Over the past decades the aquaculture sector has seen a tremendous growth and intensification in order to meet the growing global demand for animal proteins. This intensification came with a cost as it resulted in an increase in disease incidences due to several factors. A common countermeasure for the increased disease incidence is the use of antibiotics. β-glucans are a waste product and can be used to improve immune functioning in aquaculture fish. Optimal use of β-glucans might reduce the need for antibiotic usage in aquaculture. In this thesis we describe the different approaches we have used to investigate the mechanism through which β-glucan-supplementation modulates the immune system of carp. We have investigated the induction of trained immunity by pre-exposing common carp primary macrophages to β-glucans and looking at longer lived effects. Furthermore, we have looked at the effects of β-glucans after oral administration on the intestinal gene expression and on the intestinal microbiota. Interestingly, we showed that the intestinal microbiota of naive carp was able to ferment β-glucans which resulted in specific profiles in fermentation end products, short chain fatty acids. The third approach that we have taken was whole transcriptome analysis of primary macrophages stimulated with β-glucans in vitro. This approach resulted in a large dataset with significantly regulated genes, providing a valuable asset for future studies. The diverse angles of approach taken in the studies in this thesis have allowed a better understanding of the underlying mechanisms possibly explaining effects of β-glucan supplementation in common carp. This improved understanding of β-glucan induced immuno-modulation will provide a strong base for future studies. In the long-term, the findings in this thesis might aid in achieving concepts such as “personalized feeding”, similar to “personalized nutrition”. Fish health could be improved through these optimized feeding strategies and reduce the need to employ other measures to improve health, such as antibiotics or vaccination strategies.