Sea Cucumber Peptides Promote Testosterone Synthesis in Male Mice: Possibly via <i>Alistipes</i> ‐Bile Acid‐FXR Signaling Pathway

In this study, the effects of sea cucumber peptides (SCP) on hormonal regulation in male mice and their underlying mechanisms were explored. SCP was administered to mice, followed by in vivo mating experiments, serum hormone profiling, gene expression analysis, and intestinal microbiome characterization. The impact of SCP on key intestinal bacteria was further validated using in vitro antibacterial assays. In vivo, SCP effectively improved mating ability, increased serum levels of testosterone, and enhanced the expression of testosterone synthesis-related genes. Furthermore, these phenomena may be related to the significant inhibition of Alistipes in the colon of mice by SCP. In vitro, SCP demonstrated antimicrobial activities against Alistipes, characterized by disruption of its cellular membrane integrity and suppression of bile salt hydrolase (BSH) activity. Consistently, there was a significant increase in serum total conjugated bile acids, accompanied by reduced fecal BSH activity and downregulation of farnesoid X receptor (FXR) expression in the testis. Correlation analysis suggested that SCP may promote testosterone synthesis through the Alistipes-bile acid-FXR signaling pathway. Conclusively, SCP can promote testosterone synthesis in male mice through the gut-testosterone axis, providing a new perspective for the study of active peptide-regulated hormones.