The Role of the Gut Microbiome in Quercetin Inhibition of Sulforaphane Bioavailability and Bioactivity in Rats

Abstract

Broccoli is a rich source of both glucoraphanin (GRP) and quercetin glycoside, precursors of the health promoting food components, sulforaphane (SFN) and quercetin, respectively. Considering that the content of quercetin in broccoli is reported to vary up to 400‐fold, the aim of this study was to investigate the impact of quercetin levels on SFN bioavailability and bioactivity. Four different doses of quercetin (0.3, 2, 10 and 50 mg/kg BW), chosen to model broccoli content of quercetin, together with a single dose of GRP (30 mg/kg BW) were gavaged in twenty‐four adult male F344 rats daily for five days. SFN recovery in the urine and colonic NAD(P)H: quinone oxidoreductase 1 (NQO1) activity were measured for SFN bioavailability and bioactivity, respectively. Surprisingly, in contrast to reported synergy among quercetin and sulforaphane, a moderate negative correlation between quercetin level and colonic NQO1 activity (r= −0.40, p=0.37, one‐tailed non‐parametric Spearman's rank test) was found. Furthermore, we observed a strong negative correlation between quercetin level and SFN recovery in the urine (r= −1.00, p=0.04), suggesting that in rats, quercetin may inhibit SFN bioavailability, leading to inhibition of bioactivity. To investigate the underlying mechanism of inhibition by quercetin, we examined GRP hydrolysis by cecal microbiota ex vivo. Remarkably, consistent with the above findings, a strong negative correlation was observed between quercetin content and GRP hydrolyzing activity of cecal microbiota (r= −1.00, p=0.04), indicating that the inhibition of SFN bioavailability and bioactivity by quercetin might be through decreased GRP hydrolyzing activity in cecal microbiota. When quercetin and GRP were incubated with microbiota from un‐exposed rats, there was no direct inhibitory effect on GRP hydrolysis during a two‐hour incubation (p=0.458), suggesting that inhibition requires chronic exposure to quercetin. In conclusion, our study suggests that quercetin‐rich broccoli may interfere with SFN bioavailability and bioactivity, through decreasing the GRP hydrolyzing activity of cecal microbiota.Support or Funding InformationUSDA/NIFA 2016‐67017‐24430