Encapsulation technologies for delivery of bioactive compounds to the gastrointestinal tract

Simple item page
dc.availability.bitstreamembargoed
dc.check.date2026-09-30
dc.contributor.advisorRoss, R. Paulen
dc.contributor.advisorHill, Colinen
dc.contributor.advisorexternalRea, Maryen
dc.contributor.authorO'Reilly, Catherine
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2021-09-23T15:43:53Z
dc.date.available2021-09-23T15:43:53Z
dc.date.issued2021-04-30
dc.date.submitted2021-04-30
dc.description.abstractUlcerative Colitis and other inflammatory bowel diseases (IBD) are increasingly linked to changes in the gut microbiome. In addition, gastrointestinal illnesses caused by infections by gut pathogens such as Clostridioides difficile (C. difficile) have been associated with antibiotic use. Indeed, Over-use of antibiotics is increasingly adding to the build-up of antibiotic resistance. This is leading to increased ineffectiveness of currently used antibiotics and consequently there is an urgent need to develop alternative treatments to traditionally administered antibiotics. The aim of this thesis was to investigate the effect of colon targeted bioactives (pharmabiotics) on the composition and function of the gut microbiota. Chapter 1 of the thesis is a literature review focused on the interaction of orally administered drugs for the treatment of IBD with the gut microbiota and with the host. The review highlights how understanding and manipulating these interactions may enhance treatment outcomes in the future and bring about new opportunities for precision medicine where microbiome/drug-host interactions are taken into account. Cyclosporine, a calcineurin inhibitor, has a protective role in the treatment of Ulcerative Colitis by down-regulating pro-inflammatory cytokine production. It is currently used for the treatment of refractory ulcerative colitis. Cyclosporine has traditionally been administered intravenously, however; prolonged systemic exposure can cause toxicity. Chapter 2 details a study in which we assessed the effect of a newly developed cyclosporine containing formulation on the composition and functionality of the gut microbiota. This novel delivery system was developed by Sigmoid Pharma (now Sublimity Therapeutics Ltd) to encapsulate cyclosporine for targeted delivery to the colon. In this way the concentration of cyclosporine delivered could be reduced. The results demonstrate that while the composition of the microbiota remains unaffected, the functionality of the microbiota may be changed given that levels of short chain fatty acids were affected significantly. Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria including the gut pathogen C. difficile. In Chapter 3 we assessed the activity of nisin at a range of concentrations from 0-500 µM against C. difficile in an ex vivo model colon fermentor and determined the minimum inhibitory concentration at which C. difficile growth is suppressed (50M) while having minimal impact on the faecal microbiota. This study opens up the potential of nisin as a therapeutic for clostridial gut infections. Chapter 4 outlines the impact of fidaxomicin, nisin, thuricin CD (at equimolar concentrations) and a no treatment control on the gut microbiota in the model colon system, Fidaxomicin is used primarily in patients not responding to the traditional antibiotics routinely used to treat Clostridioides difficile Infection (CDI). Nisin and thuricin CD are bacteriocins with broad or narrow spectrum of activity, respectively. Fidaxomicin and nisin were found to have a broader spectrum of activity that was not selective just for C. difficile and related species, while thuricin CD exhibited a largely selective spectrum of activity limited primarily to C. difficile. Nisin is the only commercially available highly purified bacteriocin which is approved safe for use in food and for human consumption. Because of its peptide nature it is sensitive to proteolytic digestion. In Chapter 5 the ability of nisin in both an encapsulated and unencapsulated form to reach the lower porcine GIT, was investigated. This study disproved the dogma that nisin is broken down in the mammalian gut by demonstrating that intact nisin survives intestinal transit where it can modify the gut microbiota. In particular, Gram-positive bacteria of the Firmicutes Phylum were proportionally reduced which also was associated with reductions in some short chain fatty acid – particularly butyrate. Importantly, these changes to the gut microbiota were reversed quickly following cessation of feeding the bacteriocin. Overall, this work evaluates the usefulness of encapsulating bioactives for targeted release to treat GIT illnesses. These studies also demonstrate the potential of bacteriocins as an alternative to antibiotics in the treatment of GI pathogens such as C. difficile and as antimicrobial tools to modify the composition of the microbiota in vivo despite their proteinaceous nature.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Reilly, C. 2021. Encapsulation technologies for delivery of bioactive compounds to the gastrointestinal tract. PhD Thesis, University College Cork.en
dc.identifier.endpage237en
dc.identifier.urihttps://hdl.handle.net/10468/11996
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© 2021, Catherine O'Reilly.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectClostridioides difficileen
dc.subjectCyclosporineen
dc.subjectNisinen
dc.subjectInflammatory bowel diseasesen
dc.subjectGut microbiotaen
dc.titleEncapsulation technologies for delivery of bioactive compounds to the gastrointestinal tracten
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
Files
Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
Final Thesis Doctor of Philosophy COR August 21.pdf
Size:
5.07 MB
Format:
Adobe Portable Document Format
Description:
Full Text E-thesis
Thumbnail Image
Name:
3. SubmissionforExaminationForm CORpdf - Catherine O'Reilly.pdf
Size:
542.66 KB
Format:
Adobe Portable Document Format
Description:
Submission for Examination Form
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
5.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Research Theses Submission
APC Microbiome Ireland - Doctoral Theses
College of Science, Engineering and Food Science - Doctoral Theses
Microbiology - Doctoral Theses