Downloaded from www.microbiologyresearch.org by IP: 54.70.40.11 On: Thu, 04 Apr 2019 16:57:56 J. Med. Microbiol. - Vol. 47 (1998), 11 1-1 16 0 1998 The Pathological Society of Great Britain and Ireland MYCOLOGY Dose effect of oral Saccharomyces boulardii treatments on morbidity and mortality in immunosuppressed mice L. A. PERET FILHO, F. J. PENNA, E. A. BAMBIRRA* and J. R. NlCOLl-/= Departamento de Pediatria and * Departamento de Anatomia Patologica, Faculdade de Medicina and t Departamento de Microbiologia, lnstituto de Cikncias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte MG, Brazil Survival, weight loss, translocation and histological alterations in the terminal ileum, liver and spleen were studied in mice simultaneously immunosuppressed with cyclophosphamide and treated or not with Saccharomyces boulardii until the death of all animals. The animals were divided into five groups: C1 (not immunosuppressed, not treated); C2 (immunosuppressed, not treated); B1 (immunosuppressed, treated with S. boulardii 10.0 mg); B2 (immunosuppressed, treated with S. boulardii 1.0 mg) and B3 (immunosuppressed, treated with S. boulardii 0.1 mg). Survival was higher in group B3 than in the other immunosuppressed groups. Weight loss was observed for all groups except C1. By day 7, some animals from each group were killed by ether inhalation for the determination of bacterial translocation and histopathological examination. Bacterial translocation to the liver was lower in groups C1 and B3 than in the other groups. The highest translocation to the liver and spleen was observed in group B1. Low S. boulardii translocation was observed in some animals, principally to the mesenteric lymph nodes. Histopathological examination showed a decrease in epithelial cell turnover with villus length reduction and loss of brush borders in group C2. Relative protection against these alterations was obtained when the animals were treated with the yeast, independently of the dose. Higher expression of the lymphoid component was also noted in the ileal lamina propria, liver and spleen of mice treated with the yeast, together with activation of the reticulo-endothelial system, when compared with group C2 where lymphocyte depletion was observed. This study suggests a relative protection of immunosuppressed animals by treatment with S. boulardii, but this phenomenon was inversely proportional to the yeast dose. Introduction Aggressive cytostatic treatment applied for remission induction therapy in leukaemic patients results in increasing granulocytopenic episodes, as well as serious damage to the epidermal and mucosal barriers and deterioration of humoral defence and cell im- munity. Therefore, severe bacterial and deep mycotic infections are the main cause of complications and death in patients with acute leukaemia [I]. The majority of these severe infections are of endogenous origin, i.e., caused by micro-organisms that have colonised the mucosal surface of the gastrointestinal (GI) tract and then have translocated. Translocation is defined as the passage of viable microbes from the GI tract across the mucosal barrier to extra-intestinal sites [2]. Bacterial translocation, as measured by the appearance of viable bacteria in extra-intestinal organs, is promoted by three major mechanisms: (i) physical disruption of the mucosal barrier [3], such as occurs with ischaemia and reperfusion injury during endotoxic or haemorrhagic shock; (ii) intestinal bacterial overgrowth following disruption of the GI ecology by oral antibiotics, protein malnutrition or shock; and (iii) decreased host immune defences [4], resulting from immuno- suppressive drugs or diseases such as cancer and AIDS. Received 4 Feb. 1997; revised version received 18 June 1997; accepted 1 July 1997. Corresponding author: Dr J. R. Nicoli. The growing number of immunological incompetence situations promoting translocation has justified re- search on immunotherapeutic agents which may