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Nisin Z also showed promising activity against various cancer types\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and significantly reduced tumor size in an ectopic head and neck cancer model. Here, we investigate the activity of nisin Z for colorectal cancer treatment and observed an\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      reduction in cellular proliferation and a moderate enhancement in cell death. We next analyzed the effect of oral nisin Z administration in the Apc\n                      <jats:sup>Min\/+<\/jats:sup>\n                      intestinal adenoma mouse model. We measured tumor burden along the gastrointestinal tract and observed a decrease in tumor burden in the middle region of the small intestine but not in the lower region or colon. Since tumor progression in the Apc\n                      <jats:sup>Min\/+<\/jats:sup>\n                      model is exacerbated by an inflammatory environment, we next determined whether nisin Z impacts this in a direct or indirect manner. We show that nisin Z directly reduces NF-\u03baB activation in a dose-dependent manner in a cell-based assay, and we observe a corresponding reduction in NF-\u03baB protein expression in the middle region of the small intestine. In addition, nisin Z impacted the cecal microbiome composition as well as microbiota-associated plasma metabolites, leading to changes that are in part associated with beneficial outcomes. Interestingly, the Apc\n                      <jats:sup>Min\/+<\/jats:sup>\n                      genotype differentially impacted the nisin Z-mediated differences in cecal microbiome composition and plasma metabolites compared to wild-type animals. In summary, our data suggest that the reduction in small intestinal tumor burden could be due to nisin Z\u2019s contribution to a reduced pro-inflammatory environment. Future studies will reveal whether nisin\u2019s localized effect is due to degradation of the peptidic compound in more distal regions of the gastrointestinal tract and focus on development of delivery systems to increase efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      With the increased incidence of colorectal cancer, especially among younger individuals, it is critical to study approaches that help with the prevention and treatment of this debilitating disease. Our study indicates that nisin Z, a bacterially produced peptide antibiotic, decreases the growth of colorectal cancer cells and moderately increases cell death\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Oral administration of nisin Z in an intestinal adenoma mouse model revealed a reduction of tumor burden in the middle region of the small intestine. This decreased tumor burden might in part be attributed to a direct anti-inflammatory effect, as well as an indirect effect on the gut microbiota and their metabolites due to nisin Z\u2019s antibacterial activity. Overall, we demonstrate a potential activity for nisin Z in the prevention or amelioration of inflammation-associated colorectal cancer, underscoring the significance of investigating the properties of bacterial natural products in human health.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01557-25","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:14:24Z","timestamp":1759756464000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["The antimicrobial metabolite nisin Z reduces intestinal tumorigenesis and modulates the cecal microbiome in Apc\n                    <sup>Min\/+<\/sup>\n                    mice"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9566-5491","authenticated-orcid":true,"given":"Layan","family":"Hamidi 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