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By using zebrafish (Danio rerio) as a sentinel species, this study investigated the effects of subchronic 5 mg\/L TiO2-NP exposure. Dynamic light scattering was utilized to characterize the bimodal aggregates (peaks at 917 and 46,841 nm; surface charge: +22.08 mV) that define the environmental state of TiO2-NPs. Parallel 16S rRNA metagenomic profiling on Day 6, prior to mortality, revealed profound gut dysbiosis. A marked increase in Chao1 richness (p &lt; 0.01), alongside a catastrophic 333-fold reduction in beneficial Cetobacterium and an 856-fold enrichment of pathogenic Mycobacterium, was observed. Beta-diversity and hierarchical clustering analyses revealed a striking convergence between gut and gill microbial signatures, supporting a gut-to-gill translocation model. These results suggest that TiO2-NPs exposure induces intestinal dysbiosis, facilitating opportunistic bacterial migration via internal (gut\u2013blood\u2013gill) or external (fecal\u2013water\u2013gill) pathways. This study identifies dysbiosis-driven secondary infection as a novel, overlooked mechanism of nanoparticle toxicity, necessitating a shift in ecological risk assessments toward host\u2013microbe interactions.<\/jats:p>","DOI":"10.3390\/ijms27115036","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:38:42Z","timestamp":1780411122000},"page":"5036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TiO2 Nanoparticles Trigger Gut-to-Gill Bacterial Translocation and Dysbiosis in Zebrafish"],"prefix":"10.3390","volume":"27","author":[{"given":"Chi-Cheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, 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