Gut microbial metabolite phenylacetylglycine disrupts spermatogenesis in Ggt1-deficient mice via β2AR-STAT3-STAT5B pathway (microbiomejournal.biomedcentral.com)

• Ggt1 deletion causes gut dysbiosis and elevates microbial PAGly.
• PAGly acts on Leydig cell β2AR to disrupt spermatogenesis via STAT3/STAT5B.
• Fecal microbiota transplant transfers infertility to wild-type mice.

"This study reports that deletion of the gamma-glutamyl transferase 1 (Ggt1) gene in mice leads to gut microbiota dysbiosis and elevated levels of the microbial-derived metabolite phenylacetylglycine (PAGly) in serum and testes. PAGly activates the β2-adrenergic receptor on Leydig cells, triggering STAT3 phosphorylation, SOCS3 upregulation, and suppression of STAT5B-mediated Klk1b transcription, impairing spermatogenesis. Blocking PAGly restores fertility, and fecal microbiota transplantation recapitulates the phenotype. The data are deposited in public repositories."