Microbial Metabolites of Flavanols in Urine are Associated with Enhanced Anti-Proliferative Activity in Bladder Cancer Cells In Vitro

The Effects and Mechanisms of Flavonoids on Cancer Prevention and Therapy: Focus on Gut Microbiota

“…Lower the levels of colonic inflammatory proteins (COX-2 and iNOS) and fecal short-and branched-chain fatty acids [172] Block colonic carcinogenesis Reduce the fecal concentration of deoxycholic acid and hyodeoxycholic acid [174] Prevent colonic carcinogenesis Increase fecal concentration of bile acids and cholesterol; decrease the level of colonic and intestinal cholesterol and raise tissue phospholipid content [177] Suppress the growth of Enrich the population of Bacteroidetes and decrease the [ Produce bioactive metabolites (e.g., urolithins) by gut microbiota [193] Pomegranate Inhibit the proliferation of prostate cancer cells Produce the bioactive metabolite, urolithin A, by gut microbiota [197] Daidzein/equol Soybean Increase the chemosensitivity of breast cancer cells Suppress the activity of the drug transporter, breast cancer resistance protein [194] S-equol Soybean Suppress the proliferation and promote the apoptosis of breast cancer cells Upregulate miR-10a-5p and block the PI3K/AKT signaling pathway [195] Flavanol Grape Inhibit the proliferation of bladder cancer cells Produce bioactive metabolites (hippuric acids, phenylalkyl acids and valerolactones) by gut microbiota [11] Catechin Green tea Inhibit colonic carcinogenesis Decrease the fecal concentration of lithocholic acid and hyodeoxycholic acid [174] Inhibit the proliferation of prostate cancer cells Produce the bioactive metabolite, 5-(3', 4', 5'-trihydroxyphenyl)-γ-valerolactone, by gut microbiota [197] Epigallocatechin/ Epigallocatechin gallate Green tea Inhibit the proliferation of cervical cancer cells Produce bioactive metabolites (EGC-M2, EGC-M7 and EGC-M9) by gut microbiota [198] Epicatechin Green tea Inhibit the proliferation of cervical cancer cells Produce the bioactive metabolite, EC-M9, by gut microbiota [198] Icariside I Epimedium Restrain melanoma growth Elevate the abundance of Bifidobacterium spp. and Lactobacillus spp.…”

“…Gut microbiota converted flavanols into bioactive metabolites that were mainly excreted via urine 11 . Uroepithelial cells are thus exposed to high concentrations of flavonoid metabolites.…”

“…Recently, flavonoids are found to be involved in cancer biology by reshaping gut microbiota 10 . Bioactive metabolites produced by gut microbiota from flavonoids exert an inhibitory effect on carcinogenesis 11 .…”

Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health

“…High-molecular weight oligomers and polymers are poorly absorbed, however once metabolized by the gut microbiome their metabolites can be absorbed, deposited into circulation, and ultimately excreted in urine [ 19 , 20 ]. Flavanol feeding interventions in antibiotic (Abx) treated animals support this integral role of the gut microbiome in producing bioavailable and beneficial metabolites [ 1 , 21 , 22 ]. Evidence shows that bioavailable flavanol microbial metabolites may possess greater bioactivity than the native flavonoids [ 8 , 19 , 21 , 23 ].…”

“…Most in vitro microbial metabolite studies rely on commercially available purified metabolites which do not adequately recapitulate the complex physiological mixtures of compounds generated by the gut microbiome in vivo. We previously investigated the profiles of bioavailable native and metabolite compounds in rats treated with or without Abx and supplemented with high molecular weight flavanol rich grape seed extract (GSE), low molecular weight flavanol monomers catechin and epicatechin (C/EC), or a control [ 22 ]. Urinary flavanol metabolites (valerolactones, phenylalkyl acids, and hippuric acids) were associated with reduced cancer cell proliferation in vitro [ 22 ].…”