Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics
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
References (136)
- et al.
Manipulation of the bacterial flora in inflammatory bowel disease
Best Pract Res Clin Gastroenterol
(2003) - et al.
Resident bacterial flora and immune system
Dig Liver Dis
(2002) - et al.
Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum
Gastroenterology
(1998) - et al.
Mucosal flora in inflammatory bowel disease
Gastroenterology
(2002) - et al.
Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection
J Biol Chem
(2003) - et al.
CARD15/NOD2 functions as an anti-bacterial factor in human intestinal epithelial cells
Gastroenterology
(2003) - et al.
Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn’s disease
Am J Gastroenterol
(2002) - et al.
Regional and host specificity of colitis in mice monoassociated with different nonpathogenic bacteria
Gastroenterology
(2003) - et al.
Healing of perineal Crohn’s disease with metronidazole
Gastroenterology
(1980) - et al.
A comparative study of metronidazole and sulfasalazine for active Crohn’s disease: the cooperative Crohn’s disease study in Sweden. II. Result
Gastroenterology
(1982)
Combined budesonide and antibiotic therapy for active Crohn’s diseasea randomized controlled trial
Gastroenterology
Controlled trial of metronidazole treatment for prevention of Crohn’s recurrence after ileal resection
Gastroenterology
A controlled trial comparing ciprofloxacin with mesalamine for the treatment of active Crohn’s disease
Am J Gastroenterol
Efficacy and tolerability of rifaximin, a nonabsorbed oral antibiotic, in the treatment of active Crohn’s diseaseresults of an open-label study
Am J Gastroenterol
A meta-analysis of antimycobacterial therapy for Crohn’s disease
Am J Gastroenterol
Treatment of severe Crohn’s disease using antimycobacterial triple therapy—approaching a cure?
Dig Liver Dis
Open clinical trial of rifabutin and clarithromycin therapy in Crohn’s disease
Dig Liver Dis
Metronidazole therapy for perineal Crohn’s diseasea follow-up study
Gastroenterology
Long-term treatment of ulcerative colitis with ciprofloxacin
Gastroenterology
Diagnosis and treatment of pouchitis
Best Pract Res Clin Gastroenterol
Protective effect of metronidazole in experimental ulcerative colitis
Gastroenterology
Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitisa double-blind, placebo-controlled trial
Gastroenterology
Prophylaxis of pouchitis onset with probiotic therapya double-blind placebo controlled trial
Gastroenterology
Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitisa randomised trial
Lancet
Maintenance of remission in ulcerative colitis is equally effective with Escherichia coli Nissle 1917 and with standard mesalamine
Gastroenterology
VSL3 probiotic mixture induces remission in patients with active ulcerative colitis
Gastroenterology
Use of Lactobacillus-GG in paediatric Crohn’s disease
Dig Liver Dis
Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice
Gastroenterology
Probiotic bacteria enhance murine and human intestinal epithelial barrier function
Gastroenterology
Microbial influences in inflammatory bowel diseaserole in pathogenesis and clinical implications
Inflammatory bowel disease
N Engl J Med
Antibiotics in IBD
Gastroenterol Clin North Am
The bacterial flora in inflammatory bowel diseasecurrent insights in pathogenesis and the influence of antibiotics and probiotics
Scand J Gastroenterol Suppl
Probiotics, infection and immunity
Curr Opin Infect Dis
Rationale for probiotic and antibiotic treatment strategies in inflammatory bowel diseases
Dig Dis
Intestinal bacteria and ulcerative colitis
Curr Issues Intest Microbiol
Role of microecology in chronic inflammatory bowel diseases
Eur J Clin Nutr
Natural biota of the human gastrointestinal tract
Role of the faecal stream in the maintenance of Crohn’s colitis
Gut
An immunocytochemical search for infectious agents in Crohn’s disease
Mod Pathol
A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease
Nature
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease
Nature
Crohn’s diseasea defensin deficiency syndrome?
Eur J Gastroenterol Hepatol
Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)
Clin Exp Immunol
Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria
Gut
Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats
J Clin Invest
Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice
Infect Immun
Orocecal transit time and bacterial overgrowth in patients with Crohn’s disease
J Clin Gastroenterol
Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn’s disease
Aliment Pharmacol Ther
Antibiotics in Crohn’s disease
Gut
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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.