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Currently, antibiotics are the most effective treatment against the causative agent, the bacterium\n                      <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                      . However, the use of antibiotics eventually leads to the emergence of resistant strains, which necessitates the need for alternative approaches. The use of bacteriophages to target the infection by antibiotic-resistant bacteria is one promising alternative. While clearance of\n                      <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                      with the use of phages has been performed on several animal models, none of these models are naturalistic hosts of\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      . Therefore, we set out to investigate the interaction between\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      and bacteriophage ICP1 both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      in a naturalistic host, the zebrafish model,\n                      <jats:italic toggle=\"yes\">Danio rerio<\/jats:italic>\n                      . To study the interplay between host, bacteria, and phages, we used a combination of light and ultrastructural imaging techniques, including confocal fluorescence microscopy, serial block face scanning electron microscopy (EM) imaging, and cryogenic EM, which allowed us to investigate both the colonization process by\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      and clearance by the ICP1 bacteriophage. In addition, we determined the effects of the microbiome on this treatment by using germ-free, conventionalized, and monoassociated zebrafish larvae as a host. Independent of the presence and composition of microbiomes used here,\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      efficiently colonized the larval intestine. Finally, we demonstrate significant\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      clearance of\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      N16961-dsRED by ICP1, underscoring the role of phage-bacteria dynamics in shaping pathogen colonization within the zebrafish larval host.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Cholera remains a life-threatening disease that causes recurring outbreaks and significant mortality, particularly in developing and conflict-affected regions. As antimicrobial resistance continues to rise, there is an urgent need to better understand the ecological and microbial dynamics that govern\n                      <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                      colonization and persistence. This research investigates how\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      interacts with bacteriophages, the host environment, and the resident microbiota within a natural vertebrate host, offering new insights into the factors that influence pathogen clearance and shaping of the gut ecosystem during infection. The powerful combination of serial block-face scanning and cryogenic electron microscopy, fluorescence microscopy, and traditional colony\/plaque counting methods revealed previously unobserved aspects of the interplay between host, pathogen, phages, and selected microsymbionts, highlighting phage-driven clearance of\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      during colonization.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03565-25","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:14:47Z","timestamp":1777900487000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["ICP1 bacteriophage treatment antagonizes colonization of the zebrafish larval intestine by\n                    <i>Vibrio 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