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Saccharomyces

Is It a Probiotic or a Pathogen and What Is the Significance of an Elevated Anti–S. cerevisiae Antibody?

Floch, Martin H., M.D.

Journal of Clinical Gastroenterology: January 2003 - Volume 36 - Issue 1 - p 5-6
Editorials
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Clinical Professor of Medicine

Yale University School of Medicine

Norwalk and New Haven, Connecticut

Saccharomyces cerevisiae is found ubiquitously in baker's yeast, and S. boulardi is used as a probiotic. As such, we are commonly exposed to these yeasts in our society. There have only been sporadic reports of their involvement in significant human infections. In this issue of the Journal, there are two reports that demonstrate their potential harm. Riquelme et al. 1 working in Chile identified two cases of fungemia in immunosuppressed patients, and Candelli et al. 2 working in Italy identified two patients with ulcerative colitis in which they thought Saccharomyces caused an exacerbation of diarrhea.

S. cerevisiae is the most common species of the genus Saccharomyces. It is used in baker's yeast and, as a consequence, readily finds its way into our foods. 3S. boulardi is widely used as a probiotic to treat patients with recurrent Clostridia difficile–associated diarrhea. 4 Its use has also been suggested as a treatment for traveler's diarrhea. 1,2 In this issue of the Journal, Riquelme and colleagues 1 report two patients who were immunocompromised and were treated with S. boulardi for C. difficile–recurrent diarrhea. 1 Both patients developed a documented fungemia. The organism was identified as S. cerevisiae. The obvious questions raised by our reviewers and explained by the authors is how S. boulardi is related to S. cerevisiae. The authors worked with an established, accredited microbiology laboratory and microbiologist. They answered the question by stating that “S. boulardi strains are asporogenous strains of the species S. cerevisiae and therefore are not representatives of a distinct and separate species.”1 They felt that this was supported by recent microsatellite typing and explain the isolation of S. cerevisiae after culturing it from capsules of probiotic S. boulardi. To those of us who are practicing gastroenterologists, this is detailed mycology, but it is also apparent that mycologists disagree on this taxonomy. However, we must accept the clear possibility that the use of the probiotic in immunocompromised patients may result in fungemia from these reported cases. Certainly, the fact that these patients were immunocompromised raises the question of whether this select group is more susceptible than the average patient who develops C. difficile antibiotic–associated diarrhea. As Riquelme and colleagues point out, this is not the first report. There are now nine reported incidences of suspicion of S. boulardi causing fungemia. This would make the tenth report. There should be great caution in using this probiotic in immunocompromised patients.

In the other related report in this issue of the Journal, Candelli and colleagues 2 document the first case of S. cerevisiae–associated diarrhea in an immunocompetent patient with ulcerative colitis. As noted previously, S. cerevisiae is ubiquitous and is used in baker's yeast. Clinicians and laboratories rarely attempt to culture S. cerevisiae in patients with diarrhea. Although these authors feel that they have clearly documented the organism as related to the diarrhea, we find no other reports of such an observation. In reality, few clinicians or laboratories ever seek this organism in the stool. However, the treatment of this patient with antifungal therapy and the patient's rapid recovery speaks strongly for the fact that S. cerevisiae was the cause of the diarrhea in their patient.

Although this case is reported for the fact that the fungus may cause the diarrhea, it is of interest that this patient became IgA anti–S. cerevisiae antibody (ASCA)-positive and has remained positive. We do not know whether this patient was positive before the stools were reported positive for the organism. Furthermore, there is always the possibility that this patient has Crohn's colitis, although the case clearly seems to have evolved as simple ulcerative colitis. The sensitivity and specificity of ASCA remains a problem to most clinicians. ASCA is an antibody test for a variety of antigens from S. cerevisiae.5,6 It is also interesting to note that ASCA occurs frequently in unaffected relatives of patients with both Crohn's disease and ulcerative colitis. 9 However, there are questions as to the different strains of S. cerevisiae used in testing for the antibody, as well as the techniques used in measuring the antibody. 7–10 We should not forget that in early reports on ASCA there were significant levels in healthy controls and in patients with intestinal disease, such as celiac disease. 5,6

The question as to what is the significance of merely finding increased ASCA in a patient still exists. The reports of specificity must still be questioned, as the quotes of 90% specificity is in inflammatory bowel disease patients, and most studies did not include other controls with small or large bowel disease. An elevated ASCA now raises several possibilities. It can mean that the patient has had a small bowel break in the intestinal barrier or a very significant fungemia to cause an antibody response, or it could mean that there is significant intestinal disease or may be specific for Crohn's disease.

Interpretation of an elevated ASCA is a problem to clinicians, but it should not erase the importance of this finding. In a recent report by Joossens et al., 11 ASCA was helpful in discriminating among ulcerative colitis, Crohn's, and indeterminate colitis. But clinicians should keep in mind it is still early in our understanding of Saccharomyces organism's parasitic, probiotic, or pathogenic role. In a patient with chronic symptoms, ASCA certainly has a high specificity for intestinal disease, but requires careful interpretation in each individual case.

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REFERENCES

1. Riquelme AJ, Calvo MA, Guzmán AM, et al. Saccharomyces cerevisiae fungemia after Saccharomyces boulardii treatment in immunocompromised patients. J Clin Gastroenterol 2002; 36:41–3.
2. Candelli M, Nista EC, Armuzzi A, et al. Saccharomyces cerevisiae–associated diarrhea in an immunocompetent patient with ulcerative colitis. J Clin Gastroenterol 2002; 36:39–40.
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9. Annese V, Andreoli A, Andriulli A, et al. Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study. Am J Gastroenterol 2001; 96:2407–12.
10. Peeters M, Joossens S, Vermiere S, et al. Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophilic cytoplasmic autoantibodies in inflammatory bowel disease. Am J Gastroenterol 2001; 96:730–4.
11. Joossens S, Reinisch W, Vermeire S, et al. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology 2002; 122:1242–7.
© 2003 Lippincott Williams & Wilkins, Inc.