A comprehensive study from UC San Diego catalogs 851 distinct N-acyl lipids across human tissues and biofluids, including 777 previously unidentified compounds. The findings illuminate crucial metabolic pathways regulating immune and stress responses, with significant variation influenced by diet and microbiome composition. This expanded metabolic lexicon enhances understanding of human physiology and disease, especially conditions linked with microbiome alterations, providing a foundation for novel diagnostic and therapeutic avenues.