{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:43:59Z","timestamp":1790613839045,"version":"4.1.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the norwegian seafood research fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The aim of this study was to evaluate the potential of diatom (microalgae) biomass as a lice-reducing ingredient in salmon feed. The original hypothesis was based on the fact that polyunsaturated aldehydes (PUAs), e.g. 2-trans, 4-trans decadenial (A3) produced by diatoms can function as grazing deterrents and harm copepod development. Salmon lice (<jats:italic>Lepeophtheirus salmonis<\/jats:italic>) is a copepod, and we intended to test if inclusion of diatom biomass in the feed could reduce the infestation of lice on salmon. We performed experiments where salmon kept in tanks were offered four different diets, i.e. basic feed with diatoms, fish oil,<jats:italic>Calanus<\/jats:italic>sp. oil or rapeseed oil added. After a feeding period of 67 days a statistically representative group of fishes, tagged with diet group origin, were pooled in a 4000L tank and exposed to salmon lice copepodites whereafter lice infestation was enumerated. Salmon from all four diet groups had good growth with SGR values from 1.29 to 1.44% day<jats:sup>-1<\/jats:sup>(increase from ca. 130 g to 350 g). At the termination of the experiment the number of lice on salmon offered diatom feed were statistically significantly lower than on salmon fed the other diets. Mean lice infestation values increased from diatom feed through<jats:italic>Calanus<\/jats:italic>and fish oil to standard feed with terrestrial plant ingredients. Analysis of the chemical composition of the different diets (fatty acids, amino acids) failed to explain the differences in lice infestation. The only notable result was that diatom and<jats:italic>Calanus<\/jats:italic>feed contained more FFA (free fatty acids) than feed with fish oil and the control feed. None of the potential deleterious targeted polyunsaturated aldehydes could be detected in skin samples of the salmon. What was exclusive for salmon that experienced reduced lice was diatom inclusion in the feed. This therefore still indicates the presence of some lice deterring ingredient, either in the feed, or an ingredient can have triggered production of an deterrent in the fish. An obvious follow up of this will be to perform experiments with different degrees of diatom inclusion in the feeds, i.e. dose response experiments combined with targeted PUA analyses, as well as to perform large scale experiments under natural conditions in aquaculture pens.<\/jats:p>","DOI":"10.1371\/journal.pone.0255370","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T18:46:20Z","timestamp":1627584380000},"page":"e0255370","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inclusion of photoautotrophic cultivated diatom biomass in salmon feed can deter lice"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-5878","authenticated-orcid":true,"given":"Hans Chr.","family":"Eilertsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edel","family":"Elvevoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg Hulda","family":"Gi\u00e6ver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon Brage","family":"Svenning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Dalheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnhild Aven","family":"Svalheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birthe","family":"Vang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sten","family":"Siikavuopio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnhild","family":"Drag\u00f8y","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2871-8888","authenticated-orcid":true,"given":"Richard A.","family":"Ingebrigtsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Espen","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Hustad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-7188","authenticated-orcid":true,"given":"Karl-Erik","family":"Eilertsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"issue":"3","key":"pone.0255370.ref001","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/10641262.2011.597890","article-title":"Atlantic salmon (Salmo salar): the \u201csuper-chicken\u201d of the sea?","volume":"19","author":"O Torrissen","year":"2011","journal-title":"Rev Fish Sci"},{"issue":"1737","key":"pone.0255370.ref002","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1098\/rspb.2012.0084","article-title":"Sea lice as a density-dependent constraint to salmonid farming","volume":"279","author":"PA Jansen","year":"2012","journal-title":"Proceedings of the Royal Society B: Biological Sciences"},{"key":"pone.0255370.ref003","doi-asserted-by":"crossref","first-page":"102061","DOI":"10.1016\/j.aquaeng.2020.102061","article-title":"Prediction of size-dependent risk of salmon smolt (Salmo salar) escape through fish farm nets","volume":"89","author":"M Sistiaga","year":"2020","journal-title":"Aquacult Eng"},{"issue":"6","key":"pone.0255370.ref004","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1111\/j.1095-8649.1996.tb01813.x","article-title":"The physiological effects of salmon lice infection on post\u2010smolt of Atlantic salmon","volume":"48","author":"A Grimnes","year":"1996","journal-title":"J Fish Biol"},{"issue":"4","key":"pone.0255370.ref005","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1111\/raq.12299","article-title":"Salmon lice treatments and salmon mortality in Norwegian aquaculture: a review","volume":"11","author":"K Overton","year":"2019","journal-title":"Reviews in Aquaculture"},{"issue":"10\u201311","key":"pone.0255370.ref006","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.ijpara.2019.12.005","article-title":"Effect of cleaner fish on sea lice in Norwegian salmon aquaculture: a national scale data analysis","volume":"50","author":"LT Barrett","year":"2020","journal-title":"Int J Parasitol"},{"key":"pone.0255370.ref007","unstructured":"Kaldheim O, Nordbotn S. 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Degerlund","year":"2010","journal-title":"Estuar Coast"},{"issue":"3","key":"pone.0255370.ref020","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3390\/md7030367","article-title":"The influence of bioactive oxylipins from marine diatoms on invertebrate reproduction and development","volume":"7","author":"GS Caldwell","year":"2009","journal-title":"Mar Drugs"},{"issue":"3","key":"pone.0255370.ref021","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3856\/vol39-issue3-fulltext-5","article-title":"Effect of polyunsatured aldehyde (A3) as an antiparasitary ingredient of Caligus rogercresseyi in the feed of Atlantic salmon, Salmo salar","volume":"39","author":"J Troncoso","year":"2011","journal-title":"Latin American Journal of Aquatic Research"},{"issue":"8","key":"pone.0255370.ref022","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1111\/are.13729","article-title":"Ultrasound as potential inhibitor of salmon louse infestation\u2014A small\u2010scale 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natures","volume":"56","author":"E Cequier-S\u00e1nchez","year":"2008","journal-title":"J Agric Food Chem"},{"issue":"2","key":"pone.0255370.ref026","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1021\/ac60146a047","article-title":"Analysis of long-chain fatty acids by gas-liquid chromatography","volume":"31","author":"W Stoffel","year":"1959","journal-title":"Analytical Chemistry"},{"key":"pone.0255370.ref027","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.algal.2018.10.009","article-title":"Temperature dependent growth rate, lipid content and fatty acid composition of the marine cold-water diatom Porosira glacialis","volume":"37","author":"JB Svenning","year":"2019","journal-title":"Algal Research"},{"key":"pone.0255370.ref028","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.chroma.2017.07.063","article-title":"Optimization of normal phase chromatographic conditions for lipid analysis and comparison of associated detection techniques","volume":"1514","author":"S Abreu","year":"2017","journal-title":"J Chromatogr"},{"key":"pone.0255370.ref029","author":"S Moore","year":"1963","journal-title":"Chromatographic determination of amino acids by the use of automatic recording equipment"},{"issue":"3","key":"pone.0255370.ref030","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1365-2095.2012.00960.x","article-title":"Nutrient evaluation of rotifers and zooplankton: feed for marine fish larvae","volume":"19","author":"H M\u00e6hre","year":"2013","journal-title":"Aquacult Nutr"},{"key":"pone.0255370.ref031","volume-title":"Diet, nutrition, and the prevention of chronic diseases: report of a joint WHO\/FAO expert consultation","author":"WHO\/FAO","year":"2003"},{"key":"pone.0255370.ref032","unstructured":"Team RC. R: A language and environment for statistical computing. Vienna, Austria; 2020. 2020."},{"key":"pone.0255370.ref033","volume-title":"Package \u2018car\u2019","author":"J Fox","year":"2012"},{"key":"pone.0255370.ref034","volume-title":"R function for performing Games-Howell Post-Hoc Test","author":"A Schlegel","year":"2016"},{"key":"pone.0255370.ref035","doi-asserted-by":"crossref","first-page":"817","DOI":"10.2307\/1912934","article-title":"A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity","author":"H White","year":"1980","journal-title":"Econometrica: journal of the Econometric Society"},{"issue":"3","key":"pone.0255370.ref036","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/00031305.2000.10474549","article-title":"Using heteroscedasticity consistent standard errors in the linear regression model","volume":"54","author":"JS Long","year":"2000","journal-title":"The American 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upon marine ingredients in diets for farmed Atlantic salmon (Salmo salar L.)","volume":"314","author":"E\u00c5 Bendiksen","year":"2011","journal-title":"Aquaculture"},{"issue":"9","key":"pone.0255370.ref041","doi-asserted-by":"crossref","first-page":"e0198538","DOI":"10.1371\/journal.pone.0198538","article-title":"Minimizing marine ingredients in diets of farmed Atlantic salmon (Salmo salar): effects on growth performance and muscle lipid and fatty acid composition","volume":"13","author":"M Beheshti Foroutani","year":"2018","journal-title":"PloS one"},{"issue":"1\u20134","key":"pone.0255370.ref042","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.aquaculture.2010.05.021","article-title":"Growth, flesh adiposity and fatty acid composition of Atlantic salmon (Salmo salar) families with contrasting flesh adiposity: Effects of replacement of dietary fish oil with vegetable oils","volume":"306","author":"JG Bell","year":"2010","journal-title":"Aquaculture"},{"issue":"3","key":"pone.0255370.ref043","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1365-2095.2004.00289.x","article-title":"Replacing dietary fish oil with increasing levels of rapeseed oil and olive oil\u2013effects on Atlantic salmon (Salmo salar L.) tissue and lipoprotein lipid composition and lipogenic enzyme activities","volume":"10","author":"B Torstensen","year":"2004","journal-title":"Aquacult Nutr"},{"issue":"26","key":"pone.0255370.ref044","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1021\/jf051308i","article-title":"Tailoring of Atlantic salmon (Salmo salar L.) flesh lipid composition and sensory quality by replacing fish oil with a vegetable oil blend","volume":"53","author":"BE Torstensen","year":"2005","journal-title":"J Agric Food 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