• Berberine (BBR) disrupts male reproductive function by reducing serum testosterone, sperm concentration, mating rate, and fecundity in mice.
• The gut microbiota, specifically Muribaculaceae, is essential for spermatogenesis; BBR-induced reduction in Muribaculaceae abundance is a primary cause of impaired spermatogenesis.
• Muribaculaceae regulates ornithine metabolism, which in turn modulates LDLR-mediated testosterone synthesis in Leydig cells.
• Fecal microbiota transplantation or Muribaculaceae supplementation may offer a therapeutic strategy for infertility associated with gut microbiota dysbiosis.
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