Reducing cadmium bioavailability from food by protecting the human gut microbiota from cadmium toxicity

Cadmium (Cd), a toxic heavy metal present in many foods, affects the redox status in different organs, causing misregulation of cellular processes, leading to skeletal, renal, gastrointestinal, metabolic, and cognitive disorders. Most healthy individuals only absorb 3-8% of dietary Cd, leaving a majority of Cd to interact with the gut microbiota. In mouse models, Cd negatively affects microbial metabolism and compromises intestinal barrier integrity, leading to increased Cd absorption and associated metabolic complications. Therefore, there is a critical need to reduce Cd absorption from foods and minimize the impact of Cd on the gut microbiota. Our long-term goal is to develop microbiota-based strategies to decrease Cd absorption from food to improve food safety and protect against Cd toxicity.The overall objective of this project is to develop microbiota-based strategies to protect the host from the damaging effects of chronic, low-dose, food-derived Cd exposure. The central hypothesis is that host diet and Cd-tolerant bacteria regulate the vulnerability of the gut microbiota to Cd damage and that dietary fiber or Cd-tolerant bacteria can be used to restore microbiota composition and function to Cd-sensitive microbiotas, thereby decreasing host absorption of dietary Cd and increasing host health. The specific objectives of this project are: 1) determine the role of Cd tolerance of the gut microbiota in mediating Cd accumulation and associated oxidative stress in host tissues; 2) determine the protective effects of Cd-tolerant bacteria in mediating Cd accumulation and associated oxidative stress in host tissues; and 3) identify the role of diet in conferring Cd-tolerance to a microbiome.