Microbial host interactions in IBD: implications for pathogenesis and therapy.
Crohn's disease (CD), ulcerative colitis (UC), and pouchitis appear to be caused by pathogenic T-cell responses to discrete antigens from the complex luminal microbiota, with susceptibility conferred by genetic polymorphisms that regulate bacterial killing, mucosal barrier function, or immune responses. Environmental triggers initiate or reactivate inflammation and modulate genetic susceptibility. New pathogenesis concepts include defective bacterial killing by innate immune cells in CD, colonization of the ileum in CD with functionally abnormal Escherichia coli that adhere to and invade epithelial cells and resist bacterial killing, and alterations in enteric microbiota composition in CD, UC, and pouchitis detected by molecular probes. The considerable therapeutic potential of manipulating the enteric microbiota in inflammatory bowel disease patients has not been realized, probably due to failure to recognize heterogenic disease mechanisms that require individualized use of antibiotics, probiotics, prebiotics, combination therapies, and genetically engineered bacteria to restore mucosal homeostasis.
Sartor
R Balfour
RB
Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, CB #7032, Room 7309, Medical Biomolecular Research Building, Chapel Hill, NC 27599, USA. rbs@med.unc.edu
Muehlbauer
Marcus
M
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D003093:Colitis, Ulcerative / Q000276:immunology / Q000382:microbiology; D003424:Crohn Disease / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology; D005818:Genetic Engineering; D006706:Homeostasis / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D015212:Inflammatory Bowel Diseases / Q000382:microbiology*; D010587:Phagocytosis / Q000502:physiology; D019936:Probiotics / Q000627:therapeutic use; D012294:Rifamycins / Q000627:therapeutic use; D000078262:Rifaximin; D013601:T-Lymphocytes / Q000276:immunology; D014774:Virulence
D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D012294:Rifamycins; C419843:TLR protein, bacteria; D000078262:Rifaximin