A Detrimental Role of Immunosuppressive Drug, Dexamethasone, During Clostridium difficile Infection in Association with a Gastrointestinal Microbial Shift

Abstract

We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota.

Keywords: Antibiotics; Clostridium difficile infection; Gut; Immunosuppressive drug; Microbiota.

Fig. 1. Clinical presentation of mice in each group

Data on survival (A), diarrhea (B), and weight loss (C) of each group of mice are shown. Mice in group 1 (G1) were not treated with anything. Mice in groups 2 and 3 (G2 and G3) were treated with antibiotics or antibiotics with dexamethasone mixture for 5 days, respectively. Then the mice were challenged with 1 × 10⁶ spores of C. difficile UK6. The weight of mice and progression of the disease were monitored after the C. difficile challenge. G1: No antibiotics. G2: Clindamycin+antibiotics. G3: Clindamycin+antibiotics+dexamethasone.

Fig. 2. Taxonomic classification of the sequences at the genus level

Phylogenetic assessments were performed using the RDP classifier implemented in QIIME with a bootstrap cutoff of 80%. Phylum, class, order, family, and genus are presented in each legend. “Other” represents the unclassified taxon at each level of classification. The antibiotics treatments were continued for 5 days between 44 and 48 days of age. G1: No antibiotics. G2: Clindamycin+antibiotics. G3: Clindamycin + antibiotics + dexamethasone.