Systemic rhythmicity of host and bacterial bile acid amidates in the mouse

Bacterial bile acid amidates (BBAAs) represent an emerging class of host-microbe co-metabolites formed when gut bacteria conjugate bile acids with amino acids beyond taurine and glycine. Although these conjugates have been shown to modulate immune signaling and epithelial integrity, their spatial and temporal distribution across host tissues remains poorly understood. Here, we profiled 690 samples from time-restricted-fed mice, spanning 14 organs, digestive tract contents, and biofluids, to map the temporal dynamics of BBAAs. We identified widespread and tissue-specific oscillations of BBAAs, with the greatest temporal synchronization observed in the ileal contents and progressively diminished rhythmicity in the periphery. Amidates with hydrophilic or hydrophobic side chains remained relatively constant, while aromatic conjugates exhibited the most substantial variation. These findings reveal that BBAAs are temporally and spatially distributed throughout the body, supporting a model in which microbes encode systemic signals through the timing and structure of their metabolites.