Probiotics and the control of immune dysfunctions

The immune system plays an essential role in the regulation of inflammatory-type diseases, and consequently a dysfunction of the immune system can lead to exacerbation of disease. Due to their potential for immune regulation, it has been suggested that probiotics offer potential for the alleviation of several immuno-inflammatory diseases. Perhaps most attention has been given to the ability of probiotics to regulate allergic/atopic responses. In animal studies, L. casei Shirota has been shown to reduce cutaneous anaphylaxis in allergen-sensitized mice following dermal challenge (Yasui et al., 1999a). Both L. casei Shirota and L. plantarum L-137 have been shown to exhibit anti-allergy properties in mice, reportedly due to their ability to induce high-level systemic expression of IL-12 (Murosaki et al., 1998; Kato et al., 1999), which can down-regulate allergic responses. Indeed, some strains of lactobacilli have been shown to elevate systemic levels of IL-12 following oral delivery (Murosaki et al., 1999; Tejada-Simon et al., 1999a), suggesting that this is a major mechanism by which probiotics effect anti-allergy-type immunoregulation.

In human studies of allergic disease, there is longitudinal evidence that consumption of probiotic-supplemented yoghurt over a period of 1 year can lower the circulating levels of IgE and reduce nasal allergies in elderly subjects (Halpern et al., 1991; Trapp et al., 1993; Table 13.2). Wheeler et al. (1997) have shown that shorter-term consumption of probiotics (i.e. 1 month) by adult allergy sufferers can generate a trend towards reduced peripheral blood eosinophil counts and increased IFN-7-secreting activity of lymphocytes, suggesting that probiotic-induced anti-allergy immune regulation may be effective in humans also. A report by Pelto et al. (1998) demonstrated an alternative mechanism for the ability of L. rhamnosus GG to limit hypersensitivity responses in subjects with cows'-milk allergy, namely, that the probiotic can prevent the up-regulation of pro-inflammatory receptors on leucocytes (a response that normally precedes GI tract inflammation in milk-sensitive subjects). Other potential mechanisms by which probiotics might limit food-hyper-sensitivity responses include their ability to stabilize the gut intestinal barrier against macromolecular sensitization (Majamaa and Isolauri, 1997) and/or the enzymatic hydrolysis of potentially allergenic macromolecules (Rokka et al., 1997). In the latter case, an additional mechanism may be the generation of immunoregulatory peptides from milk substrates by the enzymatic action of probiotics, since Sutas et al. (1996a, b) have shown that milk or casein hydro-lysed with L. rhamnosus GG invokes lower levels of pro-allergy immune responses in antigen-stimulated peripheral blood lymphocytes from milk-sensitive subjects than do intact macromolecules.

In addition to anti-allergy immunoregulation, several studies have suggested that probiotics could be used to combat inflammatory-type diseases. There is some evidence that dietary consumption of immunoregulating LAB might assist in combating autoimmune diseases, including juvenile chronic arthritis (Malin et al., 1996), although the potential mechanism for this is uncertain. A recent report has shown that a diet rich in lactobacilli could decrease subjective symptoms of arthritis among rheumatoid patients, although whether this effect was a result of anti-inflammatory immune regulation is uncertain (Nenonen et al., 1998). The potential use of probiotics to augment the routine immune signalling events of the gut microflora, as a means of restoring vital anti-inflammatory immunoregulatory control mechanisms, has recently gained a great deal of attention as a promising means of combating inflammatory bowel disease (Gionchetti et al., 2000). However, definitive proof for the effectiveness of this mechanism remains to be obtained.

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