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Translocation of nasopharynx-resident opportunistic pathogens like nontypeable<jats:italic>Haemophilus influenzae<\/jats:italic>(NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts (<jats:italic>n<\/jats:italic>\u2009=\u20093\/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) and reductions in alpha diversity (<jats:italic>q<\/jats:italic>\u2009&lt;\u20090.20) relative to baseline, mAb antibodies failed to affect diversity, indicating maintenance of a eubiotic state. Taxonomic and longitudinal analyses showed blooms in opportunistic pathogens (ANCOM) and greater magnitudes of compositional change (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) following broad-spectrum antibiotic but not mAb treatments. Collectively, results showed broad-spectrum antibiotics induced significant fecal and nasopharyngeal microbiome disruption regardless of delivery route. Excitingly, biofilm-targeting antibodies had little effect on fecal and nasopharyngeal microbiomes.<\/jats:p>","DOI":"10.1038\/s41522-024-00481-0","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T10:02:14Z","timestamp":1706954534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oral and middle ear delivery of otitis media standard of care antibiotics, but not biofilm-targeted antibodies, alter chinchilla nasopharyngeal and fecal microbiomes"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4825-2915","authenticated-orcid":false,"given":"Audrey F.","family":"Duff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Jurcisek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"Kurbatfinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tendy","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven D.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0017-1710","authenticated-orcid":false,"given":"Lauren O.","family":"Bakaletz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2222-3980","authenticated-orcid":false,"given":"Michael T.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,3]]},"reference":[{"key":"481_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-016-0638-2","volume":"16","author":"V Usonis","year":"2016","unstructured":"Usonis, V. et al. 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