Ace2 mutation disrupts amino acid absorption, impairs growth, and alters microbiota dynamics in zebrafish

Angiotensin-converting enzyme 2 (Ace2) is a well-studied enzyme with important physiological functions in mammals. However, its roles in non-mammalian animals remain largely unexplored. This study investigates the function of Ace2 in zebrafish using CRISPR/Cas9-generated ace2 mutants (-/-). The ace2^-/- mutants exhibited significant growth retardation with reduced body length and weight. High ace2 expression was found in the intestine, indicating its importance in gut function. Ace2 deficiency led to marked decreases in specific plasma and muscle amino acids, including cationic and neutral amino acids such as L-(+)-arginine, L-(+)-lysine, leucine, and valine, suggesting impaired amino acid absorption. The gut microbiota of ace2^-/- mutants showed reduced diversity and altered bacterial communities, with marked increases in expression of genes involved in bacterial carbohydrate metabolism and marked decreases in amino acid biosynthesis pathways. These findings are consistent with enhanced carbohydrate metabolism in the liver and reduced amino acids in muscle. Our study demonstrates the essential role of Ace2 in growth, amino acid metabolism, and gut microbiota balance in zebrafish, offering novel insights into its functions across vertebrate species.