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It is clear, from the foregoing discussions, that there is significant evidence, both experimental and clinical, to indicate that certain strains of probiotic organisms can modulate the immune system of the host. The two major impacts that have been demonstrated so far include immunostimulation and immunoregulation. Immunostimulation involves an elevation of immune function(s) to a heightened state of responsiveness, and may provide an important role in conditions where an elevation of immune function is not achievable by conventional means or in boosting responses among individuals with sub-optimal immunity. Experimentally, several strains of Lactobacillus and Bifidobacterium have been shown to boost humoral antibody responses to experimentally administered T-cell-dependent antigens (Portier et al., 1993; Perdigon et al., 1995; Gill et al., 2000). In human studies, Lactobacillus GG has been shown to enhance the humoral immune response to orally administered rotavirus and Salmonella typhi vaccines (Isolauri et al., 1995; Fangac et al., 2000), while B. breve enhances IgA antibody responses to poliomyelitis vaccine (Fukushima et al., 1998), thus providing evidence of the potential use of probiotics as oral adjuvants to boost immune responses at the gut mucosal surface. Future uses of probiotics may be expanded to their use as oral adjuvants to promote immune responses against vaccines that currently can only be administered parenterally - for example, to boost circulating antibody responses to orally administered influenza vaccine (Maassen et al., 2000).

A further role for immune-stimulating probiotics is their use in boosting immune function in individuals with suboptimally functioning immunity. Lactobacillus GG has already been mentioned as an oral immunostimulator to enhance antibody responses in children combating rotavirus infection, and pro-biotics may prove very useful in this context of boosting immunity among malnourished children or infants with poorly developed sensitization. At the other end of the age spectrum, probiotics may prove useful in boosting immunity among elderly subjects. Studies have shown that senescence of the immune system can predispose the elderly to infectious and non-infectious diseases and that a decline in immune function with age can contribute to decreased life expectancy (Roberts-Thomson et al., 1974; Goodwin, 1995). Immuno-senescence is characterized by a suboptimal functioning of the cellular immune system in particular, mainly involving T-cell-mediated responses but also some NK-cell and phagocyte functions (Lesourd and Meaume, 1994; Butcher et al., 2000; Solana and Mariani, 2000). In this respect, it has been demonstrated that

L. rhamnosus (strain HN001) and B. lactis (strain HN019) are both effective at boosting cellular immune function among healthy middle-aged and elderly subjects (Arunachalam et al., 2000; Chiang et al., 2000; Gill and Rutherfurd, 2001; Gill et al., 2001a, b, c; Sheih et al., 2001). Thus, certain probiotic strains may offer benefit to elderly consumers by stimulating the very compartments of the immune system that are adversely affected by ageing.

The immunoregulatory role of probiotics has probably received the greatest degree of attention in experimental research. A large proportion of this work has thus far focused on probiotic LAB, which induce the anti-allergy cytokines IL-12 and IFN-7, for their potential use in preventing atopic responses and combating allergies. Yet there is still only limited clinical evidence that orally delivered probiotics are effective at combating allergic symptoms among at-risk groups (Trapp et al., 1993; Wheeler et al., 1997). In contrast, there is gathering clinical evidence that certain probiotic strains can be used effectively in neonatal and paediatric care to provide the necessary bacterial signals which, in early life, enable the immune system to develop appropriately and to avoid allergic sensitization (Isolauri et al., 2000; Kalliomaki et al., 2001).

Other potential uses of immunoregulatory probiotics (e.g. in controlling inflammatory diseases at the gut surface) have only recently begun to attract research attention (Venturi et al., 1999), partly because the microbial: gut mucosal signalling mechanisms are only beginning to be understood by microbiological researchers (Haller et al., 2000). A recent pilot study (Gupta et al., 2000) showed promising preliminary results for the use of L. rhamnosus GG as a dietary supplement to reduce clinical indices of GI-tract inflammation in children with Crohn's disease. As research starts to define the interactions of the gut microflora and the immune system in the maintenance of health, so it is likely that new avenues for dietary intervention will become the focus of research efforts.

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