title: Metabolism links bacterial biofilms and colon carcinogenesis.
abstract: Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression.
authors.affiliation: Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Johnson
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Dejea
authors.affiliation: Center of Surgical Gastroenterology, Karolinska University Hospital, 171 77 Stockholm, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Edler
authors.affiliation: Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Linh T
authors.initials: LT
authors.lastname: Hoang
authors.affiliation: Departments of Chemical Physiology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Santidrian
authors.affiliation: Departments of Chemical Physiology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Brunhilde H
authors.initials: BH
authors.lastname: Felding
authors.affiliation: Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Julijana
authors.initials: J
authors.lastname: Ivanisevic
authors.affiliation: Departments of Chemistry, Genetics, and Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cho
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wick
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hechenbleikner
authors.affiliation: Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Winnie
authors.initials: W
authors.lastname: Uritboonthai
authors.affiliation: Department of Surgery, Scripps Clinic Medical Group, La Jolla, CA 92037, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Goetz
authors.affiliation: Departments of Oncology and Medicine and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Casero
authors.affiliation: Departments of Oncology and Medicine and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.affiliation: Resphera Biosciences, Baltimore, MD 21231, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: White
authors.affiliation: Departments of Chemistry, Genetics, and Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Patti
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA; Departments of Oncology and Medicine and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA. Electronic address: csears@jhmi.edu.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Sears
authors.affiliation: Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: siuzdak@scripps.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
mesh_terms: D001419:Bacteria / Q000378:metabolism*; D018407:Bacterial Physiological Phenomena; D018441:Biofilms; D003110:Colonic Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D013096:Spermine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D013096:Spermine; C029453:N',N''-diacetylspermine