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This study aimed to investigate the short\u2010term effects of antibiotics on the sinus and gut microbiota as well as any relationships these had with drug distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty subjects undergoing functional endoscopic sinus surgery for CRS were randomized to one of three groups: (1) doxycycline (100\u00a0mg daily for 7 days); (2) roxithromycin (300\u00a0mg daily for 7 days); and (3) control (no antibiotics given). Sinonasal and stool samples collected before and after treatment were analyzed using 16S ribosomal RNA (rRNA) gene\u2010targeted amplicon sequencing and Droplet Digital polymerase chain reaction (PCR) for bacterial community composition and the quantification of bacterial DNA, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no significant major bacterial community shifts or changes to bacterial diversity and load following the treatment period in all patient groups. Non\u2010significant trend reductions were observed in gut microbial diversity with antibiotics. For the roxithromycin group, sinonasal bacterial diversity was negatively correlated with serum drug levels and reduced overall compared to controls (<jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.05). The relative abundance of <jats:italic>Staphylococcus<\/jats:italic> ASV129 in sinonasal samples reduced with increasing mucus doxycycline levels (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Antibiotic prescription for CRS should be further investigated because of preliminary evidence of poor sinonasal drug penetration, unproven efficacy, and the potential impact of dysbiosis in the sinuses and off\u2010target sites. Further studies should consider distinguishing the presence of DNA from viable and nonviable bacteria.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22799","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T04:09:35Z","timestamp":1618978175000},"page":"1355-1366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sinonasal and gastrointestinal bacterial composition and abundance are stable after 1 week of once\u2010daily oral antibiotic treatment for chronic rhinosinusitis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6172-3497","authenticated-orcid":false,"given":"Joey","family":"Siu","sequence":"first","affiliation":[{"name":"Department of Surgery University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett 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