Antibiotics have been widely used not only in humans but also in animals for growth promotion and infectious disease control. Antibiotic resistance is defined as the microbial ability to sustain and multiply in the presence of antibiotics. Antibiotic resistance is ancient and ubiquitous in environmental microbes, particularly soils where many antibiotics have been discovered so far, and this original resistance is viewed as intrinsic resistance. Nevertheless, the intensive use of antibiotics in humans and animals have undoubtedly increased the emergence and abundance of antibiotic resistance in the environment, and therefore threatening global human health. Numerous studies now have demonstrated that the amounts of antibiotics use and residual discharge into the environment is well correlated with the abundance of antibiotic resistance, and antibiotic resistance can spread via not only vertical gene transfer but also horizontal gene transfer (HGT), and eventually to human pathogens, and even the emergence of superbugs. In 2006 Pruden et al. explicitly proposed antibiotic resistance as emerging contaminants, and suggested that conventional environmental treatment systems were not designed to remove these emerging contaminants. This talk will first discuss the major sources of environmental antibiotic resistome-urban waste water system vs. intensive animal farming. Subsequently the talk will discuss the major pathways of the emission of antibiotic resistance genes to the environment (soil and water). Thirdly the talk will take China as an example to investigate the pollution status of antibiotic resistance genes in soils, rivers and estuaries. Finally, potential mitigation measures will be discussed. Throughout the talk, divers molecular tools and "omics" approaches characterizing the environmental antibiotic resistome will be highlighted.

Epidemiological evidence across various populations supports the notion that diets high in fruits and vegetables are associated with a decreased risk of chronic disease and overall mortality¹. Additionally, clinical studies have shown that diets high in polyphenols can improve risk factors for cardiovascular disease and neurodegenerative processes. Mechanisms of action have been postulated including the ability of select polyphenols to modify oxidative and inflammatory stress, impact gut microbial communities, and positively alter functional endpoints including blood flow and cognitive performance. With such promise, interest in the physiological delivery (bioavailability) of polyphenols and their metabolites to target tissues from foods has grown. Polyphenol bioavailability has been the subject of intense investigation. Prevailing opinion is that absorption of polyphenols is generally poor and modified by several factors including (1) chemical form of the polyphenol and composition of the food matrix; (2) potential sensitivity to intestinal conditions; (3) poor intestinal transport; (4) metabolism by mammalian and bacterial systems and (5) rapid excretion from the body². As evidence mounts for a health-protective role for dietary polyphenols, the importance of understanding factors that can improve bioavailability of these compounds has increased. This lecture will present data from our past and ongoing efforts focused on understanding food matrix and select physiological factors that impact absorption, metabolism and tissue distribution of flavan-3-ols, a main dietary polyphenol class.

Through a combination of preclinical (in vitro digestion/Caco-2 intestinal cell and animal models) as well as clinical studies we have investigated the role of food form and formulation on digestive stability, bioaccessibility and bioavailability of flavan-3-ols from tea, cocoa and grape. Macro and micronutrient interactions within the food matrix were found to impact digestive stability and intestinal transport of flavan-3-ol from tea, cocoa and grape products. Co-formulation of tea and cocoa with ascorbic acid and carbohydrate were found to positively influence flavan-3-ol bioavailability while protein incorporation only had a modest impact to overall absorption in both animal models^3,4 and humans⁵ despite the ability to enhance stability of flavan-3-ols. These results suggest that product formulation strategies can be leveraged to enhance acute absorption and potentially metabolism of flavan-3-ols from foods. In consideration of the complexity of long-term dietary patterns, we also investigated the impact of background diet (high versus low fat), repeated exposure (10 days or greater) and presence of risk factors (obesity and diabetes) on grape derived flavan-3-ol bioavailability and metabolism. While background diet did not influence polyphenol absorption⁶, clear differences were observed in lean versus obese animal models and volunteers^7,8. Furthermore, evidence of an adaptation in absorption and metabolism of polyphenols during periods of repeated exposure was observed with an increase in flavan-3-ol bioavailability for rodents⁹ and humans⁸ over a 10-day repeated exposure to grape polyphenols. Metabolism of flavan-3-ols was also impacted with an increase in glucuronidation but not methylation of monomeric forms observed¹⁰. Mechanisms were explored using the Caco-2 human intestinal cell model and suggest an enhancement of trans-epithelial transport over time as a result of adaptation in select xenobiotic and metabolizing genes (COMT, ABCC2 and ABCB1) from exposure to flavan-3-ols form green tea and grape seed extracts¹¹. Overall, these results suggest that both food and physiological factors can alter bioavailability and metabolism of polyphenols from diets and, that adaptation to polyphenol exposure must be considered when studying metabolite profiles and their association to disease risk and outcomes. Finally, understanding how food matrix and physiological factors can impact polyphenol bioavailability and metabolism will allow for the design of foods and diets consistent with delivery of bioactive polyphenols and their desired health benefits in target populations.

Acknowledgments
Funding for these studies was provided by the NIH, NSF and USDA

References
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