The gut microbiome diversity of Clostridioides difficile-inoculated mice treated with vancomycin and fidaxomicin
- PMID: 32165071
- DOI: 10.1016/j.jiac.2019.12.020
The gut microbiome diversity of Clostridioides difficile-inoculated mice treated with vancomycin and fidaxomicin
Abstract
Objective: To investigate the effect of vancomycin and fidaxomicin on the diversity of intestinal microbiota in a mouse model of Clostridioides difficile infection.
Methods: Mice were divided into 11 models (4 mice per model): 6 uninoculated models and 5 models inoculated with C. difficile BI/NAP1/027. Inoculated models were prepared using intraperitoneal clindamycin followed by inoculation with C. difficile BI/NAP1/027. Uninoculated and C. difficile-inoculated mice received 2 or 7 days' vancomycin or fidaxomicin. Clostridium butyricum MIYAIRI 588 probiotic and lactoferrin prebiotic were administered for 10 days to uninoculated mice. Intestinal microbiome composition was investigated by sequence analyses of bacterial 16S rRNA genes from faeces, and microbiota diversity estimated.
Results: In uninoculated, untreated ('normal') mice, Clostridia (57.8%) and Bacteroidia (32.4%) accounted for the largest proportions of gut microbiota. The proportion of Clostridia was numerically reduced in C. difficile-inoculated versus normal mice. Administration of vancomycin to C. difficile-inoculated mice reduced the proportions of Bacteroidia and Clostridia, and increased that of Proteobacteria. Administration of fidaxomicin to C. difficile-inoculated mice reduced the proportion of Clostridia to a lesser extent, but increased that of Bacteroidia. Microbiota diversity was lower in C. difficile-inoculated versus normal mice (164.5 versus 349.1 operational taxonomic units (OTUs), respectively); treatment of C. difficile-inoculated mice with 7 days' vancomycin reduced diversity to a greater extent than did 7 days' fidaxomicin treatment (26.2 versus 134.2 OTUs, respectively).
Conclusions: Both C. difficile inoculation and treatment with vancomycin or fidaxomicin reduced microbiota diversity; however, dysbiosis associated with fidaxomicin was milder than with vancomycin.
Keywords: 16S rRNA; Clostridioides difficile; Fidaxomicin; Microbiota.
Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest TY has received a Grant-in-Aid for Young Scientists B from JSPS KAKENHI (grant number 15K19593). KT has received a Grant-in-Aid for Private University Research Branding Project from MEXT. KC is an employee of Astellas Pharma, Inc. HK, KA and YI have no conflicts to disclose.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
