Probiotics in Allergy Treatment

Probiotics are composed of specific live microorganisms or bacterial communities aimed at promoting health benefits or enhancing the immune activity of the host. Different strains and combinations of microorganisms in the gut are believed to influence the risk of developing allergies [1]. The escalating global prevalence of allergies marks a concern for community health, particularly among children and urban dwellers. Allergies represent hypersensitive reactions initiated by immune mechanisms through intermediate contact with allergens (the triggering antigens) [2]. Such allergies are often categorized into antibody-mediated or cell-mediated intermediaries [1]. The role of probiotics or prebiotics in selectively stimulating beneficial bacteria has been evaluated in studies addressing allergies [3,4]. However, in the current era, there isn’t sufficient evidence to officially recommend probiotics in preventing specific allergies or allergic conditions in children [5].

Approximately 1 billion people worldwide suffer from allergies, which is estimated to reach 4 billion in the next 30–40 years [6]. While no definitive determining risk factor has been identified, environmental factors such as smoking, air pollution, and exposure to allergens are considered explanations for observed changes in disease prevalence [7,8]. Reduced exposure to microorganisms, dietary alterations, or increased antibiotic usage could also be determining factors in escalating allergy rates [9]. Allergic individuals develop immunoglobulin E (IgE) antibodies as a response to regular exposure to allergenic substances (often proteins), leading to typical symptoms like asthma, rhinitis, and eczema. However, not all cases are IgE-mediated. Mechanisms driving increased disease prevalence, not yet fully understood, may involve genetic factors and complex interactions between the host and exposure to allergens, as well as other environmental stimuli like the gut microbiota and infectious agents [1].

Traditional and Modern Medicine in Allergy Treatments

Generally, healthcare facilities often prescribe medications directly affecting the body’s disease-causing mechanisms, including steroids, leukotriene antagonists, antihistamines, bronchodilators, and IgE antibody inhibitors. Or, in severe allergic reactions, emergency medications like auto-injectable adrenaline pens, such as the EpiPen, are used. However, the use of these medications often presents issues like fatigue, nausea, dry mouth, and blurred vision, affecting excretory functions, leading to the conclusion that these medications still pose certain existence of side effects, efficacy, and costs.

To avoid adverse effects from chemical constituents, some researchers have proposed experimenting with herbal medicine and acupuncture to regulate the body’s immune system. Several studies have focused on exploring the therapeutic potential of these complementary methods in immune-related diseases. In 2015, Bi-Fong Lin and colleagues presented evidence using herbal extracts to enhance anti-inflammatory activities and immune stimulation in treating asthma, along with other evidence suggesting herbal extracts’ ability to reduce respiratory inflammation. However, the test subjects did not show significant improvement in allergic asthma symptoms after treatment [10]. Further research into these medications and herbal methods is necessary to identify new compounds and treatment approaches.

Figure 1: Treatments of allergies

The Relationship between Allergies and the Gut Microbiota

Allergies occur due to various factors, but gut microbiota and diet changes are perhaps the most critical factors. We all know that the gut contains a significant portion of the immune system, so any dysfunction in the gut can lead to bodily symptoms. Early exposure to microorganisms alters the balance of T helper cell cytokines, specifically the Th1/Th2 types, increasing Th1 responses. When newborns have an underdeveloped immune system, they tend to use Th2 to prevent rejection in the womb. However, Th2 leads to stimulating IgE production, increasing the risk of allergic reactions. Early exposure to microorganisms in infancy reverses the effects of Th2, stimulates Th1, and triggers Th3 cell activity. This results in IgA production by B cells. IgA contributes to the exclusion of allergens, reducing the immune system’s exposure to antigens. Cytokines produced by Th1 also reduce inflammation and stimulate tolerance to regular antigens [1]. Thus, allergic disorders related to the imbalance of Th1/Th2 cytokines lead to Th2 cytokine activation and simultaneously release interleukin-4 (IL-4), IL-5, and IL-13, similar to IgE production.

Figure 2: Mechanism of allergic reactions by immune cells [14]

Probiotics alter the gut environment, enhance the body’s defense against harmful microorganisms, and secrete cytokines that can modulate Toll-like receptors and intestinal proteoglycans, activating dendritic cells and Th1 cells. As a result, Th2 responses are inhibited. Bacterial strains belonging to the Lactobacillus family are often studied in probiotics. They possess characteristics such as adhering to intestinal epithelial tissue to prevent pathogen invasion, competing with harmful species, and secreting substances to hinder or eliminate pathogens. L. casei Shirota is used as a biological agent to stimulate the immune response and prevent intestinal bacterial infections. Lactobacillus GG is also used as an effective oral vaccine against rotavirus. Several in vitro and animal studies have investigated the effects of probiotics on allergies. When pregnant women with a family history of eczema, allergic rhinitis, or asthma and their infants were given Lactobacillus GG in the first 6 months, the frequency of allergic dermatitis in infants decreased by 50%, 44%, and 36% after 2, 4, and 7 years, respectively [1]. In 2017, a randomized controlled trial reported significant improvements in allergic symptoms in allergic rhinitis with concurrent asthma when treated with probiotics, compared to the placebo group, which experienced worsened allergic symptoms and decreased quality of life [11]. In a clinical trial, individuals consuming yogurt supplemented with probiotics exhibited reduced inflammatory molecule levels and immune cells related to eosinophils, along with significant improvements in allergic eye symptoms (but not nasal or throat symptoms) [11].

The Mechanism of Probiotics in Allergies

Reports on the use of probiotics to reduce or treat other diseases have also been extensively documented. Giovannini et al. [12] revealed that L. casei reduced episodes of rhinitis in 64 preschool children with allergic rhinitis in some cases. For asthma, L. casei showed little change in disease status and only positive outcomes in children with allergic rhinitis. Regarding food-related allergies, probiotics were found to maintain intestinal epithelial barrier integrity, inhibit inflammatory reactions, and stimulate IgA production in immune responses [1]. Following this trial, Hol et al. also reported that probiotics did not improve tolerance in 119 children allergic to cow’s milk [13]. Other studies conducted on children allergic to peanuts, eggs, or milk treated with probiotics for three months showed no promising results. A World Allergy Organization Special Committee on Food Allergy and Nutrition concluded that probiotics do not prevent or treat allergies definitively [12]. The varying outcomes from studies on the efficacy of probiotics in preventing and treating allergies may be due to differences in bacterial strains, treatment duration, and dosage. These differences also depend on host factors, environmental influences, individual gut microbiota, patient diets with prebiotic substances, and antibiotic treatments.

In conclusion, probiotics may have a potential role in preventing and treating allergies, but further studies are needed at this current time. These studies should aim to gain a deeper understanding and refine current knowledge systems to harness the potential of probiotics in allergy management.

References:

1. Tang, R.B., Chang, J.K. and Chen, H.L., 2015. Can probiotics be used to treat allergic diseases?. Journal of the Chinese Medical Association, 78(3), pp.154-157.
2. Johansson, S.G.O., Bieber, T., Dahl, R., Friedmann, P.S., Lanier, B.Q., Lockey, R.F., Motala, C., Martell, J.A.O., Platts-Mills, T.A., Ring, J. and Thien, F., 2004. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. Journal of allergy and clinical immunology, 113(5), pp.832-836.
3. Tang, M.L., Lahtinen, S.J. and Boyle, R.J., 2010. Probiotics and prebiotics: clinical effects in allergic disease. Current opinion in pediatrics, 22(5), pp.626-634.
4. Nowak-Węgrzyn, A. and Muraro, A., 2011. Food allergy therapy: is a cure within reach?. Pediatric Clinics, 58(2), pp.511-530.
5. Yao, T.C., Chang, C.J., Hsu, Y.H. and Huang, J.L., 2010. Probiotics for allergic diseases: realities and myths. Pediatric allergy and immunology, 21(6), pp.900-919.
6. Spacova, I., Ceuppens, J.L., Seys, S.F., Petrova, M.I. and Lebeer, S., 2018. Probiotics against airway allergy: host factors to consider. Disease models & mechanisms, 11(7), p.dmm034314.
7. Liu, M.Y., Yang, Z.Y., Dai, W.K., Huang, J.Q., Li, Y.H., Zhang, J., Qiu, C.Z., Wei, C., Zhou, Q., Sun, X. and Feng, X., 2017. Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced airway asthma and β-lactoglobulin-induced intestinal food allergy mouse models. World Journal of Gastroenterology, 23(12), p.2149.
8. Strachan, D.P., 1989. Hay fever, hygiene, and household size. BMJ: British Medical Journal, 299(6710), p.1259.

9. Joyce, E.Y. and Miller, R.L., 2016. Got milk? Understanding the farm milk effect in allergy and asthma prevention. Journal of Allergy and Clinical Immunology, 137(6), pp.1707-1708.
10. Lopez-Santamarina, A., Gonzalez, E.G., Lamas, A., Mondragon, A.D.C., Regal, P. and Miranda, J.M., 2021. Probiotics as a possible strategy for the prevention and treatment of allergies. A narrative review. Foods, 10(4), p.701.
11. Miraglia Del Giudice, M., Indolfi, C., Capasso, M., Maiello, N., Decimo, F. and Ciprandi, G., 2017. Bifidobacterium mixture (B longum BB536, B infantis M-63, B breve M-16V) treatment in children with seasonal allergic rhinitis and intermittent asthma. Italian journal of pediatrics, 43(1), pp.1-6.
12. Giovannini, M., Agostoni, C., Riva, E., Salvini, F., Ruscitto, A., Zuccotti, G.V. and Radaelli, G., 2007. A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in pre-school children with allergic asthma and/or rhinitis. Pediatric research, 62(2), pp.215-220.
13. Hol, J., van Leer, E.H., Schuurman, B.E.E., de Ruiter, L.F., Samsom, J.N., Hop, W., Neijens, H.J., de Jongste, J.C. and Nieuwenhuis, E.E., 2008. The acquisition of tolerance toward cow’s milk through probiotic supplementation: a randomized, controlled trial. Journal of Allergy and Clinical Immunology, 121(6), pp.1448-1454.

14. GONZALEZ-DE-OLANO, D.; ÁLVAREZ-TWOSE, I. Mast cells as key players in allergy and inflammation. Journal of Investigational Allergology & Clinical Immunology, 2018, 28.6: 365-378.