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

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.

Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal cancer patients

“…The results point to a continuous activation of monocytes/macrophages in the course of IBD and correspond to other results (Hyun and Mayer 2006;Rogler and Andus 1998). Nevertheless, the causal factors beyond the activation of the cells are incompletely understood, although experiments on animal models provide evidence for the importance of antigens of commensal bacteria in stimulation of the mucosal immune system (Rennick and Fort 2000;Sartor 2004). Mycobacterium avium subspecies paratuberculosis is also currently suggested to determine bacterial signals which induce the pro-inflammatory response in CD (Bull et al 2003;Szkaradkiewicz et al 2007).…”

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

“…No antibiotics were used as prophylaxis or treatment for opportunistic infections in the transplant recovery period, because there is extensive evidence that experimental colitis is attenuated when animals are treated with antibiotics. 26,27 Global leukocyte counts were performed daily in a Neubauer chamber from the fifth day until the sixteenth day after BMC infusion to assess immune reconstitution in transplanted mice.…”

Role of STAT3 in inflammatory bowel disease

“…Dysregulated host/microbial interactions have been postulated to play a crucial role in the development of IBD by inducing uncontrolled activation of acquired immune responses [24,[28][29][30] . Innate immune responses mediated by CECs and phag ocytic cells such as macrophages play a crucial role in the initial defense to maintain the appropriate host/microbial interactions [15,22] .…”