Microbiome-directed dietary interventions such as microbiota-directed fibers (MDFs) have a proven track record in eliciting responses in beneficial gut microbes and are increasingly being promoted as an effective strategy to improve animal production systems. Here we used initial metataxonomic data on fish gut microbiomes as well as a wealth of a priori mammalian microbiome knowledge on α-MOS and β-mannan-derived MDFs to study effects of such feed supplements in Atlantic salmon (Salmo salar) and their hitherto poorly characterized gut microbiomes. Our multi-omic analysis revealed that the investigated MDFs (two α-mannans and an acetylated β-galactoglucomannan), at a dose of 0.2%, had negligible effects on both host gene expression, and gut microbiome structure and function under studied conditions. While a subsequent trial using a higher (4%) dietary inclusion of β-mannan significantly shifted the gut microbiome composition, there were still no biologically relevant effects on salmon metabolism and physiology. Only a singleBurkholderia-Caballeronia-Paraburkholderia(BCP) population demonstrated consistent and significant abundance shifts across both feeding trials, although with no evidence of β-mannan utilization capabilities or changes in gene transcripts for producing metabolites beneficial to the host. In light of these findings, we revisited our omics data to predict and outline novel and potentially beneficial endogenous lactic acid bacteria that should be targeted with future, conceivably more suitable, MDF strategies for salmon.IMPORTANCEThis study focuses on the potential of MDFs to improve aquaculture production. Despite preliminary 16S rRNA amplicon data suggested that populations in the salmon gut microbiome could utilize structurally complex mannans, our findings indicates that endogenous microbes could not metabolize it, nor the host responds to its dietary inclusion, at least not under the trial conditions investigated in this study. We highlight that high-resolution and host-specific microbiome characterization can greatly improve trial design and selection of candidate MDFs for future nutritional interventions. Understanding the intricate interplay between host and its gut microbiome is paramount in studies seeking to leverage endogenous microbial communities to benefit the host. While each new condition, whether it is a disease onset or a nutritional stressor, has the potential to profoundly reshape the microbial diversity, composition and outputs, the functional microbiome information gained under healthy conditions represent a pivotal step towards designing more effective trials involving microbiome-reprogramming feed additives. Overall, we envisage that these results will lead to improved focus on coupling fundamental microbiome characterization to the design of next-generation feeds for salmon aquaculture.