title: Evaluation of mucositis induced by irinotecan after microbial colonization in germ-free mice.
abstract: Mucositis is one of the most debilitating side effects of chemotherapy and some previous studies suggest a role for indigenous microbiota in the course of this pathology. Therefore, the aim of our study was to evaluate the differences in phenotype between germ-free (GF) and conventional (CV) mice, and the role of β-glucuronidase-producing bacteria in the development of irinotecan treatment in a murine model. After mucositis induction, CV mice showed a significant increase in all inflammatory parameters when compared to GF mice. CV animals also showed more lesions of the intestinal epithelium, coherent with their higher intestinal permeability. The conventionalization of GF animals reversed their phenotype to that found in CV mice. In addition, gnotobiotic mice monoassociated with an Escherichia coli strain producing β-glucuronidase showed an increased permeability when compared to gnotobiotic mice monoassociated with an E. coli strain deleted for the gene encoding β-glucuronidase, but these did not show any differences in the influx of neutrophils, eosinophils or histological characteristics. Our data confirmed that components of the gut microbiota are involved in the signs of mucositis. Nevertheless, other mechanisms than this enzyme are involved in the irinotecan treatment, since the monoassociation was not able to restore the entire phenotype observed in the CV animals with irinotecan treatment in our murine model.
authors.affiliation: Department of Microbiology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvia H S P
authors.initials: SHSP
authors.lastname: Pedroso
authors.affiliation: Department of Microbiology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Department of Biochemistry and Immunology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Angélica T
authors.initials: AT
authors.lastname: Vieira
authors.affiliation: Department of Microbiology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rafael W
authors.initials: RW
authors.lastname: Bastos
authors.affiliation: Department of Biochemistry and Immunology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Jamil S
authors.initials: JS
authors.lastname: Oliveira
authors.affiliation: Department of General Pathology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Christiane T
authors.initials: CT
authors.lastname: Cartelle
authors.affiliation: Department of General Pathology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rosa M E
authors.initials: RME
authors.lastname: Arantes
authors.affiliation: Department of Morphology, Medical School, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Pedro M G
authors.initials: PMG
authors.lastname: Soares
authors.affiliation: Department of Basic Nursing, School of Nursing, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Simone V
authors.initials: SV
authors.lastname: Generoso
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Valbert N
authors.initials: VN
authors.lastname: Cardoso
authors.affiliation: Department of Biochemistry and Immunology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Department of Microbiology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Jacques R
authors.initials: JR
authors.lastname: Nicoli
authors.affiliation: Department of Microbiology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Flaviano S
authors.initials: FS
authors.lastname: Martins
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001419:Bacteria / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D007413:Intestinal Mucosa / Q000473:pathology; D000077146:Irinotecan; D051379:Mice; D052016:Mucositis / Q000139:chemically induced*
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D002166:Camptothecin