Effect of biotherapeutics on cyclosporin-induced Clostridium difficile infection in mice

Abstract

Background and aim: Immunosuppressive therapy may precipitate Clostridium difficile associated disease (CDAD). We evaluated the role of cyclosporin in the development of CDAD in the experimental mouse model and studied the effect of probiotic and epidermal growth factor (EGF) as biotherapeutics measures.

Methods: BALB/c mice (n = 24) were divided into four groups. Group I animals not given any inoculum served as controls. Animals in the remaining three groups (Group II, III and IV) were given cyclosporin daily from days 1-7 followed by C. difficile inoculum on day 8. Additionally, the animals received Lactobacillus acidophilus (Group III) and EGF (Group IV) for one-week post C. difficile challenge. The animals were evaluated for colonization and toxin production by C. difficile, myeloperoxidase (MPO) activity and histopathological changes.

Results: Clostridium difficile was colonized and elaborated its toxins in animals receiving cyclosporin and C. difficile. MPO activity was significantly higher (P < 0.05) and histopathological epithelial damage, cryptitis and acute inflammatory changes were seen in the cecum and colon. C. difficile count, toxins A and B titers and MPO activity were significantly lowered (P < 0.05) in animals receiving probiotic and EGF. Histopathologically, mucodepletion and inflammatory infiltrate were decreased in the biotherapeutic receiving animals.

Conclusions: Cyclosporin led to the development of mild to moderate CDAD in animals. Administration of biotherapeutics reduced the severity of CDAD. Future clinical trials are needed for further investigation of these potential biotherapeutic measures.