Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut

Summary Abnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer. Recent studies suggested that gut bacteria can alter sex steroid profile of host; however, the underlying mechanisms and bacterial taxa remain elusive. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of aerobic and anaerobic androgen catabolism in environmental conditions (37°C) resembling the mammalian gut. The strain GDN1 administration to C57BL/6J mice through oral gavage profoundly affected gut bacterial community, along with an approximately 50% reduction in serum androgen level in male mice. Our RT–qPCR results revealed the differential expression of aerobic and anaerobic androgen catabolic genes in the mouse ileum (microaerobic) and caecum (anaerobic), respectively. Furthermore, androgenic ring-cleaved metabolites were detected in the mouse fecal extract. This study discovered that androgen serves as a carbon source of gut microbes and that androgen-catabolizing gut bacteria can modulate host circulating androgen levels. Highlights Thauera sp. strain GDN1 administration through oral gavage regulated mouse serum androgen levels. The biochemical, genetic, and metabolite profile analyses revealed the occurrence of bacterial androgen catabolism in the mouse gut. Androgen catabolism proceeds through the O 2 -dependent and O 2 -independent catabolic pathways in mouse ileum and caecum, respectively. A possibility to harness Thauera sp. strain GDN1 as a functional probiotic to treat hyperandrogenism. Graphical Abstract In brief Hsiao et al. found that oral administration of androgen-catabolizing Thauera species regulated mouse serum androgen level. They characterized the gut microbe–mediated androgen catabolism through genetic and biochemical analyses. Their discovery portends a possibility of harnessing androgen-catabolic gut bacteria as functional probiotics to treat hyperandrogenism.