Enteral Nutrition and Microflora in Pediatric Crohn's Disease

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.

The colonic microflora is involved in the pathogenesis of Crohn's disease (CD) but less than 30% of the microflora can be cultured. We investigated potential differences in the faecal microflora between patients with colonic CD in remission (n=9), patients with active colonic CD (n=8), and healthy volunteers (n=16) using culture independent techniques. Quantitative dot blot hybridisation with six radiolabelled 16S ribosomal ribonucleic acid (rRNA) targeting oligonucleotide probes was used to measure the proportions of rRNA corresponding to each phylogenetic group. Temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species diversity. Enterobacteria were significantly increased in active and quiescent CD. Probe additivity was significantly lower in patients (65 (11)% and 69 (6)% in active CD and quiescent CD) than in healthy controls (99 (7)%). TTGE profiles varied markedly between active and quiescent CD but were stable in healthy conditions. The biodiversity of the microflora remains high in patients with CD. Enterobacteria were observed significantly more frequently in CD than in health, and more than 30% of the dominant flora belonged to yet undefined phylogenetic groups.

Aphthous lesions recur in the neoterminal ileum within the first few months after curative resection of the distal ileum in patients with Crohn's disease. These lesions do not originate from microscopic disease that is already present at the time of surgery. To investigate the importance of faecal stream in the pathogenesis of recurrent Crohn's lesions, we have studied 5 patients with Crohn's disease who had ileal resection. After curative resection and ileocolonic anastomosis, a diverting terminal ileostomy was constructed 25-35 cm proximal to the anastomosis thereby excluding the neoterminal ileum, the anastomosis, and the colon from intestinal transit. After six months of exclusion, endoscopy of the ileocolon was undertaken and biopsy specimens were taken. Transit was then restored. Six months after reanastomosis further biopsy specimens were taken. These patients were compared with a control group of 75 patients with Crohn's disease who underwent a one-step ileal resection and ileocolonic anastomosis. None of the 5 patients had endoscopic lesions in the neoterminal ileum after six months of exclusion and biopsies did not show inflammatory changes characteristic of Crohn's disease. By contrast, 53 of 75 patients with one-step surgery had endoscopic recurrence in the neoterminal ileum within six months of surgery. All 5 patients had an important recurrence of disease, both endoscopically and histologically, at ileocolonoscopy six months after reanastomosis. Our findings strongly support the view that recurrence of Crohn's disease in the neoterminal ileum after curative ileal resection is dependent on faecal stream.