2 17 Microbial ingredients such as Candida utilis yeast are known to be functional protein sources with 18 immunemodulating effects whereas soybean meal causes soybean meal-induced enteritis in the distal 19 intestine of Atlantic salmon (Salmo salar L.). Inflammatory or immunomodulatory stimuli at the local 20 level in the intestine may alter the plasma proteome profile of Atlantic salmon. These deviations can 21 be helpful indicators for fish health and therefore potential tools in diagnosis of fish diseases. The 22 present work aimed to identify local intestinal tissue responses and changes in plasma protein profiles 23 of Atlantic salmon fed inactive dry Candida utilis yeast biomass, soybean meal, or combination of 24 soybean meal based diet with various inclusion levels of Candida utilis. A fishmeal based diet was 25 used as control diet. Inclusion of Candida utilis yeast to a fishmeal based diet did not alter the 26 morphology, immune cell population or gene expression of the distal intestine, but gave a plasma 27 proteome profile different from the fishmeal based control. Lower levels of Candida utilis combined 28 with soybean meal modulated immune cell populations in the distal intestine and reduced the severity 29 of soybean meal-induced enteritis, while higher inclusion levels of Candida utilis were less effective. 30 The results suggest that Candida utilis could induce systemic responses without altering intestinal 31 morphology, and thus could be a high-quality alternative protein source with potential functional 32 properties in diets for Atlantic salmon.33 Introduction 34 The composition of feeds used in salmon aquaculture has undergone significant changes over the last 35 decades. The rapid growth in the aquaculture industry, but stable production of the major protein 36 resource, fishmeal (FM), has led to increasing use of alternatives. Alternative protein sources are 37 required to contribute to a well-balanced diet and to support optimal fish growth performance, health 38 and disease resistance. Currently, proteins derived from insects [1], terrestrial animal co-products [2, 3 39 3] and microbial ingredients [4] are considered to be valuable alternatives. In commercial diets, plant 40 derived proteins have already replaced two third of the proteins of marine origin [5].41 Plant ingredients are the most attractive protein sources due to their low cost of production, high protein 42 content and availability [6]. Inclusion of plant ingredients in salmonid feeds can, however, result in 43 reduced growth performance and feed utilization, and health issues due to anti-nutritional factors 44 (ANF) [6, 7]. ANFs in plant-based diets have been associated with detrimental effects on the intestine 45 of several salmonid species [7], and soybean meal-induced enteritis (SBMIE) is a well described 46 condition in Atlantic salmon (Salmo salar L.) [8, 9]. Currently, in commercial salmon diets, the refined 47 soy product with reduced level of ANF, soy protein concentrate, is the major protein source of plant ...