Recipient Organization
UNIVERSITY OF NEBRASKA
(N/A)
LINCOLN,NE 68583
Performing Department
Food Science & Technology
Non Technical Summary
Cadmium (Cd), a toxic heavy metal present in many foods, affects redox status in different organs, causing misregulation of cellular processes, leading to skeletal, renal, gastrointestinal, metabolic, and cognitive disorders. Cd has differential effects on the gut microbiome, which regulates Cd bioavailability, with altered metabolite pools of lactate and butyrate in Cd-sensitive microbiomes. The overall objective of this proposal is to develop microbiota-based strategies that protect the host from Cd toxicity. We hypothesize 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 restore composition and function to Cd-sensitive microbiotas, thereby decreasing host absorption of Cd and increasing host health. We will employ human microbiota-associated mice harboring microbiotas that differ in Cd sensitivity to determine the role of 1) Cd tolerance of the gut microbiota and 2) Cd-tolerant bacteria, in mediating Cd accumulation and oxidative stress in host tissues. We will also identify the role of diet in conferring Cd tolerance to a microbiome by examining the protective effect of dietary fiber on the gut microbiota against Cd toxicity. This project addresses the priority areas of this AFRI program by investigating the ternary interrelationship among foods, Cd, and the human gut microbiome. We will link the functional outcomes of metabolites of the gut microbiome to outcomes that are relevant to human health, including decreasing Cd deposition and oxidative stress in host tissues. Our study will help shape dietary recommendations to protect the public from Cd toxicity.
Animal Health Component
30%
Research Effort Categories
Basic
70%
Applied
30%
Developmental
0%
Goals / Objectives
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.
Project Methods
Objective 1 will determine the uptake of Cd into host tissues in human microbiota-associated mice harboring microbiotas that differ in their susceptibility to Cd. Our innovative approach will be the first study to employ human microbiomes in an animal model where mice are consuming diets that differ in dietary Cd from food that is equivalent to the Cd intake of the average American. Based on results from prior studies, C57BL/6 mice represent a tractable model for Cd-microbiota interactions and host Cd uptake.Objective 2 will examine the efficacy of Cd-tolerant bacteria to diminish Cd accumulation in host tissues. The Cd-tolerant bacteria isolate that we will use will be human gut-derived, pre-selected based on Cd-tolerance and demonstrated ability to work synergistically with a Cd-susceptible microbiome to increase butyrate production even in the presence of Cd. This study will establish a strategy to mitigate Cd-toxicity in individuals harboring Cd-susceptible microbiomes.Objective 3 attempts to uncover the underlying cause of Cd-tolerance of a microbiome by culturing Cd-tolerant and Cd-sensitive microbiomes in Cd-containing medium that differs in carbohydrate (i.e., dietary fiber) concentration. Understanding why some microbiomes are Cd-tolerant and others are Cd-sensitive may help shape dietary recommendations to protect the public from the damaging effects of Cd.