Impact of a phage cocktail targeting Escherichia coli and Enterococcus faecalis as members of a gut bacterial consortium in vitro and in vivo

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dc.contributor.authorButtimer, Colinen
dc.contributor.authorSutton, Thomas D. S.en
dc.contributor.authorColom, Joanen
dc.contributor.authorMurray, Ellenen
dc.contributor.authorBettio, Pedro H.en
dc.contributor.authorSmith, Lindaen
dc.contributor.authorBolocan, Andrei Sorinen
dc.contributor.authorShkoporov, Andrey N.en
dc.contributor.authorOka, Akihikoen
dc.contributor.authorLiu, Boen
dc.contributor.authorHerzog, Jeremy W.en
dc.contributor.authorSartor, R. Balfouren
dc.contributor.authorDraper, Lorraine A.en
dc.contributor.authorRoss, R. Paulen
dc.contributor.authorHill, Colinen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderJanssen Biotechen
dc.date.accessioned2024-04-18T10:47:33Z
dc.date.available2024-04-18T10:47:33Z
dc.date.issued2022en
dc.description.abstractEscherichia coli and Enterococcus faecalis have been implicated as important players in human gut health that have been associated with the onset of inflammatory bowel disease (IBD). Bacteriophage (phage) therapy has been used for decades to target pathogens as an alternative to antibiotics, but the ability of phage to shape complex bacterial consortia in the lower gastrointestinal tract is not clearly understood. We administered a cocktail of six phages (either viable or heat-inactivated) targeting pro-inflammatory Escherichia coli LF82 and Enterococcus faecalis OG1RF as members of a defined community in both a continuous fermenter and a murine colitis model. The two target strains were members of a six species simplified human microbiome consortium (SIHUMI-6). In a 72-h continuous fermentation, the phage cocktail caused a 1.1 and 1.5 log (log10 genome copies/mL) reduction in E. faecalis and E. coli numbers, respectively. This interaction was accompanied by changes in the numbers of other SIHUMI-6 members, with an increase of Lactiplantibacillus plantarum (1.7 log) and Faecalibacterium prausnitzii (1.8 log). However, in germ-free mice colonized by the same bacterial consortium, the same phage cocktail administered twice a week over nine weeks did not cause a significant reduction of the target strains. Mice treated with active or inactive phage had similar levels of pro-inflammatory cytokines (IFN-y/IL12p40) in unstimulated colorectal colonic strip cultures. However, histology scores of the murine lower GIT (cecum and distal colon) were lower in the viable phage-treated mice, suggesting that the phage cocktail did influence the functionality of the SIHUMI-6 consortium. For this study, we conclude that the observed potential of phages to reduce host populations in in vitro models did not translate to a similar outcome in an in vivo setting, with this effect likely brought about by the reduction of phage numbers during transit of the mouse GIT.en
dc.description.sponsorshipScience Foundation Ireland (Grant SFI/14/SPAPC/B3032)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid936083en
dc.identifier.citationButtimer, C., Sutton, T., Colom, J., Murray, E., Bettio, P.H., Smith, L., Bolocan, A.S., Shkoporov, A., Oka, A., Liu, B., Herzog, J.W., Sartor, R.B., Draper, L.A., Ross, R.P. and Hill, C. (2022) ‘Impact of a phage cocktail targeting Escherichia coli and Enterococcus faecalis as members of a gut bacterial consortium in vitro and in vivo’, Frontiers in Microbiology, 13, 936083 (19pp). doi: 10.3389/fmicb.2022.936083en
dc.identifier.doi10.3389/fmicb.2022.936083en
dc.identifier.endpage19en
dc.identifier.journaltitleFrontiers in Microbiologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/15811
dc.identifier.volume13en
dc.language.isoenen
dc.publisherFrontiers Media S.A.en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI ERC Development Programme/15/ERCD/3189/IE/GUTPHAGE: bacteriophage as agents to manipulate the microbiota for human health/en
dc.rights© 2022 Buttimer, Sutton, Colom, Murray, Bettio, Smith, Bolocan, Shkoporov, Oka, Liu, Herzog, Sartor, Draper, Ross and Hill. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectBacteriophageen
dc.subjectPhage cocktail therapyen
dc.subjectBacteria consortiumen
dc.subjectEscherichia colien
dc.subjectEnterococcus faecalisen
dc.subjectGuten
dc.subjectMurine modelen
dc.subjectFermentationen
dc.titleImpact of a phage cocktail targeting Escherichia coli and Enterococcus faecalis as members of a gut bacterial consortium in vitro and in vivoen
dc.typeArticle (peer-reviewed)en
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