Multiple studies have demonstrated alterations in the intestinal microbial community(termed the microbiome) in Crohn's disease(CD) and several lines of evidence suggest these changes may have a significant role in...Multiple studies have demonstrated alterations in the intestinal microbial community(termed the microbiome) in Crohn's disease(CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosaassociated adherent, invasive Escherichia coli(E. coli)(AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili(FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold(M)-cells of the follicle-associated epithelium. Resistance to stress genes(htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn's pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.展开更多
基金Supported by Award from the Ministry of Higher Education and Scientific Research/Cultural Attache-London Libyan Embassy,No.UM873-611-23962National Institute for Health Research(NIHR)Biomedical Research Fellowship,No.BRF-2011-025+3 种基金Shire Innovation Fund for Specialist Registrarsfunding from Crohn’s amd Colitis United Kingdom,No.M-08-1/M-13-2Liverpool NIHR-Biomedical Research Centre for Microbial Diseases(01CD1)Support of the European Science Foundation,in the framework of the Research Networking Programme,The European Network for Gastrointestinal Health Research
文摘Multiple studies have demonstrated alterations in the intestinal microbial community(termed the microbiome) in Crohn's disease(CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosaassociated adherent, invasive Escherichia coli(E. coli)(AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili(FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold(M)-cells of the follicle-associated epithelium. Resistance to stress genes(htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn's pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.
