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As a result, recombinant bacteria are often outcompeted by the native gut flora, requiring high concentrations to alleviate disease pathology. These limitations support the need for novel mechanisms of treatment that improve oral delivery compliance and ease of use. Through the research described in this dissertation, we outline the potential to use bacteriophage as an alternative chassis for biologic production and delivery to the gastrointestinal tract, targeting and reducing symptoms of obesity and ulcerative colitis. Elucidation of this system presents a universal platform for the long-term amelioration of gastrointestinal disease through the use of lytic phage particles.","abstract_html":"Current treatments of gastrointestinal (gut) disease are limited by high dosing frequency, patient noncompliance, and complications circumventing the harsh conditions of the upper gastrointestinal tract (e.g. stomach), leading to therapeutic degradation. Bacterial cells were previously explored as vectors for biologic delivery, yet cellular engineering approaches have traditionally lowered fitness and colonization potential of these microbial factories. As a result, recombinant bacteria are often outcompeted by the native gut flora, requiring high concentrations to alleviate disease pathology. These limitations support the need for novel mechanisms of treatment that improve oral delivery compliance and ease of use. Through the research described in this dissertation, we outline the potential to use bacteriophage as an alternative chassis for biologic production and delivery to the gastrointestinal tract, targeting and reducing symptoms of obesity and ulcerative colitis. Elucidation of this system presents a universal platform for the long-term amelioration of gastrointestinal disease through the use of lytic phage particles.","abstract_has_math":false,"creators":["Baker, Zachary Robert"],"institution":"Virginia Tech","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Biological Sciences","degree_department":"Biological Sciences","school":null,"contributors":[],"advisors":[],"committee_chairs":["Hsu, Bryan"],"committee_members":["Stevens, Ann M.","Caswell, Clayton Christopher","Li, Liwu"],"year":2025,"date_issued":"2025-05-13","date_published":"2025-05-13","updated_at":"2026-07-22T22:20:02Z","subjects":["Bacteriophage","Intestinal microbiome","Drug delivery","Phage engineering","Obesity","Inflammatory Bowel Disease"],"languages":["en"],"rights":["Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International"],"rights_urls":["http://creativecommons.org/licenses/by-nc-nd/4.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:43391"],"render_values":[{"text":"vt_gsexam:43391","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10919/132452","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Hsu, Bryan"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Stevens, Ann M.","Caswell, Clayton Christopher","Li, Liwu"]},{"key":"dc:contributor.department","label":"Department","values":["Biological Sciences"]},{"key":"dc:creator","label":"Author","values":["Baker, Zachary Robert"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-05-14T08:01:07Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-05-14T08:01:07Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-05-13"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biological Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Bacteriophage","Intestinal microbiome","Drug delivery","Phage engineering","Obesity","Inflammatory Bowel Disease"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-nd/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:43391"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10919/132452"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["Current treatments of gastrointestinal (gut) disease are limited by high dosing frequency, patient noncompliance, and complications circumventing the harsh conditions of the upper gastrointestinal tract (e.g. stomach), leading to therapeutic degradation. Bacterial cells were previously explored as vectors for biologic delivery, yet cellular engineering approaches have traditionally lowered fitness and colonization potential of these microbial factories. As a result, recombinant bacteria are often outcompeted by the native gut flora, requiring high concentrations to alleviate disease pathology. These limitations support the need for novel mechanisms of treatment that improve oral delivery compliance and ease of use. Through the research described in this dissertation, we outline the potential to use bacteriophage as an alternative chassis for biologic production and delivery to the gastrointestinal tract, targeting and reducing symptoms of obesity and ulcerative colitis. 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