Your browser doesn't support javascript.
loading
Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota.
Sougiannis, A T; VanderVeen, B N; Enos, R T; Velazquez, K T; Bader, J E; Carson, M; Chatzistamou, I; Walla, M; Pena, M M; Kubinak, J L; Nagarkatti, M; Carson, J A; Murphy, E A.
Afiliação
  • Sougiannis AT; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • VanderVeen BN; Department of Exercise Science, School of Public Health, University of South Carolina, SC 29201, USA.
  • Enos RT; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • Velazquez KT; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • Bader JE; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • Carson M; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • Chatzistamou I; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • Walla M; Department of Chemistry, University of South Carolina, SC 29201, USA.
  • Pena MM; Department of Biology, University of South Carolina, SC 29201, USA.
  • Kubinak JL; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • Nagarkatti M; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
  • Carson JA; College of Health Professions, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
  • Murphy EA; Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA. Electronic address: angela.murphy@uscmed.sc.edu.
Brain Behav Immun ; 80: 44-55, 2019 08.
Article em En | MEDLINE | ID: mdl-30807838
Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10-15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fluoruracila / Microbioma Gastrointestinal Limite: Animals Idioma: En Revista: Brain Behav Immun Assunto da revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fluoruracila / Microbioma Gastrointestinal Limite: Animals Idioma: En Revista: Brain Behav Immun Assunto da revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Holanda