Multi-omics analyses reveal gut microbiota-driven biotransformation of sorghum (poly)phenols in pigs

Sorghum is rich in (poly)phenols and condensed tannins with diverse biological activities, but their gastrointestinal metabolism and the fate of microbiota-associated metabolites in muscle remain poorly understood. This study investigated the metabolic fate of sorghum (poly)phenols in pigs using UPLC-Orbitrap-MS, multi-omics analyses (metagenomics, metatranscriptomics, and metabolomics), and in vitro validation. Sorghum contained higher levels of (poly)phenols than corn, with high-tannin sorghum showing the greatest abundance. Sorghum feeding increased flavonoids and phenolic acids throughout the gastrointestinal tract. During digestion, condensed tannins remained relatively stable, whereas flavonoid glycosides were deglycosylated to aglycones. In the colon, further flavonoid conversion to phenolic acids was associated with microbial activity. Metagenomic and metatranscriptomic analyses implicated candidate genes associated with flavonoid transformation, with fcr and phy showing significantly higher transcript abundances in HTS than in CON and LTS. In vitro, tested Flavonifractor plautii and Eubacterium ramulus strains transformed selected flavonoids into phenolic acids with distinct substrate preferences under the conditions examined. Moreover, microbiota-associated metabolites, including hippuric acid, were detected in longissimus dorsi muscle. These findings characterize the spatiotemporal metabolic fate of sorghum (poly)phenols and support a role for gut microbiota in shaping their bioavailability and metabolic fate.