Intestinal microflora as a therapeutic target in inflammatory bowel disease

Mitsuyama, Keiichi; Toyonaga, Atsushi; Sata, Michio

doi:10.1007/bf03326418

Cited by 27 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Particularly IBD is characterized by dysregulation of the immunological response to the intestinal flora. There are many reports suggesting the prevention of IBD with probiotics (Venturi et al 1999;Gionchetti et al 2000;Ishikawa et al 2003) or prebiotics (Mitsuyama et al 2002) in human. In HF-SFB mice with colitis induced by dextran sulphate sodium or gene-knock out, we will be able to investigate the mechanism for the pro/prebiotic effects on IBD diseases in near future.…”

Section: Discussionmentioning

confidence: 99%

Improvement of human faecal flora-associated mouse model for evaluation of the functional foods

et al. 2004

View full text Add to dashboard Cite

Aims: Animal models are required for evaluation of the functional foods such as pro/prebiotics exerting effects through the metabolism of the intestinal microflora. The object of this study was to establish new human floraassociated mice reflecting the environment of the human intestinal tract. Methods and Results: We inoculated a human faecal suspension into segmented filamentous bacteria (SFB) monoassociated mice as a model system. In both human flora (HF) and SFB-associated mouse (HF-SFB mouse), intestinal characteristics such as the composition of intraepithelial lymphocytes, the expression of major histocompatibility complex (MHC) class II molecules and the number of immunoglobulin A-producing cells in the mucosa was closer to those of conventionally reared mice than was case with human flora-associated mice (HF mice) lacking SFB. Several predominant bacterial groups except lactobacilli in human flora were found in faeces of HF-SFB mice. Lactobacilli established small populations in the gut of HF-SFB mice when administered before inoculation with the human flora. Faecal enzymatic activities and organic acid concentration of HF-SFB mice proportionally reflected those of the donor subject. Conclusion: We established a new human flora-associated mouse (HF-SFB mouse), in which intestinal characteristics are normally developed and their major microbial composition reflect the human. Significance and Impact of the Study: HF-SFB mice are a valuable model for studying pro/prebiotic effects on the human intestine.

show abstract

Section: Discussionmentioning

confidence: 99%

Improvement of human faecal flora-associated mouse model for evaluation of the functional foods

et al. 2004

View full text Add to dashboard Cite

show abstract

“…120 Four-week administration of 20 -30 g of germinated barley extracts to patients with mild to moderate ulcerative colitis decreased clinical and endoscopic evidence of inflammation in both a pilot and a small placebo-controlled trial. 121,122 This treatment increased fecal concentrations of Bifidobacterium species and Eubacterium limosum. A longerterm (24 wk) open-label study of 21 patients reached similar conclusions.…”

Section: Human Ibdmentioning

confidence: 98%

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

2004

View full text Add to dashboard Cite

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.

show abstract

“…those with overt bacterial overgrowth) could be a more rationale and effective study. Nonetheless, taken as a whole, these data suggest that in patients with UC, even without gross disease activity, investigation of the long‐term administration of effective probiotics/symbiotics together with standard treatment, should be pursued and the inner mechanisms and clinical relevance further clarified, as recently stressed by Mitsuyama et al at a dedicated symposium 41 .…”

Section: Discussionmentioning

confidence: 92%

Disrupted mucosal barrier in quiescent ulcerative colitis: effect of metronidazole and of a symbiotic preparation in a pilot cross‐over study

Marotta

Naito²,

Tajiri

et al. 2003

Chinese Journal of Digestive Diseases

View full text Add to dashboard Cite

OBJECTIVES: The aims of the present study were to investigate the plasma concentration of endotoxin in patients with inflammatory bowel disease (IBD), the effect of metronidazole (MNZ) and of symbiotics on that concentration, and the relationship to IBD activity. METHODS: The study group comprised 26 patients with quiescent ulcerative colitis (UC), all of whom were on maintenance mesalazine treatment (1200− 2400 mg/day). The control group comprised 15 subjects. Blood samples were taken from all study subjects to measure: routine blood chemistry, endotoxin concentration, lipopolysaccharide binding protein (LBP) and macrophage‐colony stimulating factor (M‐CSF). All the IBD patients were randomly enrolled for a 2‐week oral daily treatment regimen with either MNZ (250 mg t.i.d.) or the symbiotic mixture SCM‐III (Lactobacillus acidophilus, L. helveticus and Bifidobacteria brevis in an ion‐ and vitamin‐enriched medium; 3 mL t.i.d.). Following a 6‐week washout period during which the patients continued their maintenance treatment, the cross‐over study of the new treatments was begun. Blood parameters were checked at entry and 2 weeks after each treatment schedule. RESULTS: The concentration of endotoxin level in the UC patients, as a whole, was comparable with that of the control subjects. However, a separate group of patients with long‐standing disease and pancolitis showed a statistically significant increase in toxin. SCM‐III, but not MNZ, normalized this parameter. There was no statistical change in LBP and plasma endotoxin‐inhibiting capacity in the IBD patients. The M‐CSF concentration was increased in the UC group, particularly in the pancolitis subgroup. SCM‐III, but not MNZ, significantly decreased the M‐CSF concentration in the UC patients, but there was only an insignificant trend toward decrease in the subgroup. There was a significant correlation between M‐CSF and endotoxin in the pancolitis subgroup (r: 0.74, P < 0.05). CONCLUSIONS: Although these preliminary results need to be treated with caution, they suggest the effectiveness of long‐term administration of probiotics/symbiotics in conjunction with standard treatment in patients with UC, even if there is not gross disease activity.

show abstract

Intestinal microflora as a therapeutic target in inflammatory bowel disease

Cited by 27 publications

References 29 publications

Improvement of human faecal flora-associated mouse model for evaluation of the functional foods

Improvement of human faecal flora-associated mouse model for evaluation of the functional foods

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

Disrupted mucosal barrier in quiescent ulcerative colitis: effect of metronidazole and of a symbiotic preparation in a pilot cross‐over study

Contact Info

Product

Resources

About