{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:07:33Z","timestamp":1788934053277,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Antibiotic prophylaxis alters the gut microbiome, potentially expanding antimicrobial resistance genes (ARGs). The role of bacteriophages in this process remains poorly understood. This study investigates the effects of predominantly flucloxacillin- and gentamicin-based perioperative antibiotic prophylaxis on phage and ARG dynamics in orthopedic trauma patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Shotgun metagenomic analysis in two orthopedic cohorts: rib fracture fixation (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f16) and frail hip fracture fixation (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f22), versus frail (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f18) and non-frail (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f95) controls was performed. Phage abundance (viral sequence groups [VSGs] relative abundance) was quantified using MetaPhlAn 4.1, while ARG abundance using ResFinder 7 (v2022) with KMA (v2.3.0). ViroProfiler with CheckV for quality assessment was used to detect ARG-carrying viral contigs in antibiotic-treated patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following antibiotics, seven VSGs were increased in rib and five in the frail hip fractures compared to controls (mean Log\u2082 Fold change: 16.89 and 17.21, respectively). In the frail cohort, 18 ARGs increased, including 14 off-target ARGs (resistance genes for antibiotics not administered; mean Log\u2082 Fold change &amp;gt;25 compared to controls). Five VSGs correlated with six off-target ARGs in antibiotic-treated patients (Rho\u202f=\u202f0.612). Longitudinal analysis of rib fracture patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f10) revealed off-target ARGs increased from discharge to follow-up, paralleling increased VSGs abundances, while on-target ARGs remained mostly stable. In antibiotic-treated compared to controls, phage-related and DNA-repair gene families were enriched, phage gene richness was associated with stress and biofilm formation pathways, and VSGs correlated with opportunistic species (e.g.,\n                      <jats:italic>E. coli<\/jats:italic>\n                      ). More frail antibiotic-exposed patients (81.5%) carried ARG-containing viral contigs than non-frail patients (41.4%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings suggest perioperative antibiotics may contribute to phage-associated dissemination of off-target ARGs. Understanding how ARGs spread in the gut microbiome is important for improving antibiotic stewardship and protecting vulnerable patients from difficult to treat infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1892653","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:57:13Z","timestamp":1788933433000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut phages are linked to off-target antimicrobial resistance genes in orthopedic patients receiving peri-surgical antibiotics"],"prefix":"10.3389","volume":"17","author":[{"given":"Afroditi","family":"Kouraki","sequence":"first","affiliation":[{"name":"NIHR Nottingham Biomedical Research Centre, Queens Medical Centre","place":["Nottingham, United Kingdom"]},{"name":"Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham","place":["Nottingham, United 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