Multi-omics reveals the regulatory mechanisms of zinc exposure on the intestine-liver axis of golden pompano Trachinotus ovatus.

Metal zinc (Zn) has been the focus of many environmental toxicological studies, but there are limited studies on its potential dietary molecular toxicity and physiology. The present study was the first to use multi-omics-based approaches to explore the fish intestine-liver axis under dietary Zn exposure. Golden pompano Trachinotus ovatus were exposed to different dietary concentrations (78.4, 134.6, and 161.4 mg/kg as the control, low-dose Zn, and high-dose Zn groups, respectively) of Zn for 4-week. Low-dose Zn exposure significantly promoted the fish growth, whereas the high-dose Zn exposure reduced the fish growth. Co-analysis of 16S diversity, metagenome and transcriptome showed that the low-dose Zn enriched the intestinal microflora and changed the dominant microflora abundances (Proteobacteria, Fusobacteria, Firmicutes and Bacteroidetes), as well as activated the growth hormone metabolism in the liver. Meanwhile, the high-dose of Zn caused the intestinal microbiota dysbiosis, activated the Type VI secretion systems (T6SSs), and further triggered the oxidative stress response, immunity, and antiviral function of the liver. Multi-omics revealed the interference of long-term Zn dietary exposure on the intestine-liver axis. There was an apparent homeostasis of Zn accumulation in the fish tissues, but the window of dietary Zn nutritional requirements versus toxicity appeared to be narrow for the golden pompano. These results provided new insight into the adverse effects and regulatory mechanisms of dietary Zn requirements and toxicity in marine fish.