In vitro gut microbial catabolism of ferulic acid is characterized by interindividual variability.

Interindividual variability in gut microbial metabolism of 4'-hydroxy-3'-methoxycinnamic acid (ferulic acid, FA), a major phenolic acid in cereals, may influence health outcomes and nutritional guidance; however, distinct metabotypes remain poorly defined. We investigated FA metabolism using in vitro fecal batch incubations from 18 individuals, combining ¹H NMR metabolomics with 16S rRNA amplicon sequencing. All individuals produced a shared set of FA-derived catabolites, but differed markedly in the rate and extent of FA conversion, enabling the identification of interindividual metabolic signatures. FA degradation was slower in older donors. Early 3-(3'-hydroxyphenyl)propanoic acid producers had lower tryptophan, and high 3-phenylpropanoic acid producers exhibited higher fumarate compared to higher 3-(3',4'-dihydroxyphenyl)propanoic acid producers. Late 3'-hydroxyphenylacetic acid producers had higher alpha diversity. Microbiota composition showed only weak associations with metabolic signatures, suggesting that functional variability rather than taxonomic differences drives interindividual differences in FA catabolism. These findings support the existence of functional FA metabolic signatures and highlight the need for in vivo studies to elucidate their physiological relevance.