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Direct Evidence Supporting the Use of Specific Multi-Strain Probiotics in Allergic Rhinitis: A Research Review

Watts AM, Cox AJ, Smith PK, Besseling-Van Der Vaart I, Cripps AW, West NP. A specifically designed multispecies probiotic supplement relieves seasonal allergic rhinitis symptoms. J Altern Complement Med. 2018 Aug;24(8):833-840.


Allergic rhinitis (hay fever) is a chronic upper airway disease experienced by nearly 1 in 5 Australians (more than 4.6 million people) as of 2017-2018, based on reports from the Australian Institute of Health and Welfare (AIHW).1 The prevalence of allergic rhinitis is likely to have increased in the years since when accounting for major contributing factors of higher concentrations of airborne pollution, rising dust mite populations, less ventilation in homes and offices, dietary factors, and the trend toward more sedentary lifestyles.2 The severity of allergic rhinitis also exhibits seasonal and regional variation within Australia and New Zealand, linked to changes in the amount of pollen in the air.3-5


Allergic rhinitis is driven by an immunoglobulin E (IgE)-mediated response in the nasal mucosa upon allergen exposure.6 For symptomatic relief from runny nose, nasal congestion, sneezing, and itchy eyes and nose, hay fever sufferers often reach for antihistamines and nasal sprays. However, these are associated with sedation and don’t completely resolve symptoms. While immunotherapy may offer long-term resolution of symptoms, it too has its drawbacks since it is expensive and requires continuous treatment (>3 years).6,7


On the other hand, probiotics can help to prevent and manage the symptoms of allergic rhinitis by altering the composition of the gut microbiota and modifying host immunity.6 Specific probiotic strains have shown strong T helper 2 (Th2)-suppressive capabilities in a cell culture model.8 Other evidence shows that probiotics can influence the development of tolerogenic dendritic cells,9 stimulate toll-like receptors (TLRs) and promote immunosuppressive regulatory T cell (Treg) activity.10


Published Research on Specific Multi-Strain Probiotics


One study from Griffith University, Australia,6 sought to determine the proportion of participants with an improvement in the mini rhinoconjunctivitis quality of life questionnaire (mRQLQ) in response to specific multi-strain probiotics. It was a phase II intervention study that used a Simon two-stage design protocol that accounted for seasonal variation in symptoms. Probiotic treatment qualified as effective if at least 33% of participants responded positively to treatment. This means that at least 33% of participants needed to show at least a 0.7 U change in mRQLQ score for the treatment to be accepted as effective.


Adult allergic rhinitis sufferers consumed sachets containing 2 g of probiotics twice daily for eight weeks. The following six bacterial strains were present in the probiotic: Bifidobacterium bifidum W23, B. lactis W51, Lactobacillus acidophilus W55, L. casei W56, L. salivarius W57, and L. lactis W58 (total colony-forming units [CFU] 1x109/g), as well as vitamin B2 and biotin.6 These probiotic strains have been screened in vitro for their capacity to modulate production of immunosuppressive cytokines, specifically capable of inducing the production of interleukin (IL)-10 and interferon-gamma (IFN-γ) and reducing IL-4, IL-5 and IL-13.11


Secondary outcomes included assessment of change in symptoms and medication usage with a twice-weekly symptom and medication diary, nasal congestion via rhinomanometry, and total serum IgE and specific IgE for Bermuda grass.


A total of 40 participants completed the study, 25 (63%) of whom had a clinically meaningful response to treatment based on the mRQLQ (>0.7 U). Even after the first four weeks, half of the participants exhibited significant improvement in mRQLQ scores (see Figure 2).


The sum of individual symptom scores and overall symptom scores over the course of treatment was significantly reduced (p=0.036 and p=0.039, respectively) and a trend towards reduced frequency of allergy-related medication use was also observed (52.5% weeks 0 to 4 and 41.4% weeks 4 to 8; average proportion of total diary responses, p=0.085). Interestingly, responders were significantly more likely to be allergy medication users and have higher mRQLQ scores (i.e. greater disease severity) at baseline.


No significant changes in nasal resistance or IgE concentrations were observed.6 However, the observations of an improvement in allergic rhinitis symptoms without corresponding changes in serum IgE are consistent with other probiotic studies.12-15


The probiotic was well tolerated at the dose provided. Reported adverse events for all recruited participants were predominantly gastrointestinal in nature (i.e. change in bowel habits, feelings of excess bloating/gas or nausea) and short-lived, typically occurring within the first few weeks of treatment,6 which is consistent with other probiotic research.16,17


Figure 2. Mini Rhinoconjunctivitis Quality of Life Questionnaire (mRQLQ) Score Changes With Specific Multi-Strain Probiotics6


* indicates significant difference (p<0.05)


Clinical Takeaway


This study presents evidence to show that specific multi-strain probiotics may help to manage allergic rhinitis symptoms and lessen their impact on daily life when taken twice daily at the recommended dose.


References


1. Australian Institute of Health and Welfare. Allergic rhinitis ('hay fever') [Internet]. Canberra: Australian Government; 2020 [cited 2023 Aug 1]. Available from: https://www.aihw.gov.au/reports/chronic-respiratory-conditions/allergic-rhinitis-hay-fever/contents/allergic-rhinitis

2. Schoenwetter WF. Allergic rhinitis: epidemiology and natural history. Allergy Asthma Proc. 2000;21(1):1-6. DOI: 10.2500/108854100778248971

3. Allergy New Zealand. Pollen [Internet]. Auckland: Allergy New Zealand; 2023 [cited 2023 Aug 1]. Available from: https://www.allergy.org.nz/conditions/environmental-allergies/pollen/

4. Healthdirect. Pollen allergy [Internet]. Haymarket: Healthdirect; 2021 [cited 2023 Aug 1]. Available from: https://www.healthdirect.gov.au/pollen-allergy

5. Medek DE, Beggs PJ, Erbas B, Jaggard AK, Campbell BC, Vicendese D, et al. Regional and seasonal variation in airborne grass pollen levels between cities of Australia and New Zealand. Aerobiologia (Bologna). 2016 Jun;32(2):289-302. DOI: 10.1007/s10453-015-9399-x

6. Watts AM, Cox AJ, Smith PK, Besseling-Van Der Vaart I, Cripps AW, West NP. A specifically designed multispecies probiotic supplement relieves seasonal allergic rhinitis symptoms. J Altern Complement Med. 2018 Aug;24(8):833-840. DOI: 10.1089/acm.2017.0342

7. Meltzer EO, Rosario NA, Van Bever H, Lucio L. Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis. Allergy Asthma Clin Immunol. 2021 Nov;17(1):113. DOI: 10.1186/s13223-021-00614-6

8. Niers LEM, Timmerman HM, Rijkers GT, Van Bleek GM, Van Uden NOP, Knol EF, et al. Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines. Clin Exp Allergy. 2005 Nov;35(11):1481-1489. DOI: 10.1111/j.1365-2222.2005.02375.x

9. Niers LEM, Hoekstra MO, Timmerman HM, Van Uden NO, De Graaf PMA, Smits HH, et al. Selection of probiotic bacteria for prevention of allergic diseases: immunomodulation of neonatal dendritic cells. Clin Exp Immunol. 2007 Aug;149(2):344-352. DOI: 10.1111/j.1365-2249.2007.03421.x

10. Ozdemir O. Various effects of different probiotic strains in allergic disorders: an update from laboratory and clinical data. Clin Exp Immunol. 2010 Jun;160(3):295-304. DOI: 10.1111/j.1365-2249.2010.04109.x

11. Winclove Probiotics. Ecologic® ALLERGYCARE technical data sheet: managing allergic symptoms; hay fever and eczema [Internet]. Amsterdam: Winclove Probiotics; 2023 [cited 2023 Aug 1]. Available from: https://www.knowde.com/stores/winclove-probiotics/documents/270104

12. Dennis-Wall JC, Culpepper T, Nieves C, Rowe CC, Burns AM, Rusch CT, 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 Mar;105(3):758-767. DOI: 10.3945/ajcn.116.140012

13. Kawase M, He F, Kubota A, Hiramatsu M, Saito H, Ishii T, et al. Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study. Int J Food Microbiol. 2009 Jan;128(3):429-434. DOI: 10.1016/j.ijfoodmicro.2008.09.017

14. Ishida Y, Nakamura F, Kanzato H, Sawada D, Hirata H, Nishimura A, et al. Clinical effects of Lactobacillus acidophilus strain L-92 on perennial allergic rhinitis: a double-blind, placebo-controlled study. J Dairy Sci. 2005 Feb;88(2):527-533. DOI: 10.3168/jds.S0022-0302(05)72714-4

15. Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001 Apr;357(9262):1076-1079. DOI: 10.1016/S0140-6736(00)04259-8

16. Zajac AE, Adams AS, Turner JH. A systematic review and meta-analysis of probiotics for the treatment of allergic rhinitis. Int Forum Allergy Rhinol. 2015 Jun;5(6):524-532. DOI: 10.1002/alr.21492

17. Cox AJ, West NP, Horn PL, Lehtinen MJ, Koerbin G, Pyne DB, et al. Effects of probiotic supplementation over 5 months on routine haematology and clinical chemistry measures in healthy active adults. Eur J Clin Nutr. 2014 Nov;68(11):1255-1257. DOI: 10.1038/ejcn.2014.137







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