Jun Kim Ph.D.

Worldwide sensitization rates to common allergens among school children are approaching 40%-50%[1]. The prevalence of disease such as allergic rhinitis, asthma, and atopic dermatitis has been increasing especially in the developed world. For example from 1980 to 1994 the prevalence of asthma increased by 75%, while in the developing world, the lower prevalence of allergic disease has not changed significantly during the same period[2]. The disorders have genetic basis and are heritable, but the rapid increase suggest that there are external factors from the environment. The hygiene hypothesis posits that increased human longevity and allergy prevalence are consequences of lower rate of infections during childhood. Although mechanisms remain unclear, the hygiene hypothesis is generally considered strong.

The association between the gut microbiota and allergy has been focused in multiple studies[3]. For example, associations have been found between allergic diseases and differences in the gut microflora among children in countries with a low and high prevalence of allergies[4]. Much evidence suggest that establishment of the gut microbiota plays an important role in directing immune system development. Such findings led to the microbial hypothesis, which states that exposure to microbes affect the development of the immune system and allergic diseases, to explain the hygiene hypothesis[5]. Given the immunological basis of allergic diseases and probiotic effects on immune system, probiotics have been investigated for their beneficial effect in preventing allergic diseases.

Changes in the gut microbiota can modulate immune response in distal organs, and studies suggest probiotics can alleviate allergic rhinitis[6,7]. Probiotics prevented the pollen-induced infiltration of white blood cells into the nasal mucosa and altered immune response in allergic rhinitis[6–8]. A study of young children (6–24 months) showed that orally taken Lactobacillus rhamnosus mildly decreased allergic sensitization[9]. Another study showed that Lactobacillus casei Shirota modulated immune response and alleviated the severity of symptoms in adult patients[10]. However, there are other studies showing few or no clinical benefits of probiotics[11]. Allergic rhinitis may be subdivided into different kinds and new studies that take this into consideration may provide clearer results.

Some studies report beneficial effect of probiotics for atopic dermatitis[12]. For children, it was especially effective when both prenatal and postnatal probiotics were used. Also, the preventive effect was greater in those with a family history of allergic diseases[13–18]. Meta-analyses suggest that there is convincing evidence for probiotics preventing the development of atopic dermatitis in high-risk infants but with varying degrees among the different disease subtypes and treatments[19–21]. At this point a preventive effect of probiotics is not confirmed but the results seem to show at least some benefits.

In a study with infants with atopic dermatitis, probiotics prevented asthma-like symptoms[22]. Another study showed that the clinical severity of asthma and allergic rhinitis decreased in the probiotic-treated patients compared to the controls, suggesting that probiotic supplementation may have clinical benefits for children with allergic airway diseases[23]. Although the possibility of using probiotics to treat asthma has been promising with animal models, no significant effect has been shown in human trials[24,25]. For example, in a study with 1223 mothers with infants at high risk for allergy, prenatal and postnatal use of probiotics did not have a preventive effect on asthma, although some allergic diseases occurred less in cesarean-delivered children receiving probiotics[26]. Similar results were shown in two other trials with no significant difference in terms of wheezing and prevalence[15,21]. In general, the results are affected by variables such as method of delivery, supplementation periods, and follow-up periods, which makes well-controlled trials very challenging.

The hygiene hypothesis and the microbial hypothesis suggest that the link between the immune system and the gut microbiota affects the development of allergic diseases. Currently the evidence is not strong enough to conclude that there is an absolute benefit. There are many contradicting results with confounding variables. However, collectively there has been a significant progress in understanding the mechanism behind how the gut microbiota can affect the human body and allergic diseases, and this can lead to new trials with more effective probiotics. Some of the proposed mechanisms will be discussed in the next article.

Sources

[1] Pwankar RC, Giorgio Walkter; Holgate, Stephen T.; Lockey, Richard F.: White Book on Allergy 2011–2012 Executive Summary. World Health Organization.

[2] Mannino DM, Homa DM, Pertowski CA, Ashizawa A, Nixon LL, Johnson CA, Ball LB, Jack E, Kang DS: Surveillance for asthma — United States, 1960–1995. MMWR CDC Surveill Summ 1998, 47:1–27.

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[7] Ouwehand AC, Nermes M, Collado MC, Rautonen N, Salminen S, Isolauri E: Specific probiotics alleviate allergic rhinitis during the birch pollen season. World J Gastroenterol 2009, 15:3261–3268.

[8] Wassenberg J, Nutten S, Audran R, Barbier N, Aubert V, Moulin J, Mercenier A, Spertini F: Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis. Clin Exp Allergy 2011, 41:565–573.

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[11] Koyama T, Kirjavainen PV, Fisher C, Anukam K, Summers K, Hekmat S, Reid G: Development and pilot evaluation of a novel probiotic mixture for the management of seasonal allergic rhinitis. Canadian Journal of Microbiology 2010, 56:730–738.

[12] Drago L, Iemoli E, Rodighiero V, Nicola L, De Vecchi E, Piconi S: Effects of Lactobacillus salivarius LS01 (DSM 22775) treatment on adult atopic dermatitis: a randomized placebo-controlled study. Int J Immunopathol Pharmacol 2011, 24:1037–1048.

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[16] Kukkonen K, Savilahti E, Haahtela T, Jutunen-Backman K, Korpela R, Poussa T: Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2007, 119.

[17] Kim JY, Kwon JH, Ahn SH, Lee SI, Han YS, Choi YO, Lee SY, Ahn KM, Ji GE: Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. Pediatr Allergy Immunol 2010, 21:e386–393.

[18] Brouwer ML, Wolt-Plompen SA, Dubois AE, van der Heide S, Jansen DF, Hoijer MA: No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial. Clin Exp Allergy 2006, 36.

[19] Kim NY, Ji GE: Effects of probiotics on the prevention of atopic dermatitis. Korean J Pediatr 2012, 55:193–201.

[20] Lee J, Seto D, Bielory L: Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. J Allergy Clin Immunol 2008, 121:116–121 e111.

[21] Taylor AL, Dunstan JA, Prescott SL: Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol 2007, 119.

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[24] Hougee S, Vriesema AJ, Wijering SC: Oral treatment with probiotics reduces allergic symptoms in ovalbumin-sensitized mice: a bacterial strain comparative study. Int Arch Allergy Immunol 2010, 151.

[25] Yu J, Jang SO, Kim BJ, Song YH, Kwon JW, Kang MJ, Choi WA, Jung HD, Hong SJ: The Effects of Lactobacillus rhamnosus on the Prevention of Asthma in a Murine Model. Allergy Asthma Immunol Res 2010, 2:199–205.

[26] Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Haahtela T, Savilahti E: Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Journal of Allergy and Clinical Immunology 2009, 123:335–341.