Efficacy Of Probiotics In Inflammatory Bowel Disease Probiotics in Animal Models of IBD

The efficacy of probiotics in attenuating colitis has been demonstrated in experimental animal models (Table 2). These models include the interleukin-10 knockout murine model (81-84), methotrexate induced colitis (85), HLA-B27 transgenic rats (86), and the CD45Rbhi transfer model (87).

The model of IL-10 knockout mice develop colitis when colonized with normal enteric microbiota but remain disease-free if kept in germ-free conditions. In a study of IL-10k/k mice colonization with Lactobacillus plantarum 299v was performed 2 weeks before transferring from a germ-free environment to a specific pathogen-free environment (84). This treatment led to a reduction in disease activity and a significant decrease in mesenteric lymph node IL-12 and IFN-g production. A role for Lactobacillus reuteri in prevention of colitis in IL-10k/k mice was also demonstrated (81). In this study, the oral administration of the prebiotic lactulose (shown to increase the levels of Lactobacillus species) and rectal swabbing with L. reuteri restored Lactobacillus levels to normal in neonatal mice, originally found to have low levels of lactobacilli species. This effect was associated with the attenuation of colitis. In a placebo controlled trial, orally administered Lactobacillus salivarius UCC118 reduced the incidence of colon cancer and the severity of mucosal inflammation in IL-10k/k mice (82). L. salivarius was also shown to modify the gut microbiota in these animals as Clostridium perfringens, enterococci and coliform levels were significantly reduced in the probiotic group. A further trial confirmed the efficacy of L. salivarius UCC118 and demonstrated efficacy for Bifidobacterium infantis 35624 in attenuation of colitis in the IL-10 /k mouse model (83). The amelioration of disease activity in this study was associated with modulation of the gut microbiota as investigated by culture-independent 16S ribosomal RNA targeted PCR-direct gradient gel electrophoresis. In addition, mucosal pro-inflammatory cytokine production was significantly reduced. Indeed, the oral route of administration may not be essential for certain probiotic effects. Reduced inflammatory scores and reduced production of pro-inflammatory cytokines have been observed in IL-10k/k mice which had been injected subcutaneously with L. salivarius UCC118 (73).

Modified Probiotics in Animal Models

Combinations of probiotic treatment with prebiotics or antibiotics have been used to increase the beneficial effect. The combination of the prebiotic inulin, and the probiotic

Table 2 Summary of Probiotic Efficacy in Animal Models of Enterocolitis

Probiotic microorganism

Type of study

Trial outcome

Reference

Lactobacillus reuteri

IL-10k/k mice. N = 4-8

Prebiotic lactulose and

Madsen et al.

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