Targeting enteric bacteria in treatment of inflammatory bowel diseases: why, how, and when.

PURPOSE

This review discusses the role of bacterial adjuvants and antigens in induction and reactivation of chronic intestinal inflammation in susceptible hosts; discusses the results of recent therapeutic trials of antibiotics, probiotics, and prebiotics; and suggests future treatment strategies.

RECENT FINDINGS

Bacterial adjuvants, including peptidoglycan, lipopolysaccharide, and DNA (CpG) bind to membrane-bound toll-like receptors (TLR-2, 4, and 9. respectively) or cytoplasmic (NOD1 and NOD2) receptors (pattern recognition receptors) that activate nuclear factor-kappaB and transcription of many proinflammatory cytokines and adhesion, costimulatory, and major histocompatibility complex class II molecules. Experimental enterocolitis does not occur in a sterile (germ-free) environment and is prevented and treated by broad-spectrum antibiotics. Individual nonpathogenic intestinal bacterial species selectively induce experimental colitis, with host specificity. Crohn disease and ulcerative colitis patients exhibit pathogenic immune responses (loss of immunologic tolerance) to multiple normal enteric bacterial species and serologic responses to Mycobacterium paratuberculosis. Metronidazole and ciprofloxacin selectively treat colonic Crohn disease, but not ulcerative colitis or ileal Crohn disease, and may prevent recurrence of postoperative Crohn disease. Certain probiotic species decrease relapse of ulcerative colitis and chronic pouchitis and delay onset of pouchitis.

SUMMARY

Normal, nonpathogenic enteric bacteria induce and perpetuate chronic intestinal inflammation in genetically susceptible hosts with defective immunoregulation, bacterial clearance, or mucosal barrier function. Altering the composition and decreasing mucosal adherence/invasion of commensal bacteria with antibiotics, probiotics, and prebiotics can potentially prevent and treat Crohn disease, pouchitis, and possibly ulcerative colitis, but optimal treatments have not yet been identified.