Probiotics in inflammatory bowel disease: possible mechanisms of action.
OBJECTIVE
Probiotics are live, nonpathogenic bacteria that confer health benefits beyond their nutritional value. In inflammatory bowel disease, where changes in bacterial flora have been demonstrated, there is an increasing interest in modulating the flora with probiotic strains. The beneficial effect of probiotics is demonstrated mainly in pouchitis and ulcerative colitis; however, their mechanisms of action are not well defined. The purpose of this review is to discuss the latest findings related to their mechanism of action.


RESULTS
A decrease in the secretion of pro-inflammatory cytokines, IFN-gamma, TNF-alpha and IL-12, and interference with bacterial adherence to the epithelium has been demonstrated. At the molecular level, an anti-inflammatory effect associated with NF-kappaB inhibition, heat-shock protein induction and proteasome inhibition has been suggested, although NF-kappaB induction has also been demonstrated. Unexpectedly, the beneficial effects described were achieved not only by live bacteria but also by gamma-irradiated nonviable bacteria, bacterial DNA components and probiotic-cultured media.


CONCLUSIONS
Understanding the mechanisms responsible for the beneficial effect of probiotics in inflammatory bowel disease and experimental colitis may help understand the role of bacteria in disease pathogenesis. The findings that live probiotics may not be mandatory to be beneficial, and that therapeutic effects may be obtained by systemic, rather than oral administration could have a major impact on the practical use and manufacturing of probiotics.
Dotan
Iris
I
IBD Service, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel.
Rachmilewitz
Daniel
D
D000818:Animals; D001644:Bifidobacterium / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D007778:Lactobacillus / Q000502:physiology*; D019936:Probiotics / Q000627:therapeutic use*
D016207:Cytokines