No Effect of Oral Treatment With an Intestinal Bacterial Strain, Lactobacillus Rhamnosus (ATCC 53103), on Birch Pollen Allergy—A Placebo-Controlled Double Blind Study

T. Helin, S. Haahtela, and Haahtela T. Allergy 2002;57:243–246. Summary: The authors conducted a double-blind placebo-controlled study, in which respiratory and eye symptoms and use of medications in 2 groups of 18 children were compared. Open oral challenge tests with a slice of apple were performed three times: before, during, and after the birch-pollen season. The children in the test-group used Lactobacillus rhamnosus (ATCC 53103) (previously called Lactobacillus casei GG) for 5.5 months: 2.5 months before the pollen season, 1 month during the season (May), and 2 months after. The treatment did not alleviate the symptoms of the patients or reduce the use of medication during the birch-pollen season or the subsequent two months. The treatment did not significantly affect the symptoms caused by apple in the oral challenge tests. Discussion: The dramatic increase in allergic diseases has made the prevention of such diseases a public health priority. Up to now, research has focused on different approaches such as allergen-specific avoidance of potentially harmful food and of respiratory allergens, or active immunoprophylaxis, or the use of probiotic strains. The concept of prevention based on an allergen-nonspecific approach, as is the case with probiotic bacteria, arose the link between allergy and hygiene, because of the suggestion that exposure to certain infections can prevent IgE sensitization to allergens and inflammation triggered by allergen-IgE interactions (1–4). Properly conditioned by microbial agents typical of a traditional life style, the innate immune system would progressively “teach” the adaptive immune system to interact safely with nonmicrobial antigens that possess allergenic properties (“immunoeducation”)(5). The difference in intestinal microflora development between breastfed and formula-fed infants, and the related difference in stimulation and development of the immune response, is hypothesized to contribute substantially to the reduced incidence of infectious diseases such as otitis media, infectious gastroenteritis, but also the reduced incidence of asthma and eczema in breastfed infants compared to formula fed infants. Therefore, the induction of a breastfed-like microflora in formula-fed infants (thus, an increase in lactobacilli and bifidobacteria, and a decrease of bacteroides) may induce the previously mentioned benefits of mother's milk in formula-fed babies. Consequently, IgE sensitization might be prevented by the administration of appropriate microbes or their substracts. However, a scientific approach to the use of microbes in the prevention of IgE sensitization requires profound knowledge of how the newborn's immune response to allergens matures during exposure to an extremely complex microbial world. Majamaa et al. were the first to suggest that Lactobacillus rhamnose casei GG was of benefit in the treatment of atopic eczema (6). However, the results were only partially favorable, and the score evaluating the severity of the eczema was even slightly higher in the treated group than in the control group one month after the end of treatment (6). The same group recently tested the hypothesis that the same microorganisms may be useful in preventing allergic diseases if administered at birth and to pregnant women (7). A crucial point is that comparative data on colonization by Lactobacilli in “treated” or control infants were not given in any of both studies (6,7). Treated and control infants have similar total and specific IgE levels and skin test responses, so the reduced rate of atopic dermatitis among treated infants cannot be explained on the basis of the TH1/TH2 development. The effect of yogurt, inactivated yogurt, and/or no yogurt administered during one year to adults was tested, and it was concluded that yogurt decreased the incidence of nasal allergies and IgE was lower in the yogurt-consuming group (8). However, yogurt with or without Lactobacilli given for one month did not change spirometric functions in adults with moderate asthma (9). Now, Helin et al. did treat teenagers and adults with Lactobacillus rhamnose casei GG examining whether or not treatment did improve symptoms and decreased medication use (10). The probiotic strain could not prevent sensitization to birch pollen and apple food, and no beneficial clinical effect was recorded in the treated patients (10). The least that can be concluded from the few published trials is that data are conflicting and not convincing. None of these trials with probiotic strains provided changes in intestinal microflora from baseline values in treated patients compared to controls. Recently, an absence in increase of “health promoting” was even reported (11). Thus, the evidence supporting the use of probiotic strains in the prevention of allergic disease comes from trials with methodological weaknesses. Also, the long-term effects or safety of probiotic strains given to a naive immune system should be carefully evaluated. Therefore, the concept of using prebiotics in infant formula, stimulating the development of a gastrointestinal flora that is dominated by lactobacilli and bifidobacteria, might be preferable. However, the effect of prebiotics in infant formula in the prevention of allergic diseases has not been reported up to now. Lactic acid bacteria have been shown to enhance the production of interferon type I and II, to reduce the allergen-stimulated production of interleukin-4 and -5, and to induce pro-interferon monokines interleukin-12 and -18, and to stimulate cytokine secretion (12,13). However, it is possible that these properties are strain-dependent or even strain-determined. It may still take many years before the interesting data from basic research can be translated in convincing clinical data. Yvan Vandenplas Academisch Ziekenhuis Vrije Universiteit Brussel Brussels, Belgium

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