The diversity and adjustability of metal-organic complex enhance the function of metals and promote the burgeoning fields of chemical biology. In the present study, we chose two marine fish to explore the effects of a dihydromyricetin (DMY)-Zn(II) complex on the intestinal microbiome composition and liver biological function using high-throughput sequencing technology. Two economic fish species commonly found in Southern China (golden pompano Trachinotus ovatus and pearl gentian grouper ♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatus) were exposed to dietary DMY-Zn complex for 4-week. Our study found that DMY-Zn performed a vital function on the improved anti-oxidative ability of both fish species. The Zn complex improved the stability of microbial community structure of the golden pompano by enhancing the α-diversity, but its impacts on the composition and diversity of intestine microorganisms of grouper were insignificant. BugBase results showed that the intestine microbiota following DMY-Zn exposure contained a lower abundance of potentially pathogenic bacteria and higher abundance of aerobic bacteria. Intestine health and utilization of carbohydrates were improved in the golden pompano, and unclassified bacteria were significantly enriched in the grouper. Liver transcriptome indicated that DMY-Zn affected the oxidative phosphorylation process (OXPHOS). Specifically, the OXPHOS process (map00190) was activated by promoting the glucose uptake (map04251, map04010) in golden pompano and lipid metabolism (map00071, map00140, map00062 and map00564) in grouper. Such difference in the responses of intestine microbiome and liver metabolism may be possibly explained by their different Zn basal requirements. Our study demonstrated that different fish species may have different responses to dietary DMY-Zn complex. The results provided a reference for the application of new additives in aquatic animal feed, and new insights into the roles of metal-organic complex in their biological impacts on fish.

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