ERP144394 PRJEB59345 2050a5f4-b28e-46c7-a46a-28b894a780f7 WGBS investigation of DNA methylation associated with tenacibaculosis and gut microbiota composition It remains a challenge to obtain the desired phenotypic traits in aquacultural production of Atlantic salmon, and part of the challenge might come from the effect that host-associated microorganisms have on the fish phenotype. To manipulate the microbiota towards the desired host traits, it is essential to understand the factors that shape it. The bacteria in the surroundings inevitably contribute to the gut microbiota, however, the microbiota composition can also differ completely among fish, even when they are raised in the same closed system. While such microbiota differences can be linked to diseases, it remains elusive how disease affects host-microbiota interactions on a molecular level, and the potential role of epigenetic factors is yet to be described. The aim of this study was to investigate the DNA methylation changes associated with a tenacibaculosis outbreak accompanied by a microbiota displacement in the gut of Atlantic salmon. The genome-wide DNA methylation levels were profiled using Whole Genome Bisulfite Sequencing (WGBS) of the distal gut tissue in 20 salmon and compared between uninfected individuals cohoused and sick fish suffering from tenacibaculosis and microbiota displacement. We discovered more than 19,000 differentially methylated cytosine sites, frequently located in differentially methylated regions and aggregated around genes. The 68 genes overlapping the most significant regions included functions seemingly relevant to the ulcerous disease tenacibaculosis such as epor and slc48a1a. However, the list also included prkcda and a ramp1 ortholog whose functions in model species have been associated with microbiota changes. Combined, our results highlight specific genes potentially involved in host-microbiota interactions, and on a general level they suggest that epigenetic factors should be considered in future efforts aiming to manipulate the microbiota of farmed fish. Intestinal epigenotype of Atlantic salmon (Salmo salar) associates with tenacibaculosis and gut microbiota composition It remains a challenge to obtain the desired phenotypic traits in aquacultural production of Atlantic salmon, and part of the challenge might come from the effect that host-associated microorganisms have on the fish phenotype. To manipulate the microbiota towards the desired host traits, it is essential to understand the factors that shape it. The bacteria in the surroundings inevitably contribute to the gut microbiota, however, the microbiota composition can also differ completely among fish, even when they are raised in the same closed system. While such microbiota differences can be linked to diseases, it remains elusive how disease affects host-microbiota interactions on a molecular level, and the potential role of epigenetic factors is yet to be described. The aim of this study was to investigate the DNA methylation changes associated with a tenacibaculosis outbreak accompanied by a microbiota displacement in the gut of Atlantic salmon. The genome-wide DNA methylation levels were profiled using Whole Genome Bisulfite Sequencing (WGBS) of the distal gut tissue in 20 salmon and compared between uninfected individuals cohoused and sick fish suffering from tenacibaculosis and microbiota displacement. We discovered more than 19,000 differentially methylated cytosine sites, frequently located in differentially methylated regions and aggregated around genes. The 68 genes overlapping the most significant regions included functions seemingly relevant to the ulcerous disease tenacibaculosis such as epor and slc48a1a. However, the list also included prkcda and a ramp1 ortholog whose functions in model species have been associated with microbiota changes. Combined, our results highlight specific genes potentially involved in host-microbiota interactions, and on a general level they suggest that epigenetic factors should be considered in future efforts aiming to manipulate the microbiota of farmed fish. ENA-FIRST-PUBLIC 2023-03-15 ENA-LAST-UPDATE 2023-03-15