Latin name: Saccharomyces cerevisiae
Common names: Yeast, Baker's yeast, Brewer’s yeast
A food, which may result in allergy symptoms in sensitised individuals.
Fungi are eukaryotic unicellular or multicellular organisms with absorptive nutrition. Traditionally, they have been classified as members of the plant kingdom. More recently, a separate kingdom – Fungi – was established for them, although species historically considered fungi are currently distributed over 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, cream to tannish, and may be glistening or dull. 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 to 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 both. 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 in beer and champagne the carbon dioxide may also be used.
Fungi grow almost everywhere, even as lichens inside Antarctic rocks. Airborne spores are usually present in outdoor air in high numbers throughout the year, 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 the outdoors and those 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 the ingredient lists of 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.
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)
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. On the other hand, the 45 kDa allergen is 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 this type of extract had little allergenic potency, while a freeze-dried extract stored for 8 years showed good allergenic potency. (4)
The following allergens have been characterized:
Sac c Enolase, a 46-51 kDa protein, an enzyme, and the most important allergen. (3, 5, 6, 7, 8, 9, 10)
Sac c CyP, a cyclophilin. (11, 12)
Sac c MnSOD, a manganese superoxide dismutase. (13, 14)
Sac c HSP, also known as Hsp60, a heat shock protein. (15)
Sac c Carboxypeptidase, a serine carboxypeptidase. (16)
Sac c Glucosidase, a glucosidase. (15)
Sac c Invertase, a fructofuranosidase. (16)
Sac c P2, also known as Ribosomal Protein P2. (17)
Sac c Profilin, a profilin. (18)
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. (19, 20) Further studies will elucidate the exact role that this protein plays in this disease.
Sac c Profilin was shown to share a 32.6% amino acid sequence identity with Lyc e 1 from tomato, but displayed low IgE-binding capacity and allergenic potency. Among 16 tomato-allergic patients preselected for sensitisation to Lyc e 1, none showed significant reactivity to yeast profilin. (18)
Allergenic cross-reactivity has been demonstrated between 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. (21) 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. (22) 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. (23)
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 the 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. (24)
Pen c 24 from P. citrinum has a 53% similarly with elongation factor 1-beta (EF-1beta) from S. cerevisiae. (25) The clinical significance of this was not examined.
a. IgE-mediated reactions
S. cerevisiae may induce symptoms of allergy, including allergic rhinitis, asthma, and atopic dermatitis, in sensitised individuals. (3, 5, 26, 27) Hypersensitivity pneumonitis has been reported. (28)
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 moulds and storage mites. Hypersensitivity to flour is a significant cause of Baker’s Asthma, (29) 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. (30)
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 sensitised to Dermatophagoides pteronyssinus mite, 23 (35%) to Alpha amylase, 17 (26%) to wheat flour, 16 (25%) to S. cerevisiae, and 15 (24%) to Ephestia. (31)
S. cerevisiae, present as an aeroallergen, may also result in sensitisation in non-occupational settings. 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)
A study evaluated IgE antibody reactivity by RAST to commercially available fungal enzymes in sera from 20 subjects with symptoms of respiratory allergies, and skin test reactivity to 2 or more fungal allergens. The most reactive fungal enzymes were invertase (Saccharomyces cerevisiae), cellulase (Trichoderma viride), and glucosidase (S. cerevisiae). (16)
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)
From a large Phadia repository of human blood serum – a subset of serum from 668 individuals with positive IgE antibody against 17 fungal species (but devoid of clinical history) – 337 were shown to be sensitised to S. cerevisiae. (32)
S. cerevisiae has also been reported to exacerbate atopic dermatitis. (33) 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. (34)
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 experienced generalized urticaria and asthma after eating pizza and bread, but only when fresh from the oven. Sensitisation 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 led to an immunotolerance with progressive reduction of symptoms. Why the allergens were active only in ready-baked foods could not be explained. (35)
Whether patients with hypersensitivity to S. cerevisiae should avoid ingesting this yeast in their diet is controversial. In a study in which samples of beer, aged red wine, young white wine, sparkling wine and extracts of fresh wheat bread and dried rye bread were analysed for evidence of 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. (33)
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 ketchup). 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. (36)
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. (19) 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 investigation with recombinant gp200 will elucidate the role of this glycoprotein, both in atopic dermatitis and in Crohn’s disease. (20)
A study described a 29-year-old mould-sensitised woman who developed multiple anaphylactic reactions after ingesting a yeast preparation (‘yeast extract’) widely used by the food industry as flavouring. Skin-prick and serum IgE test results were positive to several moulds and to the 2 pasta sauces implicated, the yeast ingredient, and a food-quality yeast extract. The patient was able to eat bakery products freely but experienced severe allergic reactions after eating sauces and other foods containing yeast as flavouring. Radioallergosorbent test inhibition studies confirmed that the sauces contained cross-reacting yeast and mould allergens. The commercial yeast extract responsible was suggested to be Saccharomyces pastorianus (lager yeast). (37) Anaphylaxis to yeast reported to the national Finnish register, in which physicians voluntarily report on patients with severe allergic reactions, totalled 530 cases of severe allergic reactions. (38) The specific yeast was not described.
b. 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 mouldy 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. (28) 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. (39)
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 Mucor. 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’. (40)
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. (41)
A study reported over 2 decades ago that 33% of a group of patients with migraine were hypersensitive to yeast. (42)
Compiled by Dr Harris Steinman
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