@article{griffin_kohrt_rathore_kay_grabowska_neilson_2022, title={Microbial Metabolites of Flavanols in Urine are Associated with Enhanced Anti-Proliferative Activity in Bladder Cancer Cells In Vitro}, volume={74}, ISSN={["1532-7914"]}, url={https://doi.org/10.1080/01635581.2020.1869277}, DOI={10.1080/01635581.2020.1869277}, abstractNote={Dietary flavanols and their metabolites are excreted primarily via the urine, suggesting uroepithelial cells as a site of activity due to lengthy exposure to high concentrations of these compounds. Flavanols are metabolized by the gut microbiota to numerous bioavailable metabolites. The observed effects of flavanols, including cancer chemoprevention, may be due in part to the activities of microbial metabolites. Most in vitro mechanistic work in this area relies on a limited pool of commercially available or synthesized flavanol microbial metabolites, and little work has been done in the area of bladder cancer. The impact of physiologically relevant mixtures of native flavanols and their metabolites generated in vivo remains unknown. Rats were fed various flavanols after which 48 h urine samples, approximating the total bioavailable metabolome, were collected. Urine samples were profiled by UPLC-MS/MS, and their anti-proliferative activities were assayed in vitro in four bladder cancer cell models. Significant interindividual variability was observed for chemical profiles and anti-proliferative activities. Concentrations of microbial metabolites (valerolactones, phenylalkyl acids and hippuric acids) were positively associated with reduced bladder cancer cell proliferation in vitro, while native flavanols were poorly correlated with activity. These results suggest that microbial metabolites may be the primary compounds responsible for chemoprevention in uroepithelial cell following flavanol consumption. Furthermore, this highlights the potential for exploiting knowledge about individual genetics, microbiome profiles, flavonoid metabolism profiles, tumor characteristics, etc. to design personalized dietary interventions for cancer prevention and/or adjuvant therapy to reduce bladder cancer incidence and improve outcomes.}, number={1}, journal={NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL}, author={Griffin, Laura E. and Kohrt, Sarah E. and Rathore, Atul and Kay, Colin D. and Grabowska, Magdalena M. and Neilson, Andrew P.}, year={2022}, month={Jan}, pages={194–210} }
 @article{lloyd_griffin_krueger_beales_barlow_sheets_ekpo_ross_chandra_rathore_et al._2020, title={Supplemental treatment options for diabetes: how flavanol metabolites improve beta-cell function}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.05762}, abstractNote={Diabetes is one of the fastest growing non‐infectious diseases in the world. Current treatments are composed of pharmaceutical agents that enhance insulin sensitivity and eventual insulin monotherapy. Type 2 diabetes is characterized by insulin insensitivity of peripheral tissue, glucose intolerance, and β‐cell dysfunction. Dietary interventions may benefit patients with diabetes, and various plant derived flavonoids have been shown to exert anti‐diabetic effects. While these flavonoids are large, difficult to absorb, and rarely found in circulation, gut bacteria metabolize these into smaller metabolites which can be observed in circulation. We hypothesize that these gut bacteria derived flavanoid metabolites are absorbed and have direct effects on β‐cell function. Male outbred wistar rats were fed one of three diets in the presence or absence of antibiotic treatment: standard diet, standard diet supplemented with catechin hydrate and epicatechin, or standard diet supplemented with grape seed extract. Total urine was collected from the animals (representing the total amount of absorbed metabolites), then metabolites were extracted and reconstituted in water. Here we present data regarding the in vitro effects of these absorbed gut bacteria derived flavanoids on INS‐1 832/13 β‐cell insulin secretion and proliferation. This study sheds further light on the potential ability of flavanoids and their gut bacteria derived metabolites to enhance functional β‐cell mass.}, journal={FASEB JOURNAL}, author={Lloyd, Trevor and Griffin, Laura and Krueger, Emily and Beales, Joseph and Barlow, Andrew and Sheets, Jared and Ekpo, Idongesit and Ross, Mimi and Chandra, Preeti and Rathore, Atul and et al.}, year={2020}, month={Apr} }