Dual-omics links host genomic variation to gut microbiome restructuring under Mycobacterium marinum challenge in...

Disease outbreaks caused by Mycobacterium marinum pose a major challenge to marine aquaculture and threaten the sustainable production of Cynoglossus semilaevis. Increasing evidence suggests that host genetic variation and gut microbial communities may jointly influence disease-related phenotypes, yet their interaction under mycobacterial challenge remains poorly understood. In this study, we combined host whole-genome resequencing and gut 16S rRNA sequencing to explore host-microbiome associations in C. semilaevis following M. marinum challenge. Gut microbiota analysis revealed significant differences in community structure and composition between the experimental and control groups, with marked shifts in dominant taxa and differential enrichment of several bacterial genera. Genome-wide association analysis identified nine significant SNPs (λ = 1.02) associated with infection status, distributed across chromosomes 5, 10, 13, 18, and 19. Functional annotation showed that most of these loci were located in non-coding or regulatory regions, including six intronic SNPs, one ncRNA_exonic SNP, one ncRNA_intronic SNP, and one intergenic SNP. Correlation network analysis further linked host genetic variants with changes in gut microbial taxa, suggesting a potential association between host genomic variation and microbiome restructuring under challenge conditions. Overall, these results provide preliminary evidence that host genomic variation may be associated with gut microbiome dynamics during M. marinum infection in C. semilaevis. Although limited by sample size, this dual-omics framework offers a useful basis for future validation of host-microbiome markers relevant to disease-resilience breeding in aquaculture. CONCLUSION: Host genomic variation in C. semilaevis may be associated with gut microbiome restructuring under M. marinum challenge, particularly involving Acinetobacter dynamics. Although limited by sample size, this dual-omics framework provides a preliminary basis for future disease-resilience breeding in aquaculture.