Dataset Information

Vancomycin Treatment Alters Humoral Immunity and Intestinal Microbiota in an Aged Mouse Model of Clostridium difficile Infection.

ABSTRACT:

Background

The elderly host is highly susceptible to severe disease and treatment failure in Clostridium difficile infection (CDI). We investigated how treatment with vancomycin in the aged host influences systemic and intestinal humoral responses and select intestinal microbiota.

Methods

Young (age, 2 months) and aged (age, 18 months) C57BL/6 mice were infected with VPI 10463 after exposure to broad-spectrum antibiotics. Vancomycin was given 24 hours after infection, and treatment was continued for 5 days. At select time points, specimens of serum and intestinal tissue and contents were collected for histopathologic analysis, to measure antibody levels and the pathogen burden, and to determine the presence and levels of select intestinal microbiota and C. difficile toxin.

Results

Levels of disease severity, relapse, and mortality were increased, and recovery from infection was slower in aged mice compared to young mice. Serum levels of immunoglobulin M, immunoglobulin A, and immunoglobulin G against C. difficile toxin A were depressed in aged mice, and vancomycin treatment reduced antibody responses in both age groups. While baseline levels of total bacterial load, Bacteroidetes, Firmicutes, and Enterobacteriaceae were mostly similar, aged mice had a significant change in the Firmicutes to Bacteroidetes ratio with vancomycin treatment.

Conclusions

Vancomycin treatment decreases the systemic humoral response to CDI. Increased mortality from and recurrence of CDI in the aged host are associated with an impaired humoral response and a greater susceptibility to vancomycin-induced alteration of intestinal microbiota.

SUBMITTER: van Opstal E

PROVIDER: S-EPMC4907406 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vancomycin Treatment Alters Humoral Immunity and Intestinal Microbiota in an Aged Mouse Model of Clostridium difficile Infection.

van Opstal Edward E Kolling Glynis L GL Moore John H JH Coquery Christine M CM Wade Nekeithia S NS Loo William M WM Bolick David T DT Shin Jae Hyun JH Erickson Loren D LD Warren Cirle A CA

The Journal of infectious diseases 20160224 1

<h4>Background</h4>The elderly host is highly susceptible to severe disease and treatment failure in Clostridium difficile infection (CDI). We investigated how treatment with vancomycin in the aged host influences systemic and intestinal humoral responses and select intestinal microbiota.<h4>Methods</h4>Young (age, 2 months) and aged (age, 18 months) C57BL/6 mice were infected with VPI 10463 after exposure to broad-spectrum antibiotics. Vancomycin was given 24 hours after infection, and treatmen ...[more]

PMID: 26917573

Similar Datasets

Project description:Ridinilazole, a novel targeted antibacterial being developed for the treatment of C. difficile infection (CDI) and prevention of recurrence, was shown in a recent Phase 2 study to be superior to vancomycin with regard to the primary efficacy measure, sustained clinical response (SCR), with the superiority being driven primarily by marked reductions in the rates of CDI recurrence within 30 days. Tolerability of ridinilazole was comparable to that of vancomycin. The current nested cohort study compared the effects of ridinilazole and vancomycin on fecal microbiota during and after treatment among participants in the Phase 2 study. Changes in the microbiota were assessed using qPCR and high-throughput sequencing on participants' stools collected at multiple time-points (baseline [Day 1], Day 5, end-of-treatment [EOT; Day 10], Day 25, end-of-study [EOS; Day 40], and at CDI recurrence). qPCR analyses showed profound losses of Bacteroides, C. coccoides, C. leptum, and Prevotella groups at EOT with vancomycin treatment, while ridinilazole-treated participants had a modest decrease in C. leptum group levels at EOT, with levels recovering by Day 25. Vancomycin-treated participants had a significant increase in the Enterobacteriaceae group, with this increase persisting beyond EOT. At EOT, alpha diversity decreased with both antibiotics, though to a significantly lesser extent with ridinilazole (p <0.0001). Beta diversity analysis showed a significantly larger weighted Unifrac distance from baseline-to-EOT with vancomycin. Taxonomically, ridinilazole had a markedly narrower impact, with modest reductions in relative abundance in Firmicutes taxa. Microbiota composition returned to baseline sooner with ridinilazole than with vancomycin. Vancomycin treatment resulted in microbiome-wide changes, with significant reductions in relative abundances of Firmicutes, Bacteroidetes, Actinobacteria, and a profound increase in abundance of Proteobacteria. These findings demonstrate that ridinilazole is significantly less disruptive to microbiota than vancomycin, which may contribute to the reduced CDI recurrence observed in the Phase 2 study.

Dataset Information

Vancomycin Treatment Alters Humoral Immunity and Intestinal Microbiota in an Aged Mouse Model of Clostridium difficile Infection.

Background

Methods

Results

Conclusions

Publications

Vancomycin Treatment Alters Humoral Immunity and Intestinal Microbiota in an Aged Mouse Model of Clostridium difficile Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets