LAUSR

Abstract The aim of this study was to evaluate the impact of fish meal (FM) and fish oil (FO) replacement by plant proteins and oils in the serum metabolome of two-year old gilthead sea bream (Sparus aurata) fed from early life stages with control and experimental diets. Randomly selected fish were overnight sampled and clotted serum was used for metabolomics fingerprinting by means of ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. >12,500 different m/z ions were detected, and Partial Least Squares-Discriminant analysis separated fish fed control and plant-based diets, with a 71% of variance explained and 44% of variance predicted by the two first components. After variable importance in projection (VIP) and Benjamini-Hochberg test correction filtering, 50 endogenous compounds were elucidated as highly discriminant features of dietary treatment. Most of them were lipid-related compounds and reflected the different fatty acid composition of dietary oils, whereas changes in N-acyl taurines, cytidine and nucleoside related compounds would indicate changes in tissue repair and DNA degradation processes. Untargeted analysis also identified some exogenous compounds as markers of marine and vegetable raw materials. In the case of hercynine (antioxidant fungi and mycobacteria product), this was exemplified by a close lineal association between circulating and feed levels. Targeted approaches were focused on vitamins and a clear reduction of B12, indirectly assessed via methylmalonic acid levels, was found in fish fed vegetable diets. Conversely, serum riboflavin (B2) and pantothenic acid (B5) levels were consistently increased, which highlighted the close link between nutrition and gut microbiota.