f45 Yeast

Allergens within Food of Plant Origin

Print Print icon Tell a friend Tell a friend icon
  • Latin name: Saccharomyces cerevisiae
  • Family: Saccharomycetaceae
  • Common names: Yeast, Baker's yeast, Brewer’s yeast
Food
A food, which may result in allergy symptoms in sensitised individuals.

Allergen Exposure

Geographical distribution
Fungi are eukaryotic unicellular or multicellular organisms with absorptive nutrition. They have been classified traditionally as members of the Plant kingdom. More recently, a separate kingdom, Fungi, was established for them, although species historically considered fungi are currently distributed among several kingdoms (1). Yeasts such as Saccharomyces cerevisiae are single-celled fungi that that multiply by budding, or in some cases by division (fission), although some yeasts such as Candida albicans may grow as simple irregular filaments (mycelia).
 
The genus Saccharomyces includes several species, the most well-known being Saccharomyces cerevisiae. Colonies of Saccharomyces grow rapidly and mature in 3 days. They are flat, smooth, moist, glistening or dull, and cream to tannish. The inability to utilise nitrate and the ability to ferment various carbohydrates are typical characteristics of Saccharomyces.
 
Saccharomyces cerevisiae is the most important Yeast in the world, and has been very useful for humans for millennia. It is commonly known as Baker’s yeast or Brewer’s yeast. No allergenic difference has been noted between these. The same species is used for both processes, but different strains and sub-strains have been adapted for and within either. To gain energy from the breakdown of carbohydrates, the yeast ferments sugars, giving off carbon dioxide (CO2) and alcohol (ethanol). The CO2 is trapped as tiny bubbles in the dough, which consequently rises. In beer and wine-making, the alcohol is the important product, although the carbon dioxide may be used in beer and champagne.
 
Environment
Fungi grow almost everywhere, even as lichens inside Antarctic rocks. Airborne spores are usually present in outdoor air throughout the year in high numbers and frequently exceed pollen concentrations by 100-to 1,000-fold, depending on environmental factors such as water and nutrient availability, temperature, and wind. Most fungi commonly considered allergenic, such as Alternaria, display a seasonal spore release pattern, but this is not as well defined as it is for pollens. Airborne spores are frequently dense enough to present a substantial antigen load. Generally, indoor fungi are a mixture of those from outdoors and from indoors. Aspergillus spp. and Penicillium spp. are less common outdoors and are generally considered the major indoor fungi. Yeast contamination of cold-air home humidifiers has been documented (1).
 
Torula, listed on some processed and smoked foods, is also a Yeast, and may be called nutritional Yeast (though it should not be confused with Baker’s or Brewer’s yeast). Yeast may be a hidden allergen in mayonnaise, ketchup, and other processed foods, particularly those enriched with B-complex vitamins. Yeast-derived products include flavour enhancers, flavourants (especially in smoke-flavoured meats), enzymes (e.g., to reduce lactose in milk), and ingredients in vitamin and mineral supplements, other pharmaceuticals, and cosmetics.
In some markets, particularly Australia and the UK, specific human foodstuffs (Vegemite and Marmite) have been developed from Brewer's yeast.
 
Unexpected exposure
The name Saccharomyces boullardii, for an organism now used in the treatment of intestinal disorders such as antibiotic-associated diarrhoea, is considered to be a synonym for a particular strain of Saccharomyces cerevisiae (2).
 
Allergens
Immunoblotting studies have demonstrated that there are at least 5 IgE-binding bands in S. cerevisiae (3). The most important allergens have been shown to be of around 32 kDa, 45 kDa and 48 kDa in size. The 32 kDa and 48 kDa allergens appear to be unstable: both lose their IgE-binding capacity, even when the extracts are stored with 50% glycerol at +6 degrees C. The 45 kDa allergen is, on the other hand, quite stable after storage for 9 months at +6 degrees C. This has implications for commercially available S. cerevisiae extracts in solution; in the study, 2 of such extracts had little allergenic potency, while a freeze-dried extract stored for 8 years showed good allergenic potency (4).
 
Allergens characterised:

Sac c Enolase, a 46-51 kDa protein, an enzyme, and the most important allergen (3, 5-10).
 
Sac c CyP, a cyclophilin (11).
 
A heat-stable and soluble glycoprotein, gp200, with a molecular weight of 200 kDa, has been isolated and is part of the cell wall of S. cerevisiae. An association has been shown between IgA and IgG against gp200 and inflammation in Crohn's disease (12, 13). Further studies will elucidate the exact role that this proteins plays in this disease.

Potential Cross-Reactivity

Allergenic cross-reactivity has been demonstrated among Baker's yeast, Baker's yeast enolase and Candida albicans (5). However, the cross-reactivity is complex. In a study of sera of 54 patients with serum-specific IgE to C. albicans, IgE antibody to the C. albicans enolase was found in 20 sera (37%). Simultaneous IgE binding to S. cerevisiae enolase was observed in only 4 out of 20 sera reacting to C. albicans enolase. These results suggest that C. albicans enolase shares some cross-reacting epitopes with S. cerevisiae enolase, representing minor components of C. albicans enolase but dominant segments of S. cerevisiae enolase (10).
 
Similarly, a study reports that the enolase from Rhodotorula mucilaginosa shares high sequence identity with enolase allergens from Candida albicans (85%), Saccharomyces cerevisiae (76%), Penicillium citrinum (76%), Aspergillus fumigatus (76%), Cladosporium herbarum (76.5%), and Alternaria alternata (74%). Although enolases are highly conserved allergens among different fungal species, most of the allergic patients examined in this study differed in their IgE reactivity to the 5 different fungal enolases tested (6).
 
The vacuolar serine protease from Penicillium citrinum, Pen c 2, has been shown to share a high sequence similarity with vacuolar serine proteases from Aspergillus niger and Saccharomyces cerevisiae (14). The clinical significance of this has yet to be determined.
 
Studies have also shown that Candida albicans cross-reacts with Saccharomyces cerevisiae or Pityrosporum ovale at the IgE level, and that the C. albicans mannoproteins may be responsible for the cross-reactivity among these Yeast species at this level (15). In a study in patients with atopic dermatitis, IgE binding to S. cerevisiae mannan was completely inhibited by C. albicans mannan preparations, whereas reciprocal inhibition was not complete. The authors concluded that these results indicated that in atopic dermatitis, simultaneous IgE response to Yeast polysaccharides occurs, that the major sensitiser is C. albicans, and that IgE antibodies against S. cerevisiae mannan were cross-reacting (16).
 
In a study evaluating Candida albicans allergens, IgE antibodies of 57 allergic patients were examined for antibody to C. albicans. A number of allergens were detected, of which the 175-, 125-, 46-, 43-, and 37-kDa allergens reacted most frequently with the patient sera. Parts of the sequences of the 46-, 43-, and 37-kDa antigens were shown to have significant levels of homology with S. cerevisiae glycolytic enzyme enolase, phosphoglycerate kinase, and aldolase, respectively. However, S. cerevisiae enolase and phosphoglycerate kinase did not cross-react with IgE of patient sera, suggesting that IgE antibodies against only small parts of their epitopes are elevated in the allergic patients. The authors concluded that since enolase is reported to be a major antigen for systemic candidiasis, this enzyme may be the immunodominant protein in both allergies and fungal infections (17).

Clinical Experience

IgE-mediated reactions
S. cerevisiae may induce symptoms of allergy, including allergic rhinitis, asthma, and atopic dermatitis, in sensitised individuals (3, 5, 18-19). Hypersensitivity pneumonitis has been reported (20).
 
S. cerevisiae has been reported to be a significant cause of Bakers’ Asthma, a well-defined disease which can be caused by various antigens: flours and bran, Yeast, baking additives, saprophytic molds, and Storage mites. Hypersensitivity to flour is a significant cause of Baker’s asthma (21), but in recent years many more substances used in baked goods and pastry have been reported as causes of allergy, including S. cerevisiae. Nevertheless, occupational asthma caused by this Yeast is uncommon in bakers, despite the frequent use of this Yeast. And although it is always present in the baking industry, it does not easily affect the airways and rarely sensitises workers.
 
Importantly, S. cerevisiae is used in bakeries either as a conventional wet Yeast or in a dry powder form. Conventional wet Yeast is always used in a cold-water solution, which works against the formation of a dusty environment. In contrast, flours and baking additives always form dusty environments. As S. cerevisiae can now be preserved in dehydrated form and does not require special storage conditions, a dusty environment may be created, which may result in increased reports of sensitisation to this Yeast. For example, Bakers’ asthma was reported in a 48-year-old man who experienced repeated episodes of rhinorrhoea, sneezing, nasal obstruction, wheezing, spasmodic cough, and dyspnoea, with onset 1 to 2 hours after starting work. Serum-specific IgE to S. cerevisiae was found, and a bronchial challenge was positive (22).
 
In a study of 178 symptomatic bakers and pastry workers from small businesses in western France, 65 were evaluated for common causes of sensitisation. Twelve (18%) workers were shown to have skin-specific IgE to at least 1 common or occupational allergen: 36 (57%) were sensitisted to Dermatophagoides pteronyssinus mite, 23 (35%) to Alpha amylase, 17 (26%) to Wheat flour, 16 (25%) to S. cerevisiae, and 15 (24%) to Ephestia (23).
 
S. cerevisiae, present as an aeroallergen, may result in sensitisation in non-occupational settings also. In a study of 47 subjects with respiratory allergy and sensitisation to fungi who were tested for sensitivity to Bakers' yeast, 35 were found to have skin-specific IgE to this Yeast, and serum-specific IgE to S. cerevisiae was found in the serum of 32 subjects (5).
 
S. cerevisiae enolase is a major allergen, and has been reported to be a significant allergen in subjects who have respiratory allergy and show positive skin-specific IgE tests to Candida albicans and other fungi. This is not surprising, as the enolase allergen may function as a panallergen; other fungi will need to be considered in the evaluation of these patients (8).
 
S. cerevisiae has also been reported to exacerbate atopic dermatitis (24). A study evaluated the sensitising capacity of S. cerevisiae in 449 allergic subjects, through skin-specific IgE testing. The study group included 226 patients with atopic dermatitis, 50 patients with allergic rhinitis and/or asthma, and 173 nonatopic controls. Skin-specific IgE was detected to this Yeast in 94% of patients with severe atopic dermatitis, in 76% with moderate atopic dermatitis, and in 25% with mild atopic dermatitis or no history of AD (25).
 
S. cerevisiae usually acts as an allergen only by the inhalatory route. A study described Baker's yeast allergy in a 6-year-old boy, who experience generalized urticaria and asthma after eating pizza and bread, but only when fresh from the oven. Sensitization to S. cerevisiae was confirmed, with a severe systemic reaction occurring during the skin specific IgE test procedure. In the subsequent two years without any dietary restriction, the severity of symptoms progressively reduced and the occurrence of urticaria resolved. Only symptoms of cough persisted, invariably after eating just-baked and yeast-containing foods. Symptoms did not occur if bread, pizza and cakes were ingested more than one hour after preparation. The authors speculate that the continuous exposure to S. cerevisiae in foods may have lead to an immunotolerance with progressive reduction of symptoms. Why the allergens are active only in ready-baked foods could not be unexplained (26).
 
Whether patients with hypersensitivity to S. cerevisiae should avoid ingesting this Yeast in their diet is controversial. In a study where samples of beer, aged red wine, young white wine, sparkling wine and extracts of fresh Wheat bread and dried Rye bread were analysed to find whether they contained Baker's yeast allergens, beer, bread, red wine and sparkling wine extracts were found to be positive. White wine extract caused adverse reactions in 4 of 6 patients with atopic dermatitis, in 5 of 7 symptom-free patients with atopic dermatitis, and in 2 of the 24 controls. No Baker's yeast antigen could be detected in brewery and bakery products with IgE-immunoblotting tests, even in the excessively concentrated extracts. The authors concluded that IgE-mediated allergy to Baker's yeast alone should not lead to avoidance of bakery, brewery and wine products (24).
 
However, contrary to this study is a report that investigated a high incidence of chronic urticaria among female patients, and postulated that as it is frequently difficult to identify the aetiologic factors, the possible role of Candida albicans and other Yeasts in foods and beverages may be relevant. After 1-2 weeks of an elimination diet, each patient was challenged with Yeast-containing foods (bread, buns, sausages, beer, wines, Grapes, cheese, vinegar, Tomato catsup). Twenty-five patients (71%) of the group sensitised to Candida albicans reported the reappearance of urticaria, and twenty patients (69%) sensitised to Saccharomyces had a positive challenge test (27).
 
The heat-stable and soluble glycoprotein gp200 (molecular weight 200 kDa) is part of the cell wall of S. cerevisiae, and an association was shown between IgA and IgG against gp200 and inflammation in Crohn's disease (12). The role of this protein will require further clarification. In a study, specific IgE against S. cerevisiae was detected in approximately 73% of patients suffering from severe atopic dermatitis, and in 68% against Candida albicans. Anti-gp200 IgE was found in 55% of healthy individuals, in 67% of individuals with atopic predisposition without eczema, in 63% of the patients with mild atopic dermatitis, and in 86% of patients with severe atopic dermatitis, respectively. The study concluded that occurrence of specific IgE against S. cerevisiae could not be explained by cross-reactivity, e.g., against Candida albicans allergens, and that further investigations with recombinant gp200 will elucidate the role of this glycoprotein both in atopic dermatitis and Crohn’s disease (13).
 
Other reactions
Fungi cause a number of infectious diseases. These range from superficial skin lesions primarily of cosmetic concern to potentially fatal systemic mycoses.
 
Reports have indicated that S. cerevisiae may result in allergic bronchopulmonary disease such as hypersensitivity pneumonitis. A 58-year-old dairy farmer, who had cough, fever and dyspnoea following repeated exposure to moldy silage in a silo, was shown to have hypersensitivity pneumonitis. Samplings from the silage revealed a severe growth of S. cerevisiae, and serum-precipitating antibody was positive for an extract of S. cerevisiae (20). Similarly, allergic bronchopulmonary fungal disease was reported in a patient with dry cough, low-grade fever, and focal patchy shadow of pulmonary infiltrates following exposure to this Yeast (28).
 
A 22-year-old woman developed recurrent episodes of fever, cough and dyspnoea after repeated exposure to a misting fountain at home. A diagnosis of extrinsic allergic alveolitis was made by detection of serum antibodies against the fountain water, by culture of Bacillus subtilis, Mucor racemosus, Mucor mucedo, and Saccharomyces cerevisiae from the water, and by detection of specific IgG antibodies against Bacillus subtilis and the Mucores. An inhalation challenge with the misting fountain resulted in a positive reaction. The authors suggest that because this humidifier system has recently become widespread in homes, clinicians should be aware of this specific type of extrinsic allergic alveolitis, which they call "misting fountain alveolitis" (29).
 
To assess whether dietary antigens play a role in inflammatory bowel disease, 26 monozygotic twin pairs with inflammatory bowel disease and 52 healthy controls were investigated for serum antibodies (IgA, IgG, IgM) against ovalbumin, betalactoglobulin, gliadin, whole Yeast (S. cerevisiae) and Yeast cell wall mannan. The study’s results suggested that Yeast cell wall material (mannan), or some antigen rich in mannose and cross-reacting with mannan, may play an aetiological role in Crohn's disease, but not in ulcerative colitis (30).
 
A study reported over 2 decades ago that 33% of a group of patients with migraine were hypersensitive to Yeast (31).
 
Compiled by Dr Harris Steinman, harris@zingsolutions.com.

References:

    1. Horner WE, Helbling A, Salvaggio JE, Lehrer SB. Fungal allergens.. Clin Microbiol Rev 1995 ;8(2):161-79
    2. Hogenauer, C., H. F. Hammer, G. J. Krejs, and E. C. Reisinger. 1998. Mechanisms and management of antibiotic-associated diarrhea. Clin Infect Dis. 27:702-710.
    3. Savolainen J, Kortekangas-Savolainen O, Nermes M, Viander M, et al. IgE, IgA, and IgG responses to common yeasts in atopic patients. Allergy 1998;53(5):506-512
    4. Kortekangas-Savolainen O, Einarsson R. Thermal and storage stability of Saccharomyces cerevisiae (baker's yeast) allergens. Clin Exp Allergy 1994;24(3):257-62
    5. 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;86:201-8
    6. Chang CY, Chou H, Tam MF, Tang RB, Lai HY, Shen HD. Characterization of enolase allergen from Rhodotorula mucilaginosa. J Biomed Sci 2002;9(6 Pt 2):645-55
    7. Mason AB, Buckley HR, Gorman JA. Molecular cloning and characterization of the Candida albicans enolase gene. J Bacteriol 1993;175(9):2632-9
    8. Nittner-Marszalska M, Wojcicka-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):121-124
    9. Simon-Nobbe B, Probst G, Kajava AV, Oberkofler H, Susani M, Crameri R, et al. IgE-binding epitopes of enolases, a class of highly conserved fungal allergens. J Allergy Clin Immunol 2000;106(5):887-895
    10. Ito K, Ishiguro A, Kanbe T, Tanaka K, Torii S. Detection of IgE antibody against Candida albicans enolase and its crossreactivity to Saccharomyces cerevisiae enolase. Clin Exp Allergy 1995;25(6):522-8
    11. Roy D, Ghosh D, Gupta-Bhattacharya S. Homology modeling of allergenic cyclophilins: IgE-binding site and structural basis of cross-reactivity. Biochem Biophys Res Commun 2003;307(2):422-9
    12. van den Bogaerde J, Kamm MA, Knight SC. Immune sensitization to food, yeast and bacteria in Crohn's disease. Aliment Pharmacol Ther 2001;15(10):1647-53
    13. Nenoff P, Muller B, Sander U, Kunze G, Broker 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
    14. Chow LP, Su NY, Yu CJ, Chiang BL, Shen HD. Identification and expression of Pen c 2, a novel allergen from Penicillium citrinum. Biochem J 1999;341 (Pt 1):51-9
    15. Kanbe T, Utsunomiya K, Ishiguro A. A crossreactivity at the immunoglobulin E level of the cell wall mannoproteins of Candida albicans with other pathogenic Candida and airborne yeast species. Clin Exp Allergy 1997;27(12):1449-57
    16. Nermes M, Savolainen J, Kortekangas-Savolainen O. Nitrocellulose-RAST analysis of allergenic cross-reactivity of Candida albicans and Saccharomyces cerevisiae mannans. Int Arch Allergy Immunol 1995;106(2):118-23
    17. Ishiguro, A., M. Homma, S. Torii, and K. Tanaka. Identification of Candida albicans antigens reactive with immunoglobulin E antibody of human sera. Infect Immun 1992;60:1550-1557
    18. Mari A, Schneider P, Wally V, Breitenbach M, Simon-Nobbe B. Sensitization to fungi: epidemiology, comparative skin tests, and IgE reactivity of fungal extracts. Clin Exp Allergy 2003 Oct;33(10):1429-38
    19. MacKechnie HLN Clinical spectrum of yeast hypersensitivity. Ann Allergy 1978;39:334-338
    20. Yamamoto Y, Osanai S, Fujiuchi S, Akiba Y, Honda H, Nakano H, Ohsaki Y, Kikuchi K. Saccharomyces-induced hypersensitivity pneumonitis in a dairy farmer: a case report. [Japanese] Nihon Kokyuki Gakkai Zasshi 2002;40(6):484-8
    21. Armentia A, Martin-Santos JM, Quintero A, Fernandez A, Barber D. Bakers’ asthma: prevalence and evaluation of immunotherapy with a wheat flour extract. Ann Allergy 1990;65:265-72.
    22. 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
    23. Bataille A, Anton M, Mollat F, Bobe M, Bonneau C, Caramaniam MN, Geraut C, Dupas D. Respiratory allergies among symptomatic bakers and pastry cooks: initial results of a prevalence study. [French] Allerg Immunol (Paris) 1995;27(1):7-10
    24. Kortekangas-Savolainen O, Savolainen J, et al. Immediate hypersensitivity to bakery, brewery and wine products in yeast-sensitive atopic dermatitis patients. Clin Exp Allergy 1994;24(9):836-842
    25. 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
    26. 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). Allerg Immunol (Paris) 2005;37(7):271-2.
    27. Serrano H. Hypersensitivity to "Candida albicans" and other fungi in patients with chronic urticaria [Spanish]. Allergol Immunopathol (Madr) 1975;3(5):289-298
    28. Ogawa H, Fujimura M, Tofuku Y. Allergic bronchopulmonary fungal disease caused by Saccharomyces cerevisiae. J Asthma 2004;41(2):223-8
    29. Koschel D, Sennekamp J, Schurz C, Muller-Wening D. Misting-fountain-alveolitis. [German] Pneumologie Sep;2004:58(9):666-9
    30. Lindberg E, Magnusson KE, Tysk C, Jarnerot G. Antibody (IgG, IgA, and IgM) to baker's yeast (Saccharomyces cerevisiae), yeast mannan, gliadin, ovalbumin and betalactoglobulin in monozygotic twins with inflammatory bowel disease. Gut 1992;33(7):909-13
    31. Grant ECG. Food allergies and migraine. Lancet 1979;1:966-968

2006



Further Reading