Aquaculture growth is hindered by an increasing number of challenges, primarily infectious diseases and inappropriate or unsustainable fish nutrition. Hence it is critical to develop novel prevention strategies to minimise infectious diseases and pharmaceutical interventions. Nutritional challenges and the health of the fish could be improved by managing their microbial communities. Microbiomes can play a crucial role in fish physiology, particularly in digestion, by metabolizing largely indigestible feed components for the host or synthesis essential micronutrients. Beyond their nutritional role, microbiomes are considered the first line of defence against pathogens. In this study, a novel prebiotic mix (Selectovit), composed of 1,3/1,6-beta glucans, mannan-oligosaccharides, nucleic acids, nucleotides, medium chain fatty acids and single chain fatty acids, was tested at different inclusion levels (0.0; 0.5; 1.0; 2.0 g/kg) in the diet of Atlantic salmon (Salmo salar). Using experimental feed trials and 16S rRNA microbiome profiling, the impact of the prebiotic blend on fish growth and microbial community within both the gastrointestinal tract and the skin was assessed. Overall, the supplement showed no significant impact on growth. However, we clearly demonstrate that the prebiotic can significantly manipulate the microbial community of the distal intestine and the skin. Several potential beneficial bacteria such as Bacillus and Mycoplasma spp. were significantly more abundant in the prebiotic-fed groups compared to the control. In contrast, putative pathogenic bacteria were less abundant in the salmon fed the prebiotic blend. Interestingly, the supplement induced more changes in the skin than in the gut. There is growing evidence in fish for highly complex interactions between the microbial communities of the digestive system and external mucosa, and with the host immune system. Further research in this field could lead to the creation of novel bacterial biomarkers and new non-invasive strategies for fish digestive health monitoring.