Microbial reactivation of host androgens directs enteric neuronal regulation of gut motility - PubMed
4 hours ago
- #gut motility
- #androgen signaling
- #microbiome
- Androgen signaling to Nos1+ enteric neurons and Scn10a+ spinal afferent neurons is essential for normal intestinal transit in mice, and this process is dependent on the microbiome.
- Antibiotic-induced microbial depletion abolished androgen receptor expression in enteric neurons, reduced serum testosterone, and led to gut dysmotility, indicating that androgens are necessary for antibiotics to affect transit and can partly rescue dysmotility.
- Nos1 neurons upregulate androgen receptor during puberty, coinciding with changes in fecal bacterial beta-glucuronidase (GUS) enzymes, which can deconjugate steroid glucuronides in both mice and humans.
- Intracolonic administration of a specific GUS enzyme that metabolizes androgen glucuronides restored neuronal androgen signaling in microbiome-depleted mice, showing that gut microbes reactivate host-excreted androgens via GUS enzymes.
- This microbial reactivation of androgens represents a crucial dynamic interaction between gut microbiota and the host that is vital for peripheral nervous system function in maintaining gut motility homeostasis.