Bile acid chemosensation in mammals supports species and gut microbiome evaluation

Abstract The rodent accessory olfactory system (AOS) detects chemosignals emitted by conspecifics and other species to support beneficial behaviors. Peripheral vomeronasal sensory neurons (VSNs), the AOS’ chemical sensors, detect fecal bile acids in patterns that have unknown significance to the animal. We used a combination of mass spectrometry and VSN calcium imaging to investigate the AOS’ capacity to use bile acid information to discriminate between fecal samples from captive reptiles and mice with varying gut microbiome states. Mass spectrometry analysis revealed bile acid patterns that distinguished biologically relevant samples from one another, representing theoretical discrimination axes. We measured VSN response patterns to bile acid stimuli aligned with theoretical discrimination axes. We found that VSNs perform stimulus “whitening” via an inverse relationship between natural bile acid abundance and population response magnitude. VSNs showed maximum sensitivity to taurine-conjugated bile acids, which have high theoretical discriminatory value, but were found at low natural abundance levels. Individual taurine-conjugated bile acids drove threat assessment behavior when added to familiar mouse fecal extracts, suggesting high behavioral significance. Finally, we analyzed the degree to which the AOS utilizes the theoretical information about species, diet, and gut microbiome status from bile acids. We found that VSN tuning patterns align with theoretical axes for discriminating reptilian predators from vegetarians, and between mice with different gut microbiome states. VSN tuning was especially well-aligned with the information available about conspecific gut microbiome status. These results show that AOS bile acid chemosensation supports discrimination of multiple biologically relevant states. Short abstract The rodent accessory olfactory system (AOS) detects fecal bile acids via combinatorial codes with unknown biological significance. We investigated whether AOS bile acid chemosensation supports species and gut microbiome evaluation using mass spectrometry, calcium imaging in vomeronasal sensory neurons (VSNs), and analytical modeling. Bile acid excretion patterns theoretically supported discrimination of reptilian predators from vegetarians, and germ-free mice from conventionally raised counterparts. VSNs demonstrated stimulus “whitening” via an inverse relationship between natural bile acid abundance and population response magnitude. VSNs had highest sensitivity to taurine-conjugated bile acids, a novel class of chemosignals that elicited behavioral aversion. VSN tuning aligned with ideal discrimination axes, which was especially strong for gut microbiome-associated bile acid abundance patterns. These results show that AOS bile acid chemosensation supports discrimination of multiple biologically relevant states. Competing Interest Statement The authors have declared no competing interest. Footnotes Funding Sources: This work was principally supported by the National Institute on Deafness and Other Communication Disorders, part of the United States National Institutes of Health, via grant R01DC017985 (JPM). Partial support came grants R56DC015784 (JPM) and R01DC021213 (JPM). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.