Gut microbe–derived <i>N</i> -acyl serinol lipids shape host postprandial metabolic homeostasis

Although strong evidence links the gut microbiome to metabolic disease, the mechanisms linking microbiota to hormonal and metabolic responses to food are not well understood. After a meal, gut bacteria produce a wide array of small molecule, protein, and lipid metabolites originating from bacterial sources. Attributing physiological function to select gut microbe-derived metabolites is critical to understanding diet-microbe-host interactions, and to developing microbiome-inspired therapies to improve human health. Here, we have investigated the role of a poorly annotated class of gut microbiome-derived lipids called <i>N</i>-acyl amides in postprandial metabolic physiology. Here, we show that both bacterial production and provision of exogenous <i>N</i>-acyl amides reorganize host hormone-driven metabolic transition after a meal. Moreover, <i>N</i>-acyl amides exert broad effects on the meal- and circadian-related reorganization of gene expression, metabolic hormones, and gut microbiome composition. Collectively, these results demonstrate that microbiota-derived <i>N</i>-acyl amides play a physiologic role in postprandial metabolic homeostasis in the host.