title: Chemopreventive Metabolites Are Correlated with a Change in Intestinal Microbiota Measured in A-T Mice and Decreased Carcinogenesis.
abstract: Intestinal microbiota play a significant role in nutrient metabolism, modulation of the immune system, obesity, and possibly in carcinogenesis, although the underlying mechanisms resulting in disease or impacts on longevity caused by different intestinal microbiota are mostly unknown. Herein we use isogenic Atm-deficient and wild type mice as models to interrogate changes in the metabolic profiles of urine and feces of these mice, which are differing in their intestinal microbiota. Using high resolution mass spectrometry approach we show that the composition of intestinal microbiota modulates specific metabolic perturbations resulting in a possible alleviation of a glycolytic phenotype. Metabolites including 3-methylbutyrolactone, kyneurenic acid and 3-methyladenine known to be onco-protective are elevated in Atm-deficient and wild type mice with restricted intestinal microbiota. Thus our approach has broad applicability to study the direct influence of gut microbiome on host metabolism and resultant phenotype. These results for the first time suggest a possible correlation of metabolic alterations and carcinogenesis, modulated by intestinal microbiota in A-T mice.
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, D.C., United States of America.|Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Amrita K
authors.initials: AK
authors.lastname: Cheema
authors.affiliation: Department of Environmental Health Sciences, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Irene
authors.initials: I
authors.lastname: Maier
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Tyrone
authors.initials: T
authors.lastname: Dowdy
authors.affiliation: Department of Biostatistics, Biomathematics and Bioinformatics, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Rajbir
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Plant Pathology and Microbiology, University of California Riverside, Riverside, California, United States of America.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ruegger
authors.affiliation: Department of Plant Pathology and Microbiology, University of California Riverside, Riverside, California, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Borneman
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, D.C., United States of America.|Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
authors.affiliation: Department of Environmental Health Sciences, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Pathology Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Radiation Oncology, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Schiestl
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic; D000069196:Gastrointestinal Microbiome; D007414:Intestinal Neoplasms; D051379:Mice; D018345:Mice, Knockout
chemical_list: C030033:3-methylbutyrolactone; C025946:3-methyladenine; D000225:Adenine; D015107:4-Butyrolactone