Identification of Association Between Mucus Microbiota and Gene Expression in the Gill of a Streptococcus agalactiae-Resistant Nile Tilapia Strain Though Multi-Omics Analyses

Streptococcus agalactiae infections severely threaten global tilapia aquaculture, causing substantial mortality and economic damage. The “Zhuangluo 1” (ZL) strain, derived from the fast-growing GIFT Nile tilapia and refined through multiple generations of selection, uniquely combines robust resistance to S. agalactiae with improved growth traits. This study examined gene expression and regulation of gill mucus microbiota in ZL during experimental S. agalactiae challenge. 16S rRNA sequencing revealed Flavobacterium, Vogesella, Hydrogenophaga, Acidovorax, Rheinheimera, and Deinococcus as prominent genera in the gill mucus microbiome of ZL across time points. Transcriptome time-course analysis identified differentially expressed genes in gills of ZL that were predominantly enriched in cytoskeleton in muscle cells and motor protein pathways. Abundances of the dominant genera Flavobacterium and Hydrogenophaga showed significant correlations with genes regulating mucus secretion, mucin glycosylation, immune modulation, and oxidative stress response in ZL. Untargeted metabolomics of gill mucus revealed substantially higher levels of metabolites potentially linked to microbial metabolism and host–microbiota interactions in ZL. A complementary genome-wide association study for resistance in ZL further localized genes underlying these expression–microbiota associations. These findings elucidated microbiota–host interactions between ZL and gill mucus microbiota, and provide more insights into the role of mucus regulation in disease resistance.