@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={Flavanols are metabolized by the gut microbiota to bioavailable metabolites, and the absorbed fraction is excreted primarily via urine. Uroepithelial cells are thus a potential site of activity due to exposure to high concentrations of these compounds. Chemoprevention by flavanols may be partly due to these metabolites. In Vitro work in this area relies on a limited pool of commercially available microbial metabolites, and little has been done in bladder cancer. The impact of physiologically relevant mixtures of flavanols and their metabolites remains unknown. Rats were fed various flavanols and urine samples, approximating the bioavailable metabolome, were collected. Urines were profiled by UPLC-MS/MS, and their anti-proliferative activities were assayed In Vitro in four bladder cancer models. Significant interindividual variability was observed for composition and proliferation. Microbial metabolite concentrations (valerolactones, phenylalkyl acids and hippuric acids) were positively associated with reduced bladder cancer proliferation In Vitro, while native flavanols were poorly correlated with activity. These results suggest that microbial metabolites may be responsible for chemoprevention in uroepithelial cells following flavanol consumption. This highlights the potential to use individual genetics and microbial metabotyping 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} }