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In this study, we evaluated the impact of dietary supplementation with ethanol-inactivated\n                      <jats:italic>V. proteolyticus<\/jats:italic>\n                      DCF12.2 on the intestinal microbiota composition and transcriptomic profile of zebrafish (\n                      <jats:italic>Danio rerio<\/jats:italic>\n                      ). Fish were fed a control diet (CTRL group) or a diet supplemented with 1% lyophilized ethanol-inactivated\n                      <jats:italic>V<\/jats:italic>\n                      .\n                      <jats:italic>proteolyticus<\/jats:italic>\n                      DCF12.2 (VP group) for 21\u00a0days. Alpha and beta diversity analyses exhibited no significant differences in overall gut microbial composition between dietary groups, nor at the phylum or genus level. However, differential abundance analysis at the amplicon sequence variant (ASV) level identified significant differences in ASVs affiliated with the genera\n                      <jats:italic>Aeromonas<\/jats:italic>\n                      ,\n                      <jats:italic>Delftia<\/jats:italic>\n                      ,\n                      <jats:italic>Ralstonia<\/jats:italic>\n                      ,\n                      <jats:italic>Shewanella<\/jats:italic>\n                      , and\n                      <jats:italic>Stenotrophomonas<\/jats:italic>\n                      , which were enriched in fish receiving the VP diet (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Despite these ASV-level shifts, predicted microbial metabolic functions did not differ significantly between treatments. In contrast, transcriptomic analysis via Gene Set Enrichment Analysis (GSEA) detected a clear host response: a significant downregulation of the cytokine\u2013cytokine receptor interaction pathway and the upregulation of pathways related to nutrient metabolism, oxidative phosphorylation, and cellular biosynthesis in fish fed the VP diet (adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). These results suggest that dietary supplementation with postbiotics from\n                      <jats:italic>V. proteolyticus<\/jats:italic>\n                      DCF12.2 modulates intestinal metabolic and immune pathways without inducing major restructuring of the gut microbiota composition. Collectively, these findings provide new insights into host\u2013postbiotic interactions and support the potential application of postbiotics from\n                      <jats:italic>V. proteolyticus<\/jats:italic>\n                      DCF12.2 as functional feed additives for sustainable aquaculture.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      \u2022\u00a0\n                      <jats:italic>Postbiotic diet did not alter gut microbial diversity but induced ASV-level differences<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\u00a0\n                      <jats:italic>Postbiotic diet upregulated nutrient metabolism, oxidative phosphorylation, and cellular biosynthesis<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\u00a0\n                      <jats:italic>Cytokine\u2013cytokine<\/jats:italic>\n                      <jats:italic>receptor signaling was downregulated by the postbiotic diet<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-026-13825-x","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T21:14:36Z","timestamp":1776892476000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vibrio proteolyticus DCF12.2 postbiotic modulates intestinal metabolic and immune pathways in zebrafish"],"prefix":"10.1007","volume":"110","author":[{"given":"Jorge","family":"Garc\u00eda-M\u00e1rquez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Cerezo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Magalh\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f3nio Paulo","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Arijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aires","family":"Oliva-Teles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Mori\u00f1igo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"issue":"6","key":"13825_CR1","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1111\/JPN.13454","volume":"104","author":"ME Abd El-Hack","year":"2020","unstructured":"Abd El-Hack ME, El-Saadony MT, Shafi ME, Qattan SYA, Batiha GE, Khafaga AF, Abdel-Moneim AME, Alagawany M (2020) Probiotics in poultry feed: a comprehensive review. 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