The Role of Live Bacteria Supplements in Allergic Diseases

This informal CPD article, ‘The Role of Live Bacteria Supplements in Allergic Diseases,’ was provided by ADM Protexin, who are dedicated to producing innovative, research based live bacteria (Probiotic) products for the veterinary, human, agriculture and equine healthcare markets.

What is allergy?

Allergy is defined as an “immunologically mediated hypersensitivity leading to disease”.¹ Worldwide, approximately 1 billion people suffer with allergies and this figure is expected to rise over the next 30 years.^2,3 The cause is posited to be a malfunction of the immune system, in which harmless environmental or food substances are interpreted as being harmful, causing the immune system to overreact.⁴ It appears that allergic conditions are often interlinked, with common immune and gut alterations observed.⁵ Currently, standard treatments for allergies include medications to supress the immune system and strict avoidance of the triggering substance.⁶ However, many medications possess side effects, including altering microbial diversity,⁷ therefore many sufferers are looking for alternative solutions.

Allergy and the microbiome

Microbes are found throughout most tissues in the body and are collectively defined as the microbiome.^8,9 The gut mucosa houses approximately 70% of the body’s active immune cells,¹⁰ comprising the largest component of the immune system.¹¹ These immune cells are influenced by the trillions of live bacteria that reside there.

Live bacteria have been shown to have modulatory effects upon the immune system with specific strains either stimulating or dampening immune responses.¹² Dysbiosis (a quantitative and/or qualitative imbalance in the microflora) has been observed in those suffering allergic diseases.¹³ The microbiome is thought to influence the balance between T-helper cells 1 and 2 (Th1, Th2), where Th2 dominance leads to higher IgE-mediated immune activation.¹⁴ This heightened immune activity can contribute to increased gut permeability, allowing the passage of toxins, antigens and bacteria from the gut lumen to the blood stream, which subsequently stimulates the immune system.¹⁵ This state has been observed in many of those suffering with allergic conditions.^14,16–19 Live bacteria supplementation may provide an avenue of therapeutic consideration for allergies due to their ability to reduce inflammation, restore gut-barrier integrity and modulate immune signalling.^14,20

Atopic Dermatitis

Atopic dermatitis (AD), also known as eczema, is the most common chronic inflammatory skin disease that occurs in early life, with a prevalence of around 20% in children.²⁰ It typically presents as dry, itchy and inflamed skin.²¹ A combination of impaired skin barrier function and immune dysregulation is a hallmark of AD, which favours an altered skin and gut microbiome.^22–24 Reddel et al. (2019)²⁴ reported that children with AD were found to have a reduction or complete absence in certain bacteria associated with immune modulation and inflammation. Evidence suggests balancing the bacterial composition within the gut and therefore the skin, may interfere with the further development of other IgE mediated immune reactions. The further progression of these responses is referred to as the ‘atopic march’^21,22 which describes atopic dermatitis as being the preceding condition that may sequentially lead to food allergies, asthma or allergic rhinitis (AR).²⁵

Due to the broad range of bacterial species that may possess a beneficial effect, research has so far struggled to arrive at a consensus regarding specific strains, strength, dosage and time of intervention in order to prevent and aid eczema.²⁶ This has resulted in mixed study outcomes.²⁷ Live bacteria may promote a healthy microbiome by influencing optimal immune balance and preventing colonisation by pathogenic bacteria. Collectively, it is thought these elements could potentially improve the aetiology of the condition.^24,28

Asthma

Asthma is an inflammatory condition associated with the lower airways, characterised by wheezing, shortness of breath, chest tightness and coughing.²⁹ The airways contain epithelial mucosa and dendritic cells, as well as antimicrobial compounds. These components form the basis for immune regulation through modulating IgA antibodies, defensins, lysozymes and interleukins. If required, these immune cells are able to stimulate the pro-inflammatory Th2 reaction that favours the development of asthma.³⁰

A diverse microbiome is often found within the lungs of healthy cohorts, with dysbiosis commonly observed in those suffering with asthma.³¹ From birth throughout the entire life span, a close correlation between the composition of the gut and lung microbiota exists, suggesting a host-wide network,³² and it has been suggested that both the gut and lungs may function as a single organ, sharing immunological functions.¹³ Communication is thought to occur via the gut-lung axis, involving cross-talk between fungi and bacteria, which may influence health and disease states within respiratory conditions.³³ However, the use of live bacteria in asthma is another area where mixed study results are observed.³⁴ As Wang et al. (2019)³⁵ concludes, many trials are now recording specific strains of bacteria used, therefore as studies become more sophisticated, there may be future development in this field.

Allergic Rhinitis

Allergic rhinitis (AR), otherwise known as hay fever, affects up to 20% of the global population and involves inflammation of the upper respiratory tract.³⁶ AR is characterised by a drive towards Th2 cytokines, as with other allergic conditions. A review by Myles (2019)³⁷ notes that although a genetic predisposition is apparent with AR, there are limited conventional preventive recommendations for sufferers other than avoiding known allergens. He goes on to suggest that, consideration of nutritional interventions, stress management and environmental modifications may well expand the therapeutic approach. Live bacteria may be a suitable candidate to be included here. Whilst there are a limited number of studies, positive outcomes have been recorded, including reductions in inflammatory markers and symptoms.^38–40 For example, live bacteria have been found to reduce inflammatory markers such as interleukin (IL)-5, IL-8, TNF-α, IL-1β and IL-13 as well as increase anti-inflammatory IL-10,⁴¹ and improve hay fever symptoms such as nasal congestion, sneezing, eye redness, weeping and itching.^42–45

Food Allergy

Classic food allergy involves an IgE-mediated response and may become apparent immediately with hypersensitivity,¹⁴ displaying possible symptoms of rash, wheezing, tongue and lip swelling and chest pain.⁴⁶ Food allergy has been described as a failure of oral tolerance, which is developed throughout infancy.¹⁴ Oral tolerance will determine whether a T-helper cell (immune reaction) or a T-regulatory cell (tolerance) is matured when exposed to a food.⁴⁶ Several factors are noted as being associated with food allergy, such as caesarean section birth, low fibre diet, breastfeeding and antibiotic therapy.¹³ These factors are also associated with a shift in gut bacterial load and diversity, therefore dysbiosis may be implicated.¹³

Studies on the use of live bacteria in food allergy are yet to be developed with consistent methodologies to allow for comparison. However, some studies have shown promising results with peanut and cow’s milk allergy alongside bacteria (L. rhamnosus in particular).³⁵ As sufferers with food allergies are often observed to have different microbial signatures, the pathogen inhibition effect of live bacteria supplementation may provide a useful mechanism of action, in addition to anti-inflammatory properties.^{13, 14, 47}

Conclusion

Throughout current research involving live bacteria and allergies, great emphasis is placed upon the importance of the ‘critical window’ of immune development. Notably, the first 1000 days of life is becoming a widely accepted determinant of microbiome establishment and consequent immune maturation.⁴⁸ This is not to suggest that introduction of microbes later in life does not serve benefit, because education of the immune response is a lifelong process.⁴⁹ Modern living practices such as urbanised living environments, pre and postpartum behaviour (breast-feeding, skin contact etc.), antibiotic therapy, diet, exercise and personal care products need to be further understood for their potential impact upon microbiota diversity, and its subsequent influence upon immunity and allergy.⁵⁰ Whilst further clinical trials are needed, modulation of the gut microbiome via live bacteria supplementation is providing insight into possible strategies for prevention and intervention in a number of common allergic conditions.

We hope this article was helpful. For more information from ADM Protexin, please visit their CPD Member Directory page. Alternatively, you can go to the CPD Industry Hubs for more articles, courses and events relevant to your Continuing Professional Development requirements.

References:

1 Mechanisms of immune regulation in allergy. DOI:10.5167/uzh-140934.

2 Pawankar R. Allergic diseases and asthma: A global public health concern and a call to action. World Allergy Organ. J. 2014; 7: 12.

3 Forsberg A, West CE, Prescott SL, Jenmalm MC. Pre- and probiotics for allergy prevention: time to revisit recommendations? Clin. Exp. Allergy. 2016; 46: 1506–21.

4 Allergies: Overview - InformedHealth.org - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK447112/ (accessed April 29, 2020).

5 Polkowska-Pruszy-ska B, Gerkowicz A, Krasowska D. The gut microbiome alterations in allergic and inflammatory skin diseases – an update. J Eur Acad Dermatology Venereol 2020; 34: 455–64.

6 Food allergy | Treatment summary | BNF content published by NICE. https://bnf.nice.org.uk/treatment-summary/food-allergy.html (accessed April 29, 2020).

7 Bhat M, Pasini E, Copeland J, et al. Impact of Immunosuppression on the Metagenomic Composition of the Intestinal Microbiome: A Systems Biology Approach to Post-Transplant Diabetes. Sci Rep 2017; 7. DOI:10.1038/s41598-017-10471-2.

8 Dieterich W, Schink M, Zopf Y. Microbiota in the Gastrointestinal Tract. Med Sci 2018; 6: 116.

9 Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the human microbiome. Nutr Rev 2012; 70: S38.

10 Vighi G, Marcucci F, Sensi L, Di Cara G, Frati F. Allergy and the gastrointestinal system. Clin. Exp. Immunol. 2008; 153: 3–6.

11 Mowat AM, Agace WW. Regional specialization within the intestinal immune system. Nat. Rev. Immunol. 2014; 14: 667–85.

12 Liu Y, Alookaran JJ, Rhoads JM. Probiotics in autoimmune and inflammatory disorders. Nutrients. 2018; 10. DOI:10.3390/nu10101537.

13 Pascal M, Perez-Gordo M, Caballero T, et al. Microbiome and allergic diseases. Front. Immunol. 2018; 9. DOI:10.3389/fimmu.2018.01584.

14 Sharma G, Im SH. Probiotics as a potential immunomodulating pharmabiotics in allergic diseases: Current status and future prospects. Allergy, Asthma Immunol. Res. 2018; 10: 575–90.

15 Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Front. Immunol. 2017; 8. DOI:10.3389/fimmu.2017.00598.

16 Lee SY, Lee E, Park YM, Hong SJ. Microbiome in the gut-skin axis in atopic dermatitis. Allergy, Asthma Immunol. Res. 2018; 10: 354–62.

17 Samadi N, Klems M, Untersmayr E. The role of gastrointestinal permeability in food allergy. Ann. Allergy, Asthma Immunol. 2018; 121: 168–73.

18 Walker J, Dieleman L, Mah D, Park K, Meddings J, Vethanayagam D. High prevalence of abnormal gastrointestinal permeability in moderate-severe asthma. Clin Investig Med 2014; 37. DOI:10.25011/cim.v37i2.21086.

19 Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016; 4. DOI:10.1080/21688370.2016.1251384.

20 La Fata G, Weber P, Mohajeri MH. Probiotics and the Gut Immune System: Indirect Regulation. Probiotics Antimicrob. Proteins. 2018; 10: 11–21.

21 Kapur S, Watson W, Carr S. Atopic dermatitis. Allergy, Asthma Clin. Immunol. 2018; 14. DOI:10.1186/s13223-018-0281-6.

22 Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: probiotics in dermatology. Br J Dermatol 2019; 182: bjd.18088.

23 Baviera G, Leoni MC, Capra L, et al. Review Article Microbiota in Healthy Skin and in Atopic Eczema. 2014. DOI:10.1155/2014/436921.

24 Reddel S, Del Chierico F, Quagliariello A, et al. Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture. Sci Rep 2019; 9: 1–10.

25 Paller AS, Spergel JM, Mina-Osorio P, Irvine AD. The atopic march and atopic multimorbidity: Many trajectories, many pathways. J Allergy Clin Immunol 2019; 143: 46–55.

26 Rather IA, Bajpai VK, Kumar S, Lim J, Paek WK, Park YH. Probiotics and atopic dermatitis: An overview. Front. Microbiol. 2016; 7. DOI:10.3389/fmicb.2016.00507.

27 Makrgeorgou A, Leonardi-Bee J, Bath-Hextall FJ, et al. Probiotics for treating eczema. Cochrane Database Syst. Rev. 2018; 2018. DOI:10.1002/14651858.CD006135.pub3.

28 Kim HW, Hong R, Choi EY, et al. A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice. Front Microbiol 2018; 9: 2414.

29 Quirt J, Hildebrand KJ, Mazza J, Noya F, Kim H. Asthma. Allergy, Asthma Clin. Immunol. 2018; 14. DOI:10.1186/s13223-018-0279-0.

30 Frati F, Salvatori C, Incorvaia C, et al. The role of the microbiome in asthma: The gut–lung axis. Int. J. Mol. Sci. 2019; 20. DOI:10.3390/ijms20010123.

31 Hilty M, Burke C, Pedro H, et al. Disordered Microbial Communities in Asthmatic Airways. PLoS One 2010; 5: e8578.

32 Grier A, McDavid A, Wang B, et al. Neonatal gut and respiratory microbiota: Coordinated development through time and space. Microbiome 2018; 6. DOI:10.1186/s40168-018-0566-5.

33 Enaud R, Prevel R, Ciarlo E, et al. The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks. Front. Cell. Infect. Microbiol. 2020; 10. DOI:10.3389/fcimb.2020.00009.

34 Moura JCV, Moura ICG, Gaspar GR, et al. The use of probiotics as a supplementary therapy in the treatment of patients with asthma: a pilot study and implications. Clinics 2019; 74.

35 Wang HT, Anvari S, Anagnostou K. The Role of Probiotics in Preventing Allergic Disease. Children 2019; 6: 24.

36 Small P, Keith PK, Kim H. Allergic rhinitis. Allergy, Asthma Clin. Immunol. 2018; 14. DOI:10.1186/s13223-018-0280-7.

37 Myles IA. Allergy as a disease of dysbiosis: Is it time to shift the treatment paradigm? Front. Cell. Infect. Microbiol. 2019; 9. DOI:10.3389/fcimb.2019.00050.

38 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; 5: 524–32.

39 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.

40 Do probiotics have a role in the treatment of allergic rhinitis? A comprehensive systematic review and meta-analysis. - PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/27442711 (accessed May 15, 2020).

41 Yang G, Liu ZQ, Yang PC. Treatment of allergic rhinitis with probiotics: An alternative approach. N. Am. J. Med. Sci. 2013; 5: 465–8.

42 Xiao JZ, Kondo S, Yanagisawa N, et al. Effect of Probiotic Bifidobacterium longum BBS36 in relieving clinical symptoms and modulating plasma cytokine levels of japanese cedar pollinosis during the pollen season. A randomized double-blind, placebo-controlled trial. 2006.

43 Wassenberg J, Nutten S, Audran R, et al. Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis. Clin Exp Allergy 2011; 41: 565–73.

44 Kang M-G, Han S-W, Kang H-R, Hong S-J, Kim D-H, Choi J-H. Probiotic NVP-1703 Alleviates Allergic Rhinitis by Inducing IL-10 Expression: A Four-week Clinical Trial. Nutrients 2020; 12: 1427.

45 Singh A, Hacini-Rachinel F, Gosoniu ML, 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: 161–7.

46 Anvari S, Miller J, Yeh CY, Davis CM. IgE-Mediated Food Allergy. Clin Rev Allergy Immunol 2019; 57: 244–60.

47 Toh ZQ, Anzela A, Tang MLK, Licciardi P V. Probiotic therapy as a novel approach for allergic disease. Front Pharmacol 2012; 3 SEP. DOI:10.3389/fphar.2012.00171.

48 Robertson RC, Manges AR, Finlay BB, Prendergast AJ. The Human Microbiome and Child Growth – First 1000 Days and Beyond. Trends Microbiol. 2019; 27: 131–47.

49 Tibbs TN, Lopez LR, Arthur JC. The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging. Microb. Cell. 2019; 6: 324–34.

50 Dominguez-Bello MG, Godoy-Vitorino F, Knight R, Blaser MJ. Role of the microbiome in human development. Gut 2019; 68: 1108–14.