Transición del adolescente con enfermedad inflamatoria intestinal desde la atención pediátrica a la del adulto / Transition to adulthood of adolescents with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a prevalent chronic disorder, often diagnosed during childhood. Studies have suggested that the incidence of IBD in this group of patients is increasing. Children and adolescents with IBD frequently have more extensive and severe disease than adults. Transition is an important concept to ensure optimal health care management of adolescents and young adult patients with chronic physical and medical conditions. During this process there is a change in knowledge, attitudes and behavior towards the disease with a responsibility that gradually shifts from parents to the patient. The success of the transition process depends on the patient, pediatric and adult gastroenterologists. Thus, providers need to understand how to start, maintain and finish this process. When transition process is coordinated, staged and well planned, the adolescent and young adult will acquire the tools needed to successfully self-manage his or her own medical condition. Rather than a universal model of transition, each institution needs to adapt the most efficient model. The aim of this article is to review concepts pertinent to transition management for adolescents and young adults with IBD.

Adherent-invasive Escherichia coli blocks interferon-γ-induced signal transducer and activator of transcription (STAT)-1 in human intestinal epithelial cells.

Adherent-invasive Escherichia coli (AIEC) is a pathogen isolated from the ileum of patients with Crohn disease. IFNγ is a key mediator of immunity, which regulates inflammatory responses to microbial infections. Previously, we showed enterohemorrhagic E. coli prevents STAT1 activation. The aim of this study was to determine whether activation of STAT1 by IFNγ was prevented by AIEC infection, and to define the mechanisms used. Human epithelial cells were infected with three different AIEC strains or other pathogenic and commensal E. coli strains. Following infection, cells were stimulated with IFNγ, and STAT1 activation was monitored by immunoblotting. Our data show that live AIEC with active protein synthesis machinery is able to prevent IFNγ-mediated STAT1 phosphorylation, and that a secreted factor may be involved. We conclude that the suppression of epithelial cell STAT1 signal transduction by AIEC strains isolated from patients with Crohn disease represents a novel mechanism by which the pathogen evades host immune responses to the infection.

Enterohemorrhagic Escherichia coli O157:H7 Shiga toxins inhibit gamma interferon-mediated cellular activation.

Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is a food-borne pathogen that causes significant morbidity and mortality in developing and industrialized nations. EHEC infection of host epithelial cells is capable of inhibiting the gamma interferon (IFN-γ) proinflammatory pathway through the inhibition of Stat-1 phosphorylation, which is important for host defense against microbial pathogens. The aim of this study was to determine the bacterial factors involved in the inhibition of Stat-1 tyrosine phosphorylation. Human HEp-2 and Caco-2 epithelial cells were challenged directly with either EHEC or bacterial culture supernatants and stimulated with IFN-γ, and then the protein extracts were analyzed by immunoblotting. The data showed that IFN-γ-mediated Stat-1 tyrosine phosphorylation was inhibited by EHEC secreted proteins. Using two-dimensional difference gel electrophoresis, EHEC Shiga toxins were identified as candidate inhibitory factors. EHEC Shiga toxin mutants were then generated and complemented in trans, and mutant culture supernatant was supplemented with purified Stx to confirm their ability to subvert IFN-γ-mediated cell activation. We conclude that while other factors are likely involved in the suppression of IFN-γ-mediated Stat-1 tyrosine phosphorylation, E. coli-derived Shiga toxins represent a novel mechanism by which EHEC evades the host immune system.

Adherent-invasive Escherichia coli, strain LF82 disrupts apical junctional complexes in polarized epithelia.

BACKGROUND: Although bacteria are implicated in the pathogenesis of chronic inflammatory bowel diseases (IBD), mechanisms of intestinal injury and immune activation remain unclear. Identification of adherent-invasive Escherichia coli (AIEC) strains in IBD patients offers an opportunity to characterize the pathogenesis of microbial-induced intestinal inflammation in IBD. Previous studies have focused on the invasive phenotype of AIEC and the ability to replicate and survive in phagocytes. However, the precise mechanisms by which these newly identified microbes penetrate the epithelial lining remain to be clarified. Therefore, the aim of this study was to delineate the effects of AIEC, strain LF82 (serotype O83:H1) on model polarized epithelial monolayers as a contributor to intestinal injury in IBD. RESULTS: Infection of T84 and Madin-Darby Canine Kidney-I polarized epithelial cell monolayers with AIEC, strain LF82 led to a reduction in transepithelial electrical resistance and increased macromolecular (10 kilodalton dextran) flux. Basolateral AIEC infection resulted in more severe disruption of the epithelial barrier. Increased permeability was accompanied by a redistribution of the tight junction adaptor protein, zonula occludens-1, demonstrated by confocal microscopy and formation of gaps between cells, as shown by transmission electron microscopy. After 4 h of infection of intestine 407 cells, bacteria replicated in the cell cytoplasm and were enclosed in membrane-bound vesicles positive for the late endosomal marker, LAMP1. CONCLUSION: These findings indicate that AIEC, strain LF82 disrupts the integrity of the polarized epithelial cell barrier. This disruption enables bacteria to penetrate into the epithelium and replicate in the host cell cytoplasm. These findings provide important links between microbes related to IBD, the intestinal epithelial cell barrier and disease pathogenesis.

Unraveling mechanisms of action of probiotics.

Probiotics are defined as living organisms that, when administered in sufficient numbers, are of benefit to the host. Current evidence indicates that varying probiotic strains mediate their effects by a variety of different effects that are dependent on the dosage employed as well as the route and frequency of delivery. Some probiotics act in the lumen of the gut by elaborating antibacterial molecules such as bacteriocins; others enhance the mucosal barrier by increasing the production of innate immune molecules, including goblet cell-derived mucins and trefoil factors and defensins produced by intestinal Paneth cells; and other probiotics mediate their beneficial effects by promoting adaptive immune responses (secretory immune globulin A, regulatory T cells, interleukin-10). Some probiotics have the capacity to activate receptors in the enteric nervous system, which could be used to promote pain relief in the setting of visceral hyperalgesia. Future development of the effective use of probiotics in treating various gastroenterological disorders in human participants should take advantage of this new knowledge. The creation of novel formulations of probiotics could be directed to effectively target certain mechanisms of actions that are altered in specific disease states.