Species-specific deglucuronidation of quercetin glucuronides by the human gut microbiota

The gut microbiota plays a pivotal role in human health and interacts with quercetin, which undergoes extensive glucuronidation in the host organism. Microbial β-glucuronidases can deconjugate quercetin monoglucuronides, regenerating the aglycone and modulating bioavailability; however, the magnitude and drivers of inter-individual variability remain unclear. We assembled a panel of human-derived intestinal isolates and quantified the deglucuronidation of four regioisomeric quercetin monoglucuronides using intact whole cells. Deglucuronidation capacity varied by approximately an order of magnitude across taxa and depended on the conjugation site: A/C-ring glucuronides were generally more labile than B-ring forms, with some species-specific exceptions. Notably, Faecalibacterium duncaniae emerged as a high-efficiency, broad-coverage deglucuronidator, outperforming the other isolates across all substrates. Whole-community assays of cecal content and fecal pellets echoed these preferences and revealed higher activity in digesta. These findings delineate species-resolved deglucuronidation patterns underlying inter-individual differences in quercetin bioavailability and identify species microbiota-driven deconjugation into pharmacokinetic models.