Curcumin alleviates zearalenone-induced reproductive impairment by modulating the gut microbe–testis axis

Zearalenone (ZEN), a mycotoxin commonly found in cereal crops and foods, induces testicular damage and disrupts gut microbial composition, revealing a critical connection between gut microbes and the male reproductive system. Curcumin (CUR), a bioactive compound derived from ginger, is known to enhance intestinal microecological balance and exhibit anti-inflammatory properties. This study aimed to investigate the mechanism by which CUR alleviates ZEN-induced reductions in sperm quality through modulation of the gut microbe–testis axis. Forty-eight 6-week-old Balb/c male mice were randomly assigned to four treatment groups: control (CON), CUR (200 mg/kg body weight CUR), ZEN (40 mg/kg body weight ZEN), and ZEN + CUR (200 mg/kg CUR + 40 mg/kg ZEN). The experiment lasted 28 days. CUR was found to mitigate ZEN-induced reductions in testosterone levels, testicular structural damage, and disrupted spermatogenesis. ZEN exposure altered gut microbial composition, increasing the abundance of Prevotella while decreasing that of Lactobacillus. CUR counteracted these effects and reduced the ZEN-induced activation of IL-17A-TNF-α signaling pathway proteins. In conclusion, ZEN induces testicular inflammation and reduced sperm quality by lowering testosterone levels and disrupting gut microbial balance, which drives the testicular IL-17A signaling pathway. CUR alleviates ZEN-induced testicular inflammation and sperm quality reduction by restoring beneficial gut microbes and testosterone levels.