Combined transcriptome and metabolome analysis of tilapia response to hypoxia and <scp> <i>Streptococcus agalactiae</i> </scp> co‐exposure

Deterioration of water quality, especially low dissolved oxygen, has contributed to outbreaks of streptococcal disease in tilapia. It has been reported that hypoxia increases the mortality of tilapia during Streptococcus agalactiae infection. However, the underlying mechanism of the increased susceptibility of tilapia to S. agalactiae caused by hypoxia remains unknown. In this study, the pathological effects of hypoxia and S. agalactiae co-exposure in the liver of tilapia were investigated using transcriptome and metabolome analyses. When subjected to individual hypoxia or S. agalactiae exposure, the liver of tilapia exhibited significant pathological effects, including vacuolation, severe necrosis, nuclear and cellular polymorphism, hemocyte infiltration/leakage and abundant granular deposits. Moreover, these pathological effects became more severe under hypoxia and S. agalactiae co-exposure. In addition, S. agalactiae exposure increased inflammation-related gene expression, including CC1, CC2, IL-1β, TNFα, but this effect was suppressed by hypoxia. Transcriptomic analysis revealed that carbohydrate, lipid and amino acid metabolic pathways were significantly altered in the hypoxia and S. agalactiae co-exposure group compared to those in the control group. Among these metabolic pathways, only lipid metabolism was obviously altered at the metabolite level, as revealed by metabolomics analysis. Further combined analysis of the transcriptome and metabolome suggested that, in lipid metabolic pathways, glycerophospholipid metabolism should be a key pathway in S. agalactiae-infected tilapia under hypoxic conditions. Taken together, the results of the combined analysis of the global changes in the transcriptome and metabolome of the tilapia liver under hypoxia and S. agalactiae co-exposure revealed important metabolic pathways involved in the pathological process by which hypoxia increases the susceptibility of tilapia to S. agalactiae.