{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:10:18Z","timestamp":1776831018966,"version":"3.51.2"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M732476"],"award-info":[{"award-number":["2023M732476"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Project of Sichuan Provincial Key Laboratory of Fish Resources Conservation and Utilization in the Upper Reaches of the Yangtze River","award":["NJTCSC24-3"],"award-info":[{"award-number":["NJTCSC24-3"]}]},{"name":"Sichuan Science and Technology Program","award":["2023YFH0046"],"award-info":[{"award-number":["2023YFH0046"]}]},{"name":"Yancheng City Key R&D Program (Industrial) Projects","award":["BE2023026"],"award-info":[{"award-number":["BE2023026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Ichthyophthirius multifiliis poses a significant threat to global aquaculture, yet some fish species exhibit remarkable resistance. This study employed a combined LC-MS-based metabolomics and 16S rRNA gene sequencing approach to investigate the intrinsic mechanisms underlying the differential susceptibility of Percocypris pingi, crucian carp, and yellow catfish. Our results revealed distinct skin molecular and microbial profiles in P. pingi associated with its enhanced resilience. Metabolomic analysis identified a significant upregulation of key antioxidants (L-Glutathione reduced, L-Glutathione oxidized, L-Cysteine-glutathione gisulfide, Uric acid, Histamine, N-Acetylhistamine, and scorbic acid) in P. pingi, most notably L-Glutathione reduced, which was 31- and 59-fold higher than in yellow catfish and crucian carp, respectively. Functional enrichment further highlighted the critical role of enhanced antioxidant capacity (centered on glutathione metabolism) and immune\/inflammatory responses in the resistance to I. multifiliis of P. pingi. Concurrently, skin microbiome analysis showed that P. pingi hosted a microbial community distinct from the other two species, with significantly higher \u03b1-diversity. Notably, P. pingi skin was significantly depleted of the parasitic bacteria Candidatus_Megaira and Candidatus_Midichloria, which were highly abundant in the susceptible species. Furthermore, predicted metagenomic functions indicated that P. pingi\u2019s microbiota was enriched in fundamental metabolic pathways, whereas the microbiota of crucian carp and yellow catfish was skewed towards disease- and immune-related pathways. In conclusion, our findings demonstrate that the superior resistance of P. pingi to I. multifiliis is likely conferred by a synergistic effect of a robust skin antioxidant capacity (primarily driven by glutathione) and a protective skin microbiome that excludes specific parasites. This study provides novel insights into the multi-faceted mechanisms of disease resistance in fish.<\/jats:p>","DOI":"10.3390\/biology14111546","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T12:13:08Z","timestamp":1762258388000},"page":"1546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolome and Metagenome Signatures Underlying the Differential Resistance of Percocypris pingi, Crucian Carp, and Yellow Catfish to Ichthyophthirius multifiliis Infection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2664-1055","authenticated-orcid":false,"given":"Yi","family":"Liu","sequence":"first","affiliation":[{"name":"Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, College of Fisheries, Neijiang Normal University, Neijiang 641100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, College of Fisheries, Neijiang Normal University, Neijiang 641100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2880-2008","authenticated-orcid":false,"given":"Yang","family":"He","sequence":"additional","affiliation":[{"name":"Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, College of Fisheries, Neijiang Normal University, Neijiang 641100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingchao","family":"Shi","sequence":"additional","affiliation":[{"name":"Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, College of Fisheries, Neijiang Normal University, Neijiang 641100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quan","family":"Gong","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8422-9723","authenticated-orcid":false,"given":"Weihong","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Marine and Bioengineering, Yancheng Institute of Technology, Yancheng 224051, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanjie","family":"Qin","sequence":"additional","affiliation":[{"name":"Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, College of Fisheries, Neijiang Normal University, Neijiang 641100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-5459","authenticated-orcid":false,"given":"Chuang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China"},{"name":"Observation and Research Station of Sichuan Province of Fish Resources and Environment in Upper Reaches of the Yangtze River, College of Life Sciences, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","unstructured":"Dickerson, H.W. 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