Microbial-host interactions in inflammatory bowel diseases and experimental colitis.
The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are immunologically mediated with genetic and environmental influences. Genetic factors include defective immunoregulation, mucosal integrity/repair and bacterial killing. Commensal bacteria activate pathogenic bacterial antigen-specific effector T cells that cause chronic inflammation in genetically susceptible hosts but induce protective immune responses in normal subjects. Both host and microbial specificities are important. Some bacterial species are aggressive, some are neutral and others protective, but each species has different effects in various hosts. Molecular techniques demonstrate contraction of certain bacterial populations in IBD, especially clostridial subsets, and expansion of others, including Enterobacteriaceae. The balance of beneficial and detrimental bacterial species determines homeostasis vs. inflammation; this balance can be manipulated by antibiotics, probiotics and prebiotics to treat and prevent relapses of IBD. Adherent/invasive Escherichia coli that adhere to and invade epithelial cells and resist killing by macrophages are increased in ileal CD.


OBJECTIVE
Invasive, translocating, intracellular commensal bacteria induce Th1 and Th17 responses that cause CD in susceptible individuals with genetically determined innate immune defects. UC is caused by bacterial metabolic products that induce epithelial injury by blocking epithelial metabolism or overwhelming the genetically susceptible host's ability to degrade reactive oxygen species.
Sartor
R Balfour
RB
Departments of Medicine, Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA. rbs@med.unc.edu
D000818:Animals; D001419:Bacteria / Q000276:immunology; D018407:Bacterial Physiological Phenomena; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000382:microbiology* / Q000628:therapy; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*