Pyroglutamyl peptide–rich rice protein hydrolysate restores cecal N -acetyl amino acids in high-fat-diet–fed rats, outperforming short-chain fatty acids as early microbial markers

Abstract Pyroglutamyl-leucine (pyroGlu-Leu) is a food-derived modified peptide known to modulate the gut microbiota. This study examined the effects of orally administered rice protein hydrolysate (RPH) containing pyroGlu-Leu in rats fed a 45% high-fat diet that induced mild dysbiosis without obesity or severe liver dysfunction. In addition to short-chain fatty acids (SCFAs), several N-acetyl amino acids (NAAAs) were detected in cecal contents. The high-fat diet significantly decreased both SCFAs and NAAAs, whereas administration of RPH or synthetic pyroGlu-Leu restored the levels of NAAAs despite not recovering those of SCFAs. RPH did not alter the overall gut microbial composition but modified specific bacterial taxa that correlated with NAAA levels. These results suggest that NAAAs are gut microbiota-derived metabolites that respond more sensitively to food-derived modulation of the gut microbiota than SCFAs, and may serve as early indicators of microbiota–host metabolic interactions.