title: Effects of β-lactam antibiotics and fluoroquinolones on human gut microbiota in relation to Clostridium difficile associated diarrhea.
abstract: Clostridium difficile infections are an emerging health problem in the modern hospital environment. Severe alterations of the gut microbiome with loss of resistance to colonization against C. difficile are thought to be the major trigger, but there is no clear concept of how C. difficile infection evolves and which microbiological factors are involved. We sequenced 16S rRNA amplicons generated from DNA and RNA/cDNA of fecal samples from three groups of individuals by FLX technology: (i) healthy controls (no antibiotic therapy); (ii) individuals receiving antibiotic therapy (Ampicillin/Sulbactam, cephalosporins, and fluoroquinolones with subsequent development of C. difficile infection or (iii) individuals receiving antibiotic therapy without C. difficile infection. We compared the effects of the three different antibiotic classes on the intestinal microbiome and the effects of alterations of the gut microbiome on C. difficile infection at the DNA (total microbiota) and rRNA (potentially active) levels. A comparison of antibiotic classes showed significant differences at DNA level, but not at RNA level. Among individuals that developed or did not develop a C. difficile infection under antibiotics we found no significant differences. We identified single species that were up- or down regulated in individuals receiving antibiotics who developed the infection compared to non-infected individuals. We found no significant differences in the global composition of the transcriptionally active gut microbiome associated with C. difficile infections. We suggest that up- and down regulation of specific bacterial species may be involved in colonization resistance against C. difficile providing a potential therapeutic approach through specific manipulation of the intestinal microbiome.
authors.affiliation: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Knecht
authors.affiliation: Institute for General Microbiology (IFAM), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Sven C
authors.initials: SC
authors.lastname: Neulinger
authors.affiliation: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Femke Anouska
authors.initials: FA
authors.lastname: Heinsen
authors.affiliation: Institute of Medical Informatics and Statistics (IMIS), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Knecht
authors.affiliation: Institute for General Microbiology (IFAM), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schilhabel
authors.affiliation: Institute for General Microbiology (IFAM), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Schmitz
authors.affiliation: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Systems and Synthetic Biology, Wageningen University, Wageningen, The Netherlands ; LifeGlimmer GmbH, Berlin, Germany.
authors.forename: Vitor Martins
authors.initials: VM
authors.lastname: dos Santos
authors.affiliation: Laboratory of Enzyme Discovery, CSIC - Institute of Catalysis, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU), Kiel, Germany.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Rosenstiel
authors.affiliation: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU), Kiel, Germany ; Department of Internal Medicine I, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU), Kiel, Germany ; Department of Internal Medicine I, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
authors.forename: Anette K
authors.initials: AK
authors.lastname: Friedrichs
authors.affiliation: Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University (CAU), Kiel, Germany ; Department of Internal Medicine I, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Ott
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D016360:Clostridioides difficile / Q000187:drug effects* / Q000472:pathogenicity; D003015:Clostridium Infections / Q000188:drug therapy; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology; D024841:Fluoroquinolones / Q000494:pharmacology* / Q000627:therapeutic use; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D064307:Microbiota / Q000187:drug effects*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013407:Sulbactam / Q000494:pharmacology; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D002511:Cephalosporins; D024841:Fluoroquinolones; D012336:RNA, Ribosomal, 16S; D047090:beta-Lactams; D000667:Ampicillin; D013407:Sulbactam