Application of probiotics in the treatment of allergic rhinitis

Allergic rhinitis is a common allergic reaction to small particles in the air that, when inhaled, stimulates the body to release a natural chemical called histamine. Common triggers include dust mites, mold, pet dander, and pollen from trees. Symptoms of allergic rhinitis include sneezing, nasal congestion, and allergic inflammation of the nose, throat, mouth, and eyes. Allergic rhinitis is different from the common cold. It can occur at any time of the year. Allergic rhinitis is a highly prevalent condition. In the United States, about 15% to 20% of the population have allergic rhinitis. Millions of children and adults suffer from allergic rhinitis every year. Allergic rhinitis significantly affects daily life, causing discomfort and irritability. Therefore, there is a need for effective methods to minimize allergic rhinitis. Probiotic therapy is considered safe and effective in supporting the reduction of allergic rhinitis.

What is allergic rhinitis?

 Allergic rhinitis is a common non-infectious form of rhinitis characterized by the presence of symptoms such as itching (eyes, nose, or mouth), sneezing, runny nose, and nasal congestion. The nasal mucosa becomes congested, swells, and produces excess fluid. Allergic rhinitis can occur seasonally or year-round because of allergens such as pollen, animal dander, dust (Figure 1). Although it is a benign condition, allergic rhinitis significantly affects the quality of life by affecting sleep, work, and learning abilities [1]. In some cases, severe complications related to asthma symptoms may occur [2]. According to the International Study of Asthma and Allergies in Childhood (ISAAC), allergic rhinitis affects 10-40% of the global population, with an average prevalence rate in adults (>18 years old) of 29.8%, balanced in both men and women. In children, the prevalence ranges from 8% to 15%, varying with age, and the disease is more common in males than in females. Children with a family history of allergies are more likely to develop the condition and at a younger age than children without allergies [3, 4].

Improving the quality of life, rapidly reducing symptoms, preventing relapse, and ensuring treatment safety are the objectives of allergic rhinitis treatment [2]. To treat allergic rhinitis, the primary options include allergen avoidance, antihistamines, vasoconstrictors, corticosteroids, and probiotics (probiotic supplements) [1, 5-7]. Using probiotics in the treatment of allergic rhinitis is a widely studied and applied approach based on the immunomodulatory properties of these microorganisms when present in the host’s body [6, 8].

Figure 1: Allergens causing allergic rhinitis in the environment

Causes of Allergic Rhinitis

Allergic rhinitis results from the body’s immune system, reacting to allergens from the environment entering the nose. In the nasal cavity, the nasal mucosa plays a role in regulating temperature, humidity, and air purification. The outer layer of the mucous membrane consists of ciliated cells, mucus-secreting cells that can interact with allergens from the outside and bind to the immune system. Below the mucosa are blood vessels, mucus, nerve networks, blood vessels, and cell networks [9, 10]. When an allergen enters the nose, the epithelial cells of the nasal mucosa capture it. The protease activity of the allergen cuts the connections in the epithelial tissue, leading to damage/activation of the epithelial cells and release of cytokines such as TSLP, IL33, IL25, and chemokines that directly affect the cells in the lower layer of the nasal mucosa, such as innate lymphoid cells (ILC2), Th2 helper T cells, or antigen-presenting cells (APC) (Figure 2) [7, 11, 12]. APCs capture antigens and present them to Th0 lymphocytes, which can differentiate into Th2 lymphocytes. Th2 lymphocytes release cytokines IL4, IL5, and IL13, which activate B lymphocytes to produce specific IgE antibodies against allergens. These IgE antibodies circulate and bind to their receptors on mast cells and eosinophils, activating these cells to release cytokines and inflammatory mediators such as histamine and leukotrienes [13]. These substances also help drive the immune response, with Th2 lymphocytes predominating, leading to an increased production of IgE and a more severe inflammatory process [7, 10, 14]. In summary, an immune response mediated by IgE results in allergic rhinitis, which is closely related to the imbalance of Th1/Th2 lymphocytes [12].

Figure 2: Allergic immune reaction in the nasal mucosa upon exposure to allergens

Treatment of Allergic Rhinitis

Current treatments such as antihistamines or corticosteroids are very effective in inhibiting/reducing the production of cytokines or inflammatory mediators that promote the formation of Th2 cells but have many side effects such as drowsiness, cognitive impairment, increased blood pressure, and developmental disorders [15]. The use of probiotics in the treatment of allergic rhinitis is a researched and applied solution based on the immune-modulating properties of these probiotic strains when present in the host body.

The anti-allergic mechanism of probiotics involves regulating the expression of cytokines that inhibit the formation of Th2 cells, such as IL10, IL12, TGF-β, and IFN-γ, thereby reducing the production of IgE [16]. Analysis of the gene system of the Lactobacillus plantarum strain revealed 6 genes encoding N-acetyl-glucosamine/galactosamine phosphotransferase, which transport bacteriocin that promotes the production of IL10 and IL12 in the peripheral blood of allergic patients [17]. The results of using the probiotic NVP-1703, containing two strains of L. plantarum and Bifidobacterium longum at a dosage of 1.0 × 10¹⁰ CFU/day, on 47 allergic rhinitis patients aged 19-65 years for 4 weeks showed a significant reduction in IgE antibodies and an increase in the presence of IL10 in the blood compared to the non-probiotic group [16]. At the same time, the symptoms of allergic rhinitis also decreased in the probiotic group. According to the clinical evaluation by Singh et al. in 2013, the use of the probiotic B. lactis NCC2818 in the treatment of allergic rhinitis patients with grass pollen allergies, aged 10–65 years, at a dosage of 4 × 10⁹ CFU/day, resulted in a significant decrease in the levels of cytokines produced by Th2 cells, such as IL5 and IL13, in the blood of allergic rhinitis patients, and higher scores in terms of rhinitis control (RCAT) compared to the non-probiotic group [5]. Two clinical trials using a probiotic mixture of 4 bacterial strains, L. gasseri KS-13, B. bifidum G9-1, and B. longum MM-2, for the treatment of seasonal allergic rhinitis in children for 8 weeks at a dosage of 1.5 × CFU/day, showed no significant differences in IgE antibody levels and Treg lymphocyte percentages between the two groups. However, they significantly improved the symptoms of allergic rhinitis, such as runny nose and nasal congestion, in the probiotic group [6, 18, 19].

In conclusion, the use of probiotics in the treatment of allergic rhinitis helps reduce the symptoms of the disease and improves quality of life. To date, researchers have reported none serious side effects. This is a promising novel treatment approach with many advantages compared to traditional treatment methods. However, we need to conduct further research on the safety, mechanisms, and efficacy of probiotics in treating allergic rhinitis. A healthcare professional should monitor and guide all probiotic treatments for allergic rhinitis.

References

1. Bachert, C., et al., Allergic Rhinitis and its impact on asthma update (ARIA 2008). The Belgian perspective. B-ENT, 2008. 4(4): p. 253-7.
2. Bousquet, J., et al., Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol, 2012. 130(5): p. 1049-62.
3. Singh, K., S. Axelrod, and L. Bielory, The epidemiology of ocular and nasal allergy in the United States, 1988-1994. J Allergy Clin Immunol, 2010. 126(4): p. 778-783 e6.
4. Kurukulaaratchy, R.J., et al., The influence of gender and atopy on the natural history of rhinitis in the first 18 years of life. Clin Exp Allergy, 2011. 41(6): p. 851-9.
5. Singh, A., et al., Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial. Eur J Clin Nutr, 2013. 67(2): p. 161-7.
6. Steiner, N.C. and A. Lorentz, Probiotic Potential of Lactobacillus Species in Allergic Rhinitis. Int Arch Allergy Immunol, 2021. 182(9): p. 807-818.
7. Hajavi, J., et al., The immunomodulatory role of probiotics in allergy therapy. J Cell Physiol, 2019. 234(3): p. 2386-2398.
8. Yang, G., Z.Q. Liu, and P.C. Yang, Treatment of allergic rhinitis with probiotics: an alternative approach. N Am J Med Sci, 2013. 5(8): p. 465-8.
9. Rock, J.R., Scott H. Randell, and Brigid LM Hogan, Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Disease models & mechanisms, 2010. 3: p. 545-556.
10. Eifan, A.O., and Stephen R. Durham, Pathogenesis of rhinitis. Clinical & Experimental Allergy, 2016. 46: p. 1139-1151.
11. Min, H.J., et al., Th2 cytokines-DUOX2-ROS-HMGB1 translocation axis is important in the pathogenesis of allergic rhinitis. Clin Sci (Lond), 2021. 135(3): p. 483-494.
12. Akdis, M., Johan Verhagen, Alison Taylor, Fariba Karamloo, Christian Karagiannidis, Reto Crameri, Sarah Thunberg et al, Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. The Journal of experimental medicine, 2004. 11: p. 1567-1575.
13. Jutel, M., M. Akdis, and C. A. Akdis, Histamine, histamine receptors and their role in immune pathology. Clinical & Experimental Allergy, 2009. 39: p. 1786-1800.
14. Haenuki, Y., et al., A critical role of IL-33 in experimental allergic rhinitis. J Allergy Clin Immunol, 2012. 130(1): p. 184-94 e11.
15. Church, M.K. and D.S. Church, Pharmacology of antihistamines. Indian J Dermatol, 2013. 58(3): p. 219-24.
16. Kang, M.G., et al., Probiotic NVP-1703 Alleviates Allergic Rhinitis by Inducing IL-10 Expression: A Four-week Clinical Trial. Nutrients, 2020. 12(5).
17. Yan, F. and D.B. Polk, Probiotics and immune health. Curr Opin Gastroenterol, 2011. 27(6): p. 496-501.
18. Dennis-Wall, J.C., et al., Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial. Am J Clin Nutr, 2017. 105(3): p. 758-767.
19. Vliagoftis, H., et al., Probiotics for the treatment of allergic rhinitis and asthma: systematic review of randomized controlled trials. Ann Allergy Asthma Immunol, 2008. 101(6): p. 570-9.