title: Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon.
abstract: Vancomycin, metronidazole, and the bacteriocin lacticin 3147 are active against a wide range of bacterial species, including Clostridium difficile. We demonstrate that, in a human distal colon model, the addition of each of the three antimicrobials resulted in a significant decrease in numbers of C. difficile. However, their therapeutic use in the gastrointestinal tract may be compromised by their broad spectrum of activity, which would be expected to significantly impact on other members of the human gut microbiota. We used high-throughput pyrosequencing to compare the effect of each antimicrobial on the composition of the microbiota. All three treatments resulted in a decrease in the proportion of sequences assigned to the phyla Firmicutes and Bacteroidetes, with a corresponding increase in those assigned to members of the Proteobacteria. One possible means of avoiding such "collateral damage" would involve the application of a narrow-spectrum antimicrobial with specific anti-C. difficile activity. We tested this hypothesis using thuricin CD, a narrow-spectrum bacteriocin produced by Bacillus thuringiensis, which is active against C. difficile. The results demonstrated that this bacteriocin was equally effective at killing C. difficile in the distal colon model but had no significant impact on the composition of the microbiota. This offers the possibility of developing a targeted approach to eliminating C. difficile in the colon, without collateral damage.
authors.affiliation: Teagasc, Moorepark Food Research Centre, Fermoy, County Cork, Ireland.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Rea
authors.forename: Alleson
authors.initials: A
authors.lastname: Dobson
authors.forename: Orla
authors.initials: O
authors.lastname: O'Sullivan
authors.forename: Fiona
authors.initials: F
authors.lastname: Crispie
authors.forename: Fiona
authors.initials: F
authors.lastname: Fouhy
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cotter
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
authors.forename: Barry
authors.initials: B
authors.lastname: Kiely
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
authors.forename: R Paul
authors.initials: RP
authors.lastname: Ross
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins / Q000494:pharmacology*; D001483:Base Sequence; D016360:Clostridioides difficile / Q000187:drug effects*; D003106:Colon / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D006801:Humans; D054892:Metagenome / Q000187:drug effects* / Q000235:genetics; D008795:Metronidazole / Q000494:pharmacology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C082508:lacticin 481; D008795:Metronidazole; C059740:thuricin; D014640:Vancomycin