Gastroenterology

Gastroenterology

Volume 126, Issue 6, May 2004, Pages 1620-1633
Gastroenterology

Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics

https://doi.org/10.1053/j.gastro.2004.03.024Get rights and content

Abstract

Crohn’s disease, ulcerative colitis, and pouchitis are caused by overly aggressive immune responses to a subset of commensal (nonpathogenic) enteric bacteria in genetically predisposed individuals. Clinical and experimental studies suggest that the relative balance of aggressive and protective bacterial species is altered in these disorders. Antibiotics can selectively decrease tissue invasion and eliminate aggressive bacterial species or globally decrease luminal and mucosal bacterial concentrations, depending on their spectrum of activity. Alternatively, administration of beneficial bacterial species (probiotics), poorly absorbed dietary oligosaccharides (prebiotics), or combined probiotics and prebiotics (synbiotics) can restore a predominance of beneficial Lactobacillus and Bifidobacterium species. Current clinical trials do not fulfill evidence-based criteria for using these agents in inflammatory bowel diseases (IBD), but multiple nonrigorous studies and widespread clinical experience suggest that metronidazole and/or ciprofloxacin can treat Crohn’s colitis and ileocolitis (but not isolated ileal disease), perianal fistulae and pouchitis, whereas selected probiotic preparations prevent relapse of quiescent ulcerative colitis and relapsing pouchitis. These physiologic approaches offer considerable promise for treating IBD, but must be supported by rigorous controlled therapeutic trials that consider clinical disease before their widespread clinical acceptance. These agents likely will become an integral component of treating IBD in combination with traditional anti-inflammatory and immunosuppressive agents.

Section snippets

Rationale for treatment

There is considerable indirect evidence that components of the complex microecology of the distal ileum and colon contribute to the pathogenesis of Crohn’s disease, ulcerative colitis, and pouchitis (Table 1). 1, 8, 9, 10 Luminal bacterial concentrations reach 107 to 108 organisms/g luminal contents in the terminal ileum, 1011/g in the colon, and 1010–11 in ileal pouches.11 These areas of highest anaerobic bacterial populations are involved preferentially in clinical IBD. Moreover, Crohn’s

Antibiotics

Antibiotics are widely recognized to have an essential role in treating the septic complications of IBD, including the intra-abdominal and perianal abscesses and fistulae of Crohn’s disease, as well as superinfection with pathogens and postoperative wound infection (Table 3). Most clinicians also use broad-spectrum antibiotics as adjuvant treatment of fulminant colitis and toxic megacolon to decrease bacterial translocation. Small bowel bacterial overgrowth is more common than usually

Probiotics

Probiotics are viable microorganisms with beneficial physiologic or therapeutic activities. Originally derived from cultured foods, especially milk products, these protective bacteria and yeast include the lactic acid bacilli, Lactobacillus and Bifidobacterium, a nonpathogenic E. coli strain (E. coli Nissle 1917), Saccharomyces boulardii, Clostridium butyricum, and Streptococcus salivarius subspecies thermophiles. More recently, genetically engineered bacteria that secrete immunosuppressive

Prebiotics

Prebiotics are dietary substances, usually nondigested carbohydrates, that stimulate the growth and metabolism of protective commensal enteric bacteria.116, 117 Lactosucrose, fructo-oligosaccharides, inulin, bran, psyllium, and germinated barley extracts foster the growth of Lactobacillus and Bifidobacterium species and stimulate production of short chain fatty acids, especially butyrate.118, 119 Thus, these prebiotic food additives have the potential to restore the deranged balance of

Conclusions and future directions

Although the rationale for therapeutic manipulation of the luminal microbiota in IBD is uncontested, current data for therapeutic efficacy do not withstand rigorous scrutiny or fulfill current evidence-based standards for using antibiotics, probiotics, and prebiotics in the treatment of IBD. Clinical trials consistently have been underpowered to show equivalency or superiority, many have design flaws that preclude definitive results, or use outcomes, such as mean CDAI, that do not conform with

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    Dr. Sartor has received research support and is a consultant for VSL 3 Pharmaceuticals, and has received honoraria for speaking at symposia and creating a videotape and monograph sponsored by Salix Pharmaceuticals.

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