Rouyer, L. S. F. | bioRxiv Science

bioRxiv2026

Bile acid chemosensation in mammals supports species and gut microbiome evaluation

The rodent vomeronasal system, also known as the accessory olfactory system (AOS), detects excreted chemosignals that guide social, reproductive, and defensive behaviors. Excretions sensed by the AOS contain blends of organic chemicals that reflect the biological identity of the emitter, but it remains unclear how the AOS extracts useful information from these complex natural cues. Vomeronasal sensory neurons (VSNs) sense bile acids, a diverse class of molecules excreted by vertebrates in feces. Using mass spectrometry, we found that patterns of bile acid excretion - not unique molecules - provide sufficient information to decode the emitters species, diet, and gut microbiome status. Using population calcium imaging, we found that VSN populations demonstrate an inverse relationship between natural bile acid abundance and population response magnitude and support efficient information encoding through stimulus "whitening." VSNs showed maximum sensitivity to taurine-conjugated bile acids, a novel class of vomeronasal ligands found at low natural abundance levels, that have high theoretical discriminatory value. VSN tuning patterns aligned strongly with theoretical axes for discriminating reptilian predators from vegetarians, and between mice with different gut microbiome states. These results reveal that the AOS extracts biological state from bile acid emission patterns through enhanced sensitivity to rare, information-rich ligands.

neuroscience↗

bioRxiv2024

Mammalian chemosensory bile acid detection supports species and gut microbiome evaluation

Long abstractThe rodent accessory olfactory system (AOS) detects environmental chemosignals and guides social and survival-oriented behaviors. Fecal bile acids activate neurons in the AOS, potentially serving as mammalian pheromones and kairomones, but few molecules in this large class have been evaluated thus far. We used live volumetric Ca2+ imaging to screen naturally occurring bile acids for their capacity to activate peripheral vomeronasal sensory neurons (VSNs). We found that taurine-conjugated bile acids (tauro-BAs), including taurine-conjugates of cholic acid, deoxycholic acid, lithocholic acid, and chenodeoxycholic acid (TCA, TDCA, TLCA, TCDCA, respectively) activate large populations of VSNs at sub-micromolar concentrations. Tauro-BA-sensitive VSNs rarely responded to unconjugated (CA, CDCA, DCA, LCA), glycine-conjugated (GCA, GDCA, GLCA, GCDCA), or keto-conjugated (7-keto DCA, 12-keto DCA, 7-keto LCA) bile acids. Tauro-BA-sensitive VSNs were also insensitive to well-studied sulfated steroids, suggesting tauro-BAs activate vomeronasal receptors that have not yet been de-orphaned. Among the tauro-BAs, TDCA displayed particularly strong potency, activating many VSNs at sub-micromolar concentrations. Tauro-BAs were not detectable in mouse fecal extracts by mass spectrometry, but were found in reptile fecal extracts and germ-free mouse fecal extracts. VSN responses to germ-free and conventional mouse fecal extracts, conjugated bile acids, and tauro-BAs revealed that non-overlapping populations of VSNs respond to germ-free and conventional mouse feces. A subset of VSNs that were activated by germ-free mouse fecal extracts responded to tauro-BAs, whereas VSNs responsive to conventionally fecal extracts responded to unconjugated bile acids. In vivo exposure to TDCA alone, and to mouse fecal extracts spiked with TDCA, elicited mild aversion and stress-associated behaviors in a non-social context (avoidance, digging, grooming, etc.). These studies establish tauro-BAs as a novel class of aversive vomeronasal ligands that vary in feces across species and gut microbiomes. Short abstractThe rodent accessory olfactory system (AOS) detects environmental chemosignals and guides social and survival-oriented behaviors. Fecal bile acids activate neurons in the AOS, but the full repertoire of bile acids that activate VSNs is not known. A live Ca2+ imaging screen revealed that VSNs were highly activated by taurine-conjugated bile acids (tauro-BAs) at sub-micromolar concentrations. Tauro-BAs were undetectable in conventionally raised mouse fecal extracts, but were found in reptile fecal extracts and germ-free mouse fecal extracts. VSN activity to tauro-BAs overlapped that of germ-free mouse fecal extracts, suggesting a link between bile acid chemosensation and the gut microbiome. When mice were exposed to taurodeoxycholic acid in vivo, they displayed mild aversion and stress-associated behaviors.

neuroscience↗