Effects of cyclophosphamide on immune system and gut microbiota in mice

Microbiol Res. 2015 Feb:171:97-106. doi: 10.1016/j.micres.2014.11.002. Epub 2014 Dec 2.

Abstract

Cyclophosphamide (CP) is the most commonly used drug in autoimmune disease, cancer, blood and marrow transplantation. Recent data revealed that therapy efficacy of CP is gut microbiota-dependent. So, it is very important to understand how CP affects intestinal microbiota and immune function. In this study, the effects of CP on mice immuno-activity were firstly evaluated, then, the fecal microbiota from normal and CP-treated mice was compared, and the characteristic bacterial diversity and compositions were identified, using 454 pyrosequencing technology. The results showed that CP reduced the diversity and shifted the fecal microbiota composition. Specifically, CP treatment decreased the proportion of Bacteroidetes while increased the proportion of Firmictutes in the microbial community. Most importantly, specific microbiota signatures belonging to Bacteroides acidifaciens, Streptococcaceae and Alistipes were also identified, which would provide new insight into the efficacy and side effects in clinical usage of CP. This should be helpful for further demonstration of CP's action mechanism, development of personalized therapy strategies, and prediction of potential side effects related to various treatment regimens of CP.

Keywords: Cyclophosphamide; Gut microbiota; High-throughput sequencing; Immuno-activity.

MeSH terms

  • Animals
  • Biodiversity
  • Cluster Analysis
  • Cyclophosphamide / pharmacology*
  • Cytokines / blood
  • Immune System / drug effects*
  • Immunity / drug effects
  • Immunosuppressive Agents / pharmacology*
  • Intestines / drug effects*
  • Intestines / microbiology*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Male
  • Mice
  • Microbiota*
  • Phylogeny
  • RNA, Ribosomal, 16S / genetics

Substances

  • Cytokines
  • Immunosuppressive Agents
  • RNA, Ribosomal, 16S
  • Cyclophosphamide