Presentation Details
| Development- and Microbiome-driven Bile Acid Signatures as Social Chemosignals in the Mouse Vomeronasal System VarunHaran Manoharan, Julian P Meeks. University of Rochester Medical School, Rochester, NY, USA |
Abstract
Early postnatal development is characterized by rapid maturation of the gut microbiome, which reshapes the host metabolic landscape and alters the excretion of bile acids (BAs). Fecal BAs are known to activate the accessory olfactory system (AOS), but the mechanisms by which these internal microbial and physiological cues are transduced into external social chemosignals remain elusive. We performed mass spectrometric analysis of fecal samples from neonatal, conventional adult (CF), and germ-free (GF) mice. Taurine-conjugated BAs were significantly enriched in GF and neonatal samples compared to CF. UMAP dimensionality reduction and density-based cluster analysis showed that neonatal profiles were positioned closer to GF mice than to CF, suggesting that the neonatal metabolic landscape reflects an immature microbial state. Vomeronasal sensory neurons (VSNs) were then exposed to a panel of fecal extracts (neonate, juvenile, adult, and GF) and synthetic BAs, including cholic acid (CA), taurocholic acid (Tauro-CA), and tauro-β-muricholic acid (Tauro-β-MCA), and live volumetric Ca2+ imaging was performed using OCPI microscopy. Distinct VSN populations selective for neonate, juvenile and adult fecal samples were identified, demonstrating the AOS’s ability to discriminate developmental stages. Specifically, the CA-responsive cluster overlapped neonate, juvenile, and adult responses, but not GF. Tauro-CA-responsive VSNs overlapped neonate, juvenile, and GF signatures, with minimal adult overlap. Similarly, Tauro-β-MCA-responsive neurons aligned with juvenile and GF, but showed little overlap with neonate or adult samples. These findings suggest that the AOS deciphers developmental and microbiome status via specific BA chemosignals, thereby linking internal physiological states to external communication.
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