An imbalance of the T cell immune response is observed in inflammatory bowel disease. Intestinal microbes have been linked to the disease and the disease process leads to severe mucosal injury and systemic translocation of bacterial products. Aminosalicylates, corticosteroids and immunomodulators reduce these aggressive activities but are associated with potentially serious adverse events. The aim of this work was to investigate the effects of administration of prebiotics and probiotics that modulate the gut microflora and modulate the immune response, in ameliorating severity of colitis. The prebiotic, high amylose maize resistant starch was used at two different concentrations. A number of Bifidobacterium and Lactobacillus strains were used as probiotics. BALB/c mice were administered the prebiotics and probiotics and intrarectally infused with 2.5 mg trinitrobenzene sulfonic acid (TNBS) in 45% ethanol, thereby generating colitis. Mucosal cytokine responses, colonic microbial profiles and disease activity indices were monitored. The 5% concentration of high amylose maize resistant starch delayed progression of TNBS colitis as evidenced by reduced weight loss, lesser tissue damage, abrogation of the expression and synthesis of IFN-?? and upregulation of IL-4 and IL-10. The 30% concentration of high amylose maize resistant starch exacerbated the inflammatory response with an increase in acetic acid, coliforms and endopores in the colonic contents. Three strains of bifidobacteria and 3 strains of lactobacilli were individually screened for their activity against TNBS colitis. Each strain had a distinctive effect on the course of colon inflammation. Lactobacillus fermentum VRI 003 was selected for further study as it provided most protection. The ratio of immunosuppressive cytokines to pro-inflammatory cytokines was restored closer to the normal T cell cytokine levels. It also reduced the incidence of translocation of enteric bacteria into the spleens. Dosing a minimum daily dose of 6x109 CFU L. fermentum VRI-003 to ulcerative colitis patients in remission and maintained on standard therapy for 6 months prevented the exacerbation of symptoms, including diarrhea and abdominal pain, and improved the patient general well being. It also suppressed production of IFN-?? and sustained IL-10 levels. Moreover, absence of endospores and lower numbers of coliforms were detected in the faeces of UC patients during L. fermentum VRI-003 treatment. In summary, 5% high amylose maize resistant starch and L. fermentum VRI 003 prevented colon inflammation by changing the nature of the T cell immune response and modifying the colonic microflora in the murine model. The clinical evidence supported these findings.
| Identifer | oai:union.ndltd.org:ADTP/258816 |
| Date | January 2005 |
| Creators | Amansec, Sarah Gracielle, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW |
| Publisher | Awarded by:University of New South Wales. School of Biotechnology and Biomolecular Sciences |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Sarah Gracielle Amansec, http://unsworks.unsw.edu.au/copyright |
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