Evidence for the involvement of infectious agents in the pathogenesis of Crohn’s disease

Hertogh, Gert De; Aerssens, Jeroen; Geboes, Karen; Geboes, Karel

doi:10.3748/wjg.14.845

Cited by 76 publications

(50 citation statements)

References 120 publications

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“…Mycobacterium avium subsp paratuberculosis Helicobacter spp, non-jejuni/coli campylobacter and Escherichia coli as well as viruses including Epstein-Barr virus, cytomegalovirus, paramyxoviruses and others [166,167]. However, to date any pathogenic organism has proven to be a causative agent or even correlate to IBD severity.…”

Section: Many Pathogenic Organisms Have Been Investigated As Causing mentioning

confidence: 99%

Microbial Neuro-Immune Interactions and the Pathophysiology of IBD

Aguilera¹,

Melgar²

2016

New Insights Into Inflammatory Bowel Disease

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Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a group of debilitating disorders affecting patient's quality of life and with unknown aetiology. The collected evidence indicates that individuals can develop IBD as a result of genetic susceptibility, a dysregulated immune response and the influence of certain environmental factors. Common symptomatology includes abdominal pain, fever and bowel diarrhoea with blood and/or mucus excretion. The location and extent of disease differ between UC and CD, affecting the mucosal layer in the colon in UC patients, whereas in CD patients, a transmural inflammation is found anywhere in the gastrointestinal tract. Factors associated with IBD pathophysiology include alterations in immune responses, characterized by an atypically T helper (Th)-2 profile in UC, and a Th1/Th17 profile in CD, modifications in epithelial barrier function and alterations in the commensal microbiota composition with blooming of specific pathobionts, for example, adherent-invasive Escherichia coli (AIEC), and with diet. Recent research has uncovered that inflammation, per se, can activate the enteric nervous system inducing neurogenic inflammation and increasing visceral sensitivity, leading to pain. Similarly, alterations in the commensal microbiota composition/ligands have also led to modifications in intestinal nociceptive markers and in visceral pain. In this chapter, we aim to review the mechanisms implicated in microbial neuroimmune axis and its potential contribution to IBD pathophysiology and symptomatology. We focus on the findings identified in animal models and in IBD patients and on the prospective translation of targeting the microbial neuro-immune axis as future therapeutic treatment for intestinal inflammatory conditions.

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Section: Many Pathogenic Organisms Have Been Investigated As Causing mentioning

confidence: 99%

Microbial Neuro-Immune Interactions and the Pathophysiology of IBD

Aguilera¹,

Melgar²

2016

New Insights Into Inflammatory Bowel Disease

View full text Add to dashboard Cite

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“…A second hypothesis is based on an increased permeability of intestinal mucosa which can cause translocation of bacteria and their metabolites from the gastrointestinal tract to mesenteric lymph nodes and other internal organs (De Hertogh et al, 2008). Occurrence of such bacterial translocation in patients with CD after surgery has been documented and has caused systemic inflammatory septic response.…”

mentioning

confidence: 99%

“…paratuberculosis (MAP) could be the causative agent of CD, and has been supported by a considerable body of evidence. Investigators were able to isolate MAP from the inflamed tissue and peripheral blood of CD patients, detect anti-MAP antibodies and also prove its presence using molecular analysis (De Hertogh et al, 2008;Macfarlane et al, 2009). However, this was not enough to prove MAP as causative agent of CD, especially since treatment with drugs against MAP had no effect on the improvement of CD.…”

mentioning

confidence: 99%

“…Several other bacteria have also been associated with CD pathogenesis. These include Listeria monocytogenes, Pseudomonas maltophilia, M. kansasii, Bacteroides fragilis and adherent invasive E. coli (AIEC) (De Hertogh et al, 2008;Macfarlane et al, 2009). The latter is a specific pathovar that has been shown to colonize intestinal mucosa of 36.4% of patients with ileal CD.…”

mentioning

confidence: 99%

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Manipulation of Intestinal Flora as a Way to Treat Crohn's Disease: The Role of Probiotics, Prebiotics and Antibiotics

Zadravec¹,

Štrukelj²,

Berlec³

2012

Crohn's Disease

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“…Failure of mucosal healing with subsequent bacterial translocation may contribute to disease pathogenesis (11,48,72). Mucosal healing is a complex process that requires epithelial sheet migration (restitution) from the wound margins and sometimes also epithelial proliferation (60).…”

mentioning

confidence: 99%

ILK mediates the effects of strain on intestinal epithelial wound closure

Yuan

Sanders

Basson

2011

American Journal of Physiology-Cell Physiology

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The intestinal epithelium is subjected to repetitive deformation during normal gut function by peristalsis and villous motility. Such repetitive strain promotes intestinal epithelial migration across fibronectin in vitro, but signaling mediators for this are poorly understood. We hypothesized that integrin-linked kinase (ILK) mediates strain-stimulated migration in intestinal epithelial cells cultured on fibronectin. ILK kinase activity increased rapidly 5 min after strain induction in both Caco-2 and intestinal epithelial cell-6 (IEC-6) cells. Wound closure in response to strain was reduced in ILK small interfering RNA (siRNA)-transfected Caco-2 cell monolayers when compared with control siRNA-transfected Caco-2 cells. Pharmacological blockade of phosphatidylinositol-3 kinase (PI3K) or Src or reducing Src by siRNA prevented strain activation of ILK. ILK coimmunoprecipitated with focal adhesion kinase (FAK), and this association was decreased by mutation of FAK Tyr925 but not FAK Tyr397. Strain induction of FAK Tyr925 phosphorylation but not FAK Tyr397 or FAK Tyr576 phosphorylation was blocked in ILK siRNA-transfected cells. ILK-Src association was stimulated by strain and was blocked by the Src inhibitor PP2. Finally, ILK reduction by siRNA inhibited strain-induced phosphorylation of myosin light chain and Akt. These results suggest a strain-dependent signaling pathway in which ILK association with FAK and Src mediates the subsequent downstream strain-induced motogenic response and suggest that ILK induction by repetitive deformation may contribute to recovery from mucosal injury and restoration of the mucosal barrier in patients with prolonged ileus. ILK may therefore be an important target for intervention to maintain the mucosa in such patients.

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Evidence for the involvement of infectious agents in the pathogenesis of Crohn’s disease

Cited by 76 publications

References 120 publications

Microbial Neuro-Immune Interactions and the Pathophysiology of IBD

Microbial Neuro-Immune Interactions and the Pathophysiology of IBD

Manipulation of Intestinal Flora as a Way to Treat Crohn's Disease: The Role of Probiotics, Prebiotics and Antibiotics

ILK mediates the effects of strain on intestinal epithelial wound closure

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