Yeast
Summary
Saccharomyces cerevisiae is a unicellular fungus known as baker's yeast or brewer's yeast. It is an edible budding yeast that is considered safe and therefore possesses various applications in food, beverage, biofuels, and pharmaceutical industry. It occurs naturally in plants and soil. S. cerevisiae is round-to-oval in shape and reproduces through a budding mechanism. Different strains of S. cerevisiae are found in various parts of the world. Allergic reactions due to baker's yeast are rarely reported. S. cerevisiae contains both inhalant and food allergens. It may induce allergic respiratory symptoms, most predominantly baker’s asthma, and allergic rhinitis and also hypersensitivity pneumonitis on inhalation. Moreover, atopic dermatitis and anaphylaxis on ingestion of yeast have been rarely reported in baker’s yeast sensitized individuals. Additionally, anti- S. cerevisiae antibodies (ASCA) are considered as biomarkers for patients suffering from irritable bowel disease. The major allergen identified in S. cerevisiae is Sac c enolase, which is a cross-reactive allergen. Cross-reactivity has been observed between other yeast and mold species. S. cerevisiae allergic patients are advised to avoid yeast inhalation or eliminate yeast ingestion and preferably to have yeast-free diet.
Epidemiology
Worldwide distribution
The pervasiveness of allergenic sensitization to fungi is not known clearly; however, few studies claimed it to be around 6% in the general population.
Prevalence of type I allergy caused by Saccharomyces is found to be 1.4% in the general population and 7.4% in atopic individuals.
A study by Marszalska et al. (2001) aimed to show enolase (a major allergen from S. cerevisiae)-mediated immediate allergic response in patients with inhalant allergy sensitized to Candida albicans (C. albicans) extract. The study included a total of 70 patients divided into three groups (group I: 20 atopic patients with respiratory allergy sensitized to C. albicans and inhalant allergens such as mite, feather, pollens, group II: 30 patients with respiratory allergy, showing positive and negative skin tests to inhalant allergens and C. albicans respectively, group III: 20 nonatopic, healthy individuals) and detected 95% of group I patients and 10% of group II patients showing positive skin reactions to S. cerevisiae enolase.
Another study by Savolainen et al. (1993) in Finland evaluated the sensitizing capacity of S. cerevisiae in 449 allergic subjects [226 with atopic dermatitis (AD), 50 with allergic rhinitis (AR) and/or asthma, and 173 nonatopic controls], through skin prick tests (SPT). Out of 449 patients, 20% (92 patients; 85 with AD 4 with AR/asthma, and 3 nonatopic controls) showed positive SPT reaction to S. cerevisiae.
Route Of Exposure
Main
Inhalation of S. cerevisiae aeroallergen is considered as the primary route of exposure.
Secondary
Another route of exposure to S. cerevisiae allergens is via ingestion.
Clinical Relevance
In sensitized individuals, exposure to S. cerevisiae may lead to respiratory symptoms, such as asthma, particularly baker's asthma, AR, and hypersensitivity pneumonitis. Additionally, skin symptoms such as AD and chronic urticaria are reported to be caused by S. cerevisiae. Anaphylaxis is rarely reported due to baker’s yeast hypersensitivity.
Allergic rhinitis
Inhalation of fungal allergens may trigger rhinitis in sensitized individuals. A study by Baldo et al. (1988) evaluated 47 fungal allergic (inhalant allergen) patients for allergic sensitivity to bakers' yeast. As per the result, 32 patients were radioallergosorbant test (RAST)-positive to bakers' yeast antigens. Enolase was the major allergen identified from S. cerevisiae.
Asthma
Baker's asthma is a well-known occupational allergic condition that occurs due to hypersensitivity to different antigens, such as flour, bran, yeast, baking additives, storage mites, etc. Moreover, other ingredients found in baked goods and pastry have been reported to cause allergy. Baker’s yeast (S. cerevisae) is a bakery ingredient that has been reported to be associated with some isolated cases of baker’s asthma. However, sensitization to this baker’s yeast allergen is not common compared to the cereal flours or enzymes. Nonetheless, this needs to be considered in the clinical setting when no sensitization is observed for common bakery allergens.
Hernandez et al. (1996) presented a case of a 48-year-old bakery worker (nonsmoker) with recurrent episodes of hydrorrhea, sneezing, nasal obstruction, wheezing, spasmodic cough, and dyspnea within 1 or 2 hrs, following the start of his work. The symptoms at first were mild and worsened with time. However, his symptoms appeared to improve on holidays. The causative agent was found to be S. cerevisiae dry powder that created a dusty environment and possibly triggered occupational asthmatic condition in the baker (baker's asthma).
Another case of baker's yeast true allergy in a boy with a history of mite-allergy and AD was reported by Pajno et al. (2005). The boy experienced generalized urticaria and asthma after eating pizza and bread (only fresh oven-baked). On investigation, he was found to be sensitized only to baker's yeast (S. cerevisiae), and the prick-by-prick procedure observed the severe systemic reaction. The severity of allergic reactions and urticaria subsided in 2 years. However, after the consumption of freshly baked and yeast-containing products, the patient still had a cough. The study suggested that continuous exposure to S. cerevisiae may result in immunotolerance and gradual reduction of allergic symptoms.
Atopic Dermatitis
S. cerevisiae exhibited a significant association between positive SPT and AD.
A study on 449 allergic patients reported that about 50% suffered from AD, 11% from AR and/or asthma, and 38.5% were nonatopic individuals. The study detected that AD patients with chronic dermatitis had considerably higher SPT reactions to S. cerevisiae than AR/ asthma or nonatopic controls. Skin-specific IgE was detected for brewer's yeast in 94% of patients with severe AD, 76% with moderate AD, and 25% with mild AD or no history of AD. This indicated that the brewer's yeast had caused sensitization.
Other diseases
Invasive infection
Saccharomyces organisms are reported as a prime contributor to invasive infections, particularly in immunocompromised or severely ill patients. S. cerevisiae has been frequently isolated from the vaginal flora of 0.9% – 5.8% of women. Moreover, S. cerevisiae is thought to cause symptoms similar to Candida vaginitis in 0.4% of patients. S. cerevisiae was also isolated from the throat (16%), stool (23%), urine (10%), and perineum (20%) of patients with hematologic disease. Similarly, a comprehensive review of published reports on invasive Saccharomyces infection by Angoulvant et al. (2005) detected 92 confirmed Saccharomyces invasive infection cases, which was clinically similar to invasive candidiasis. In most patients, the causative organism of fungemias was S. boulardii (51.3%), a subtype of S. cerevisiae.
Irritable bowel disease (IBD) and S. cerevisiae autoantibodies
Anti- S. cerevisiae antibody (ASCA), an antiglycan antibody against the cell wall surface of baker’s yeast, is commonly detected in the sera of patients with Crohn’s disease (CD) and ulcerative colitis (UC), the subtypes of irritable bowel disease (IBD). The bakery workers commonly develop CD (also called baker’s disease), and a diet low in baker’s yeast has been found to lower CD. This indicates the involvement of ASCA in CD pathogenesis. Although the exact cause of ASCA generation is not clear, it has been postulated that higher permeability in the small bowel of CD patients may result in higher exposure of reactive immune cells towards yeast antigens (typically found in the intestinal microbiota), leading to CD. In CD patients, an increased level of IgG and IgA ASCA has been reported. In fact, IgG ASCA is considered as a biomarker for IBD (positive rate 60-70% in CD patients and 10-15% in UC patients).
Prevention And Therapy
Prevention strategies
Avoidance
Patients hypersensitive to S. cerevisiae should avoid inhalation of yeast or eliminate the ingestion of yeast in their diet and prefer a yeast-free diet.
Cross-Reactivity
Enolase is considered to be a cross-reactive allergen among various fungal species, including S. cerevisiae, C. herbarum, A. alternata, C. albicans, etc. Allergens from S. cerevisiae, such as Sac c Cyp, Sac s MnSOD, are also reported to cross-react between different allergenic molecules of other fungal phyla. HSP90 (Heat shock protein) from S. cerevisiae is homologous to A. fumigatus allergen Asp f 12, an HSP90 protein. C. albicans and S. cerevisiae are cross-reactive due to homology among allergens; however, specific common allergens are yet to be identified.
Ingestion of yeast may induce allergy in mold-allergic patients. This was observed in a case study. A patient (29-year-old American woman) with a respiratory IgE sensitization to fungi (such as Alternaria alternata, Cladosporium herbarum, Aspergillus fumigatus, and Penicillium notatum) and S. cerevisiae was reported to develop several anaphylactic reactions after eating pasta along with yeast sauces consisting of cross-reacting fungal allergens. The patient was able to eat bakery products but developed allergic reactions for food or sauces with yeast flavoring. Moreover, increased exposure to mold aeroallergens leads to higher sensitivity towards the ingested yeast species. This indicated that yeast is likely to be an ingestive allergen in fungi sensitized persons.
Cross-reactivity was found among bakers' yeast, enolase from bakers' yeast, and C. albicans.
References
- Levetin E, Horner WE, Scott JA, Environmental Allergens W. Taxonomy of Allergenic Fungi. J Allergy Clin Immunol Pract. 2016;4(3):375-85 e1.
- Parapouli M, Vasileiadis A, Afendra AS, Hatziloukas E. Saccharomyces cerevisiae and its industrial applications. AIMS Microbiol. 2020;6(1):1-31.
- Belda I, Ruiz J, Santos A, Van Wyk N, Pretorius IS. Saccharomyces cerevisiae. Trends Genet. 2019;35(12):956-7.
- Salari R, Salari R. Investigation of the Best Saccharomyces cerevisiae Growth Condition. Electron Physician. 2017;9(1):3592-7.
- Horner WE, Armstrong M, El-Dahr J, McCants M, Reese G, Kobernick AK, et al. Prevalence of IgE reactivities in mold-allergic subjects to commercially available fungal enzymes. Allergy Asthma Proc. 2008;29(6):629-35.
- Simon-Nobbe B, Denk U, Poll V, Rid R, Breitenbach M. The spectrum of fungal allergy. Int Arch Allergy Immunol. 2008;145(1):58-86.
- Nittner-Marszalska M, Wójcicka-Kustrzeba I, Bogacka E, Patkowski J, Dobek R. Skin prick test response to enzyme enolase of the baker's yeast (Saccharomyces cerevisiae) in diagnosis of respiratory allergy. Med Sci Monit. 2001;7(1):121-4.
- Kortekangas-Savolainen O, Lammintausta K, Kalimo K. Skin prick test reactions to brewer's yeast (Saccharomyces cerevisiae) in adult atopic dermatitis patients. Allergy. 1993;48(3):147-50.
- Liti G. The fascinating and secret wild life of the budding yeast S. cerevisiae. Elife. 2015;4.
- Boynton PJ, Greig D. The ecology and evolution of non-domesticated Saccharomyces species. Yeast. 2014;31(12):449-62.
- Pajno GB, Passalacqua G, Salpietro C, Vita D, Caminiti L, Barberio G. Looking for immunotolerance: a case of allergy to baker's yeast (Saccharomyces cerevisiae). Eur Ann Allergy Clin Immunol. 2005;37(7):271-2.
- Airola K, Petman L, Makinen-Kiljunen S. Clustered sensitivity to fungi: anaphylactic reactions caused by ingestive allergy to yeasts. Ann Allergy Asthma Immunol. 2006;97(3):294-7.
- Belchi-Hernandez J, Mora-Gonzalez A, Iniesta-Perez J. Baker's asthma caused by Saccharomyces cerevisiae in dry powder form. J Allergy Clin Immunol. 1996;97(1 Pt 1):131-4.
- Quirce S, Diaz-Perales A. Diagnosis and management of grain-induced asthma. Allergy Asthma Immunol Res. 2013;5(6):348-56.
- Brisman J. Baker's asthma. Occupational and Environmental Medicine. 2002;59(7):498-502.
- Baldo BA, Baker RS. Inhalant allergies to fungi: reactions to bakers' yeast (Saccharomyces cerevisiae) and identification of bakers' yeast enolase as an important allergen. Int Arch Allergy Appl Immunol. 1988;86(2):201-8.
- Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis. 2005;41(11):1559-68.
- Mitsuyama K, Niwa M, Takedatsu H, Yamasaki H, Kuwaki K, Yoshioka S, et al. Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol. 2016;22(3):1304-10.
- Israeli E, Grotto I, Gilburd B, Balicer R, Goldin E, Wiik A, et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005;54(9):1232-6.
- Kortekangas-Savolainen O, Savolainen J, Lantto R, Kalimo K. Immediate hypersensitivity to bakery, brewery and wine products in yeast-sensitive atopic dermatitis patients. Clin Exp Allergy. 1994;24(9):836-42.
- WHO/IUIS. Saccharomyces cerevisiae 2020 [December 24, 2020]. Available from: http://www.allergen.org/search.php?allergenname=&allergensource=Saccharomyces+cerevisiae+&TaxSource=&TaxOrder=&foodallerg=all&bioname=.
- Rhyner C, Daigle I, Crameri R. Auto-reactive IgE responses to acidic ribosomal P(2) protein in systemic lupus erythematosus. Allergy. 2011;66(8):1127-9.
- Le LQ, Mahler V, Scheurer S, Foetisch K, Braun Y, Weigand D, et al. Yeast profilin complements profilin deficiency in transgenic tomato fruits and allows development of hypoallergenic tomato fruits. FASEB J. 2010;24(12):4939-47.
- Nenoff P, Müller B, Sander U, Kunze G, Bröker M, Haustein UF. IgG and IgE immune response against the surface glycoprotein gp200 of Saccharomyces cerevisiae in patients with atopic dermatitis. Mycopathologia. 2001;152(1):15-21.
- Koivikko A, Kalimo K, Nieminen E, Savolainen J, Viljanen M, Viander M. Allergenic cross-reactivity of yeasts. Allergy. 1988;43(3):192-200.
- Popescu FD. Cross-reactivity between aeroallergens and food allergens. World J Methodol. 2015;5(2):31-50.
