Metabolic Fate of Dietary Glucosinolates and Their Metabolites: A Role for the Microbiome

Abstract

Robust evidence shows that phytochemicals from cruciferous vegetables, like broccoli, are associated with numerous health benefits. The anti-cancer properties of these foods are attributed to bioactive isothiocyanates (ITCs) and indoles, phytochemicals generated from biological precursor compounds called glucosinolates. ITCs, and particularly sulforaphane (SFN), are of intense interest as they block the initiation, and suppress the progression of cancer, through genetic and epigenetic mechanisms. The efficacy of these compounds is well-demonstrated in cell culture and animal models, however, high levels of inter-individual variation in absorption and excretion of ITCs is a significant barrier to the use of dietary glucosinolates to prevent and treat disease. The source of inter-individual ITC variation has yet to be fully elucidated and the gut microbiome may play a key role. This review highlights evidence that the gut microbiome influences the metabolic fate and activity of ITCs. Human feeding trials have shown inter-individual variations in gut microbiome composition coincides with variations in ITC absorption and excretion, and some bacteria produce ITCs from glucosinolates. Additionally, consumption of cruciferous vegetables can alter the composition of the gut microbiome and shift the physiochemical environment of the gut lumen, influencing the production of phytochemicals. Microbiome and diet induced changes to ITC metabolism may lead to the decrease of cancer fighting phytochemicals such as SFN and increase the production of biologically inert ones like SFN-nitrile. We conclude by offering perspective on the use of novel "omics" technologies to elucidate the interplay of the gut microbiome and ITC formation.

Keywords: bacteria; broccoli sprouts; cruciferous vegetables; glucosinolate; isothiocyanate; microbiome; sulforaphane; sulforaphane nitrile.

Figure 1

During chewing of raw broccoli sprouts, plant myrosinase converts glucoraphanin (GRP) to sulforaphane (SFN) in the mouth. In the gut lumen, GRP is further converted to either SFN or sulforaphane-nitrile (SFN-NIT) by the gut microbiome. It is unclear if microbes conjugate SFN to glutathione (GSH), however, only free SFN is taken up into enterocytes. Within the enterocyte, SFN-GSH is either excreted back into the gut lumen or enters circulation where it is exists as SFN-GSH or in its free form which conjugates with blood proteins. SFN is transported to either tissues where it exerts its bioactivity or to the liver where it is metabolized via the mercapturic acid pathway. Mercapturic acid metabolites, SFN-cysteine (SFN-Cys) and SFN-N-Acetyl-Cysteine (SFN-NAC), from the liver are either exported to the bile for excretion to the feces, or back into the blood to go to tissues. SFN also goes to the kidney where it is converted to SFN-NAC and excreted into the urine. Un-hydrolyzed GRP is either excreted into the feces or absorbed where it is either transported to the kidneys to be excreted in urine or to the liver where it is excreted into bile. GRP that undergoes enterohepatic circulation and is either hydrolyzed in the gut or excreted to the feces. SFN-NIT is absorbed from the gut lumen where it is transported to kidneys for excretion into urine. SFN-NIT metabolism in humans needs further investigation.