2016

Inflammatory Bowel Diseases

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“…Similarly, participation of viruses (e.g. measles virus, mumps virus, cytomegalovirus, Epstein-Barr virus) in the initiation or exacerbation of IBD in human patients is currently under discussion [84,85]. Our data provide evidence that extraintestinal infection can enhance enteric disease.…”

Section: Discussionmentioning

confidence: 61%

Viral Infection of the Central Nervous System Exacerbates Interleukin-10 Receptor Deficiency-Mediated Colitis in SJL Mice

Uhde¹,

Herder²,

Khan

et al. 2016

PLoS ONE

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Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS). The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders. In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease. The findings demonstrate that (i) Ab-mediated IL-10 neutralization leads to progressive colitis with a reduction in Foxp3+ regulatory T cells and increased numbers of CD8+CD44+ memory T cells as well as activated CD4+CD69+ and CD8+CD69+ T cells in uninfected mice. (ii) Concurrent acute TMEV-infection worsened enteric disease-mediated by IL-10R neutralization. Virus-triggered effects were associated with an enhanced activation of CD4+ T helper cells and CD8+ cytotoxic T lymphocytes and augmented cytokine expression. By contrast, (iii) IL-10R neutralization during chronic TMEV-infection was not associated with enhanced peripheral immunopathology but an increased CD3+ T cell influx in the spinal cord. IL-10R neutralization causes a breakdown in peripheral immune tolerance in genetically predisposed mice, which leads to immune-mediated colitis, resembling inflammatory bowel disease. Hyperactive immune state following IL-10R blockade is enhanced by central nervous system-restricted viral infection in a disease phase-dependent manner.

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“…3,4 Translocation has long been observed to occur in patients with severe illness, particularly for extensive burns, pancreatitis, trauma and sepsis. 6 Previous culture-based studies have demonstrated bacterial translocation to be more common in those with IBD: 5-24% of controls, compared with up to 33-48% of patients with IBD, have had organisms isolated from mesenteric lymph nodes. 5 It has been hypothesised for decades that microorganisms are involved in the aetiology of inflammatory bowel diseases (IBD; Crohn disease (CD) and ulcerative colitis (UC)).…”

Section: Introductionmentioning

confidence: 99%

“…5 It has been hypothesised for decades that microorganisms are involved in the aetiology of inflammatory bowel diseases (IBD; Crohn disease (CD) and ulcerative colitis (UC)). 6 Previous culture-based studies have demonstrated bacterial translocation to be more common in those with IBD: 5-24% of controls, compared with up to 33-48% of patients with IBD, have had organisms isolated from mesenteric lymph nodes. 3,4,[7][8][9] The most common organism isolated from mesenteric lymph nodes is Escherichia coli.…”

Section: Introductionmentioning

confidence: 99%