DataSheet_1_The Spleen as a Target to Characterize Immunomodulatory Effects of Down-Stream Processed Cyberlindnera jadinii Yeasts in Atlantic Salmon Exposed to a Dietary Soybean Meal Challenge.docx

Aquaculture feeds have changed dramatically from being largely based on fishmeal (FM) towards increased use of plant protein sources, which could impact the fish’s immune response. In order to characterize immunomodulatory properties of novel functional ingredients, this study used four diets, one based on FM, a challenging diet with 40% soybean meal (SBM), and two diets containing 40% SBM with 5% of Cyberlindnera jadinii yeast exposed to different down-stream processing conditions: heat-inactivated (ICJ) or autolysation (ACJ). The immunomodulatory effects of the diets were analyzed in the spleen of Atlantic salmon after 37 days of feeding, using a transcriptomic evaluation by RNA sequencing (RNA-seq) and the detection of specific immunological markers at the protein level through indirect Enzyme-linked Immunosorbent Assay (indirect ELISA). The results showed that SBM (compared to FM) induced a down-regulation of pathways related to ion binding and transport, along with an increase at the protein level of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). On the other hand, while ICJ (compared to FM-group) maintain the inflammatory response associated with SBM, with higher levels of TNFα and IFNγ, and with an upregulation of creatine kinase activity and phosphagen metabolic process, the inclusion of ACJ was able to modulate the response of Atlantic salmon compared to fish fed the SBM-diet by the activation of biological pathways related to endocytosis, Pattern recognition receptor (PPRs)-signal transduction and transporter activity. In addition, ACJ was also able to control the pro-inflammatory profile of SBM, increasing Interleukin 10 (IL-10) levels and decreasing TNFα production, triggering an immune response similar to that of fish fed an FM-based diet. Finally, we suggest that the spleen is a good candidate to characterize the immunomodulatory effects of functional ingredients in Atlantic salmon. Moreover, the inclusion of ACJ in fish diets, with the ability to control inflammatory processes, could be considered in the formulation of sustainable salmon feed.

水产养殖业饲料发生了显著变化，从主要依赖鱼粉（FM）转向增加植物蛋白源的使用，这可能会影响鱼的免疫反应。为了表征新型功能性成分的免疫调节特性，本研究使用了四种饲料，其中一种基于FM，一种挑战性饲料含有40%的大豆粕（SBM），以及两种含有40% SBM且加入5%受不同下游加工条件影响（热失活（ICJ）或自溶（ACJ））的Cyberlindnera jadinii酵母的饲料。在饲养37天后，通过RNA测序（RNA-seq）进行转录组学评估和通过间接酶联免疫吸附测定（indirect ELISA）检测特定的免疫学标记物，分析了这些饲料在太平洋鲑鱼脾脏中的免疫调节效应。结果显示，与FM相比，SBM诱导了与离子结合和转运相关的通路下调，并在蛋白质水平上增加了促炎细胞因子如肿瘤坏死因子α（TNFα）和干扰素γ（IFNγ）的水平。另一方面，与FM组相比，ICJ维持了与SBM相关的炎症反应，TNFα和IFNγ水平更高，且肌酸激酶活性和磷酸化代谢过程上调，而加入ACJ能够通过激活与内吞作用、模式识别受体（PPRs）信号转导和转运活性相关的生物途径，调节与SBM饲料喂养的太平洋鲑鱼相比的免疫反应。此外，ACJ还能控制SBM的促炎表型，提高白细胞介素10（IL-10）水平并降低TNFα的产生，引发与鱼粉基饲料喂养的鱼的类似免疫反应。最后，我们提出，脾脏是表征大西洋鲑鱼功能性成分免疫调节效应的良好候选器官。此外，考虑到ACJ在鱼饲料中的应用能够控制炎症过程，其在可持续鲑鱼饲料配方中的应用值得关注。