Prioritization and Bioactivity Characterization of Novel Bile Acids Produced by the Microbiome

This project, titled "Prioritization and Bioactivity Characterization of Novel Bile Acids Produced by the Microbiome," addresses an emerging frontier at the intersection of microbiology, metabolism, and chemical biology. Bile acids are increasingly recognized not only as detergents for lipid digestion but also as signaling molecules that influence host physiology, immune function, and metabolic homeostasis. The human microbiome contributes to the chemical diversity of bile acids by transforming primary host-derived bile acids into structurally modified, microbially derived variants. Many of these novel bile acids remain uncharacterized, and their relative abundance, biological activities, and relevance to human health and disease are poorly understood. The project aims to systematically identify, prioritize, and characterize these microbiome-produced bile acids to determine which molecules merit deeper investigation for mechanistic studies and potential translational application.

Central goals include assembling a catalog of novel bile acid structures detected in microbiome samples, applying criteria to prioritize candidates based on prevalence, novelty, and potential bioactivity, and conducting targeted bioactivity characterization to define effects on relevant host pathways. By prioritizing molecules rather than attempting exhaustive characterization of every detected variant, the project seeks to focus resources on compounds most likely to influence host biology. The characterization phase will probe bioactivity across relevant cellular systems and biological readouts to establish whether prioritized bile acids act as signaling ligands, modulators of metabolic enzymes, or effectors of immune responses. A key outcome will be a ranked portfolio of microbially produced bile acids annotated with preliminary bioactivity profiles, contextual information about occurrence in human or model microbiomes, and recommendations for follow-up mechanistic or translational studies. Such a resource can guide downstream hypothesis-driven research, inform biomarker discovery, and support exploration of therapeutic avenues that harness or modulate microbiome-derived metabolites. The anticipated impact spans basic science, by illuminating microbe-host chemical communication, and potential clinical relevance, since bile acid signaling perturbations have been implicated in metabolic disorders, inflammatory diseases, and other conditions.

The project emphasizes rigorous prioritization to ensure that subsequent efforts are both efficient and strategically focused, enabling the research community to move from descriptive catalogs toward functional understanding. By delivering a curated set of prioritized novel bile acids with initial bioactivity characterization, the project will lower barriers for investigators seeking to study these metabolites, encourage cross-disciplinary collaborations among microbiologists, chemists, and clinicians, and create a foundation for future mechanistic and translational investigations into how the microbiome shapes host physiology through specialized metabolites.