Probiotics Therapeutic Properties
Lactic acid-producing microbes are the most common components of probiotic therapies and desirable members of the colonic microflora. The microorganisms should be, as stated above, of human origin and survive in the intestine although not for the long term (9, 49). Different strains of probiotic bacteria have very different and specialized functions (49). In their review, Campieri and Gionchetti (49) reported that most of the data on probiotics come from experimental conditions and create scepticism among researchers, because the mechanisms by which probiotic bacterial strains antagonize pathogenic gastrointestinal microorganisms or benefit the host in vivo have not yet been fully defined.
The exogenous administration of Lactobacillus reuteri, either as pure bacterial suspension or as fermented oatmeal soup, prevented the development of acetic acid-induced colitis or methotrexateinduced colitis in rats (49). L. plantarum might even more effectively attenuate the prevention of methotrexate-induced colitis.
It was very recently reported that nonvirulent Salmonella attenuated the synthesis of inflammatory effector molecules in response to diverse inflammatory stimuli in a model of human epithelial cells (50). This antiinflammatory action involved the inhibition of NFKB activation by blocking inhibitor KB-cx ubiquitination and degradation (51). The NFKB signaling system was involved in regulating gene expression in cells such as B-cells (52). NFKB is a heterodimeric transcription factor that acts in both immune and non immune cells (52).
The signal detection by a cell surface receptor complex triggers a biochemical cascade in the cytoplasm, which frequently includes a Toll receptor family member and causes the degradation of a protein bound to the NFKB complex, IKB. The NFKB complex is then allowed to pass from the cytoplasm into the nucleus of the cell and, finally, bind and activate the transcription of one or more genes (52).
Nonpathogenic E. coli strains as probiotics
The proposed mechanism of action for a nonpathogenic strain such as E. coli is that they block the receptors to prevent the adhesion of bacteria. The antagonistic activity against pathogenic and nonpathogenic enterobacteria probably takes place through the production of antimicrobial substances and changes in the pH or chemical composition of the colonic lumen.
Probiotics seem the most promising option in the treatment of ulcerative colitis as they manipulate the normal intestinal flora (53). The possible mechanisms of action have been described by Farrell et al. (53). To test the effects of probiotic treatment, two groups were compared. The first group was given an oral preparation of nonpathogenic E. coli Nissle, two capsules a day and the second group 1.5 I1g mesalazine daily. For this trial a total of 120 patients with inactive ulcerative colitis were included in a 12-week double-blind study to assess the efficacy of probiotics in preventing a relapse of the disease. The results showed no significant differences between the two groups. Consequently, probiotics offer another option for maintenance therapy of ulcerative colitis (54). Another study with ulcerative colitis patients was a double-blind 12-month trial. Two groups were compared one was given an oral E. coli preparation, two capsules twice a day and the other was given mesalazine 2.4 I1g daily. The results suggested that treatment with a nonpathogenic E. coli had an equivalent effect to mesalazine in maintaining remission of ulcerative colitis (55). Although these randomized, controlled trials (54, 55) showed that an enteric-coated capsule containing nonpathogenic E. coli (Nissle 1917) is as effective as mesalazine for maintaining remission in ulcerative colitis, they have been criticized due to the low dose of mesalazine used. According to Faubion et al. (56) this study did have several flaws. The patient group was heterogeneous with regard to severity of illness (mild to severe), and was treated with several different corticosteroid formulations as well as the study medication. Furthermore, the doses of mesalazine used were relatively low and only a very small number of patients remained in remission at the end of the study (57).