[{"key":"dc.contributor.author","value":"Larnder, Ashley Heather","language":null},{"key":"dc.date.accessioned","value":"2026-03-20T17:34:47Z","language":null},{"key":"dc.date.available","value":"2026-03-20T17:34:47Z","language":null},{"key":"dc.date.issued","value":"2026","language":"en"},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/93812","language":null},{"key":"dc.description.abstract","value":"Breast cancer is the most common cancer among females, with hormone-receptor\u2013 positive tumors comprising most cases. Growing evidence links the gut microbiome to carcinogenesis, and the estrobolome\u2014a subset of gut microbes involved in estrogen metabolism\u2014has been proposed as a contributor to breast cancer risk. However, specific estrobolome targets and underlying mechanisms remain poorly defined, and few studies integrate microbial, metabolomic, and dietary data to explore these pathways.\r\nThis thesis synthesized findings from three components: 1) a scoping review identified relevant estrobolome features from mechanistic and experimental evidence in the literature; 2) a case\u2013control study of newly diagnosed postmenopausal breast cancer in Canada used whole- metagenome shotgun sequencing and plasma and stool metabolomics at baseline and 6-months to both compare baseline case\u2013control differences and to evaluate within-person changes over time; and 3) a case\u2013cohort study of incident breast cancer in France to examine diet and metabolite associations with breast cancer incidence.\r\nThe scoping review showed that estrobolome targets remain incompletely annotated and evidence showing their association to breast cancer is inconsistent. In the case\u2013control study, baseline comparisons revealed no clear differences in estrogens or directly related microbial functions between cases and controls. Instead, case\u2013control differences appeared in the broader hormone environment\u2014including estrogen precursors, downstream metabolites, and phytoestrogens\u2014and beyond hormones, including Alistipes spp., conjugated bile acids, and microbial pathways related to vitamin K2 biosynthesis, TCA-linked energy metabolism, amino acid metabolism, and NAD salvage. Follow-up analyses indicated that many of these same features changed from baseline to six months. The French case\u2013cohort study supported the relevance of glycine-conjugated bile acids and vitamin K pathways and suggested potential diet\u2013 metabolite interactions that may contribute to breast cancer risk.\r\nOverall, this work expands the understanding of breast cancer\u2013associated microbiome and metabolic pathways. Several microbial pathways warrant further mechanistic study and validation, including phytoestrogen metabolism, glycine-conjugated bile acid metabolism, vitamin K2 biosynthesis, TCA-related energy metabolism, amino acid metabolism, and NAD salvage pathways. These findings lay the groundwork for future multi-omics research to clarify microbiome-mediated pathways and evaluate their potential as targets for breast cancer prevention or treatment.","language":"en"},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":"en"},{"key":"dc.rights","value":"Attribution-NonCommercial-NoDerivatives 4.0 International","language":"*"},{"key":"dc.rights.uri","value":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/","language":"*"},{"key":"dc.title","value":"The estrobolome and beyond : microbial and metabolic pathways linking the gut microbiome to female breast cancer","language":"en"},{"key":"dc.type","value":"Text","language":"en"},{"key":"dc.degree.name","value":"Doctor of Philosophy - PhD","language":"en"},{"key":"dc.degree.discipline","value":"Population and Public Health","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":"en"},{"key":"dc.contributor.supervisor","value":"Murphy, Rachel Anne","language":null},{"key":"dc.contributor.supervisor","value":"Manges, Amee R.","language":null},{"key":"dc.date.graduation","value":"2026-05","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Medicine, Faculty of","language":"en"},{"key":"dc.description.affiliation","value":"Population and Public Health (SPPH), School of","language":"en"},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]