Quercetin microgels alter gut metabolome and reverse oxidative damage in vitro

Colonic delivery of quercetin using encapsulation techniques is an effective approach in maximizing quercetin efficacy against oxidative-stress related diseases such as inflammatory bowel disease. We hypothesized that colon-targeted delivery of quercetin with quercetin loaded alginate-chitosan microgels (ALQ) could alter colonic microbial metabolism regulating microbial metabolites production that may exert biological effects at the cellular level. To demonstrate this, ALQ were subjected to colonic fermentation using human fecal microbiota with empty microgels (AL) as control, and fermented fecal samples were collected at 0, 8, and 24 h. Short chain fatty acid analysis using gas chromatography showed that ALQ increased productions of acetic acid, while decreased isobutyric and isovaleric acid production. Semi-targeted metabolome scanning using Orbitrap mass spectrometer showed that the overall metabolome profile was remarkably different between AL and ALQ treatments at both 8 h and 24 h of fermentation. There were 9 metabolites at 8 h, and 54 metabolites at 24 h that were significantly regulated with more than 2-fold changes between AL and ALQ treatments. The metabolites included quercetin derived metabolites, amino acids and their derivatives, nucleotide derivatives, and organic acids. ALQ significantly modulated tyrosine metabolism, amino acids metabolic pathways, and the tricarboxylic acid cycle. These ALQ modulated metabolites in turn protected the Caco-2 cells from lipopolysaccharides induced injury, increased cellular antioxidant activities, and alleviated lipid oxidation induced by H 2 O 2 . Conclusively, ALQ could alter human fecal metabolome in vitro with significant shifts in key metabolites and exert antioxidant effects on cellular level, exhibiting potentials in colonic disease management.