Identification of Novel Metabolic Signatures on Human Gut Microbiota: Ellagic Acid, Naringenin, and Phloroglucinol

Phenolic compounds are widely known for their beneficial effects on human health. However, it is essential to understand which low molecular weight metabolites are produced by the gut microbiota, when non-absorbed compounds reach the colon, and whether these metabolites are more biologically active than their precursors. In this context, this study aims to explore the gut microbiota metabolites of relevant phenolic compounds commonly found in the human diet. Therefore, ellagic acid, naringenin, and phloroglucinol were incubated with human feces for 48 h, and the ensuing metabolites were analyzed by ultra-high-performance liquid chromatography with diode array detector coupled to ion trap mass spectrometry (UHPLC-DAD-MSⁿ) and gas chromatography-mass spectrometry (GC-MS). Ellagic acid metabolism by the gut microbiota produced a diversity of urolithins, with 8-hydroxyurolithin being identified for the first time. Isomers of 4-hydroxybenzoic, 3,4-dihydroxybenozic, and p-coumaric acids were identified for the first time as naringenin metabolites, while phloroglucinic, 2-hydroxy-3-phenylpropanoic, 3-phenylpropanoic, and 2-phenylacetic acids are reported for the first time as phloroglucinol metabolites. These findings contribute to a more comprehensive understanding of the beneficial health effects of these metabolites through the evaluation of their biological activities in conjunction with their effects on the gut microbiota, thus providing the basis for the development of food supplements, novel probiotics or functional foods.