Saccharomyces cerevisiae is a common dietary organism well known as baker's yeast or brewer's yeast. 1 It is not considered a pathogen, and few cases of infections in humans or animals have been reported. 2–11 It has been associated with a fungemia in a neutropenic patient 2 and with chronic diarrhea in a German shepherd dog. 12
In several cases of ulcerative colitis (UC), unresponsive to therapy diarrhea has been associated with opportunistic pathogens like cytomegalovirus and Candida albicans during corticosteroid or immunosuppressant treatment. 13,14 The current case demonstrates the potential role for S. cerevisiae of inducing infectious colitis and of mimicking an exacerbation of UC. Despite the rarity of this infection, the yeast stool culture should be considered in patients refractory to the treatment of ulcerative colitis. The occurrence of S. cerevisiae–related diarrhea has not been previously reported in a human being.
Antibodies to S. cerevisiae (ASCA) have been used in the diagnosis of inflammatory bowel diseases. 15–17 A small percentage of patients affected by UC (10–15%) seem to be ASCA-positive. We speculate that the presence of S. cerevisiae enteric colonization could alter the prevalence of such antibodies.
A 30-year-old man with a 10-year history of UC was admitted to our hospital because of a 7-day history of watery diarrhea and abdominal pain. A diagnosis of UC was made in May 1991 when he presented with persistent bloody diarrhea with mucus and abdominal discomfort. Multiple consecutive stool samples analyzed for enteric pathogenic bacteria, parasite, and toxin were negative. Colonoscopy showed left colitis. Biopsies showed severe chronic inflammation with crypt distortion and the presence of crypt abscesses, which is consistent with UC. He was treated with 2 months of tapering corticosteroid therapy. His symptoms improved to a mean of one to two formed stools a day, and he was started on maintenance therapy with sulfasalazine 2 g/d. The patient had two acute exacerbations in May 1996 and in December 2001, both occurring after he stopped therapy with sulfasalazine. During the second exacerbation, colonoscopy revealed a pancolitis. Corticosteroids were able in both situations to control the disease.
In February 2001 he was treated with sulfasalazine 4 g/d tapered to 2 g/d in 2 months. In August 2001, he presented with symptoms of 10 to 15 watery bowel movements daily, which were rarely bloody and were resistant to loperamide therapy; he had no fever or abdominal pain. He was admitted to our hospital without pain, and examination revealed abdominal tenderness. Laboratory data showed a normal white blood cell count of 7.7 thousand/μL (normal range, 4.0–9.8 thousand/μL), a hemoglobin level of 16.3 g/dL (normal range, 13.0–17.0), an erythrocyte sedimentation rate of 2 mm, and a C-reactive protein of less than 3 mg/L. On the second day of admission, he underwent colonoscopy, which showed diffuse erythema and loss of the normal vasculature in the left colon. Sigmoidal biopsies were obtained. From the third to the fifth day, stool culture, stool toxin, and stool parasite were performed. On day 5 of admission, the patient's biopsies were reviewed and showed mild chronic inflammation. Stool culture, stool Clostridium difficile toxin × 3, and stool parasite proved negative for ova or parasites but positive for yeast. On the sixth day, three yeast stool cultures were performed and S. cerevisiae was found in all samples. A serum sample was collected from the patient, and IgG and IgA ASCA were tested with a commercially available kit (Medimar, Milan; Italy; cut off values to define seropositive: 40 EU/mL for IgG and 20 EU/mL for IgA). IgG proved negative (13 EU/mL), whereas IgA (51 EU/mL) was positive. Fluconazole (400 mg/d) was then administered, and after 4 days, the stools became well-formed at a frequency of twice per day. His abdominal pain and tenderness improved, and he was discharged after 6 days. He continued fluconazole treatment for a week. The patient was seen 3 months after the end of fluconazole treatment and yeast stool cultures were negative. He was in good health and had one or two daily bowel movements of formed stools. He continued sulfasalazine 2 g/d therapy for maintenance. Serum testing for IgG and IgA ASCA were negative for IgG (28 EU/mL), but IgA remained positive (42 EU/mL).
S. cerevisiae is used worldwide in food preparations and is used in the treatment of C. difficile toxic diarrhea. 18 It has rarely been involved in human diseases and only in cases of immunosuppressed patients or in those who had prior courses of antibiotic treatment. 2–12 Diarrhea caused by S. cerevisiae was observed only in a dog. 3
Opportunistic colonic infections by viral and fungal agents are described in the literature as occurring in some cases of UC. In particular, C. albicans intestinal infections were shown to be the cause of some exacerbations of inflammatory bowel diseases. 14 Antibiotic treatment is considered one of the most common causes of intestinal fungal colonization through an overgrowth of yeast and a decrease of normal flora. It is possible that long-term sulfasalazine treatment could be related to an overgrowth of S. cerevisiae because of the antibiotic effect of its sulfapyridine component and to a secretory diarrhea. The pathogenesis of diarrhea may be related to the decrease of sulfasalazine intestinal metabolism and to a reduction of normal flora with relapsing of UC or to a toxic effect of yeast on the intestinal wall.
At the moment, the possibility that fluconazole could have a role in the treatment of UC exacerbation seems unlikely and the improvement of the patient after therapy seems related to antifungal treatment. Moreover, ASCAs have been related to Crohn's disease. 15–17 Because our patient, who had UC, was positive for IgA ASCA, we can speculate that yeast stool specimens should be investigated in inflammatory bowel disease (IBD) patients before performing ASCA determination to avoid a confounding factor. It is possible that S. cerevisiae infection (silent or not) could modify ASCA prevalence in IBD patients.
In conclusion, to our knowledge, this is the first report of diarrhea caused by S. cerevisiae in a human. This yeast infection should be investigated in the case of exacerbation of UC and treated with antifungal therapy. Moreover, further studies to investigate a possible role of S. cerevisiae infection on the prevalence of ASCA in IBD patients should be performed.
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