Different Cadmium Bioavailability from Wheat and Rice Dictates Toxicity via Distinct Intestinal Pathways in Mice.

Cadmium accumulation in the liver and kidneys was over 2-fold lower in wheat-fed mice compared to rice-fed mice.

• Cd-containing whole wheat and polished rice were fed to mice in a controlled dietary exposure study.
• Liver and kidney Cd accumulation were the primary bioaccumulation endpoints measured.
• The difference was described as 'over 2-fold lower' in wheat-fed compared to rice-fed mice.
• Lower bioaccumulation reflects lower Cd bioavailability from wheat relative to rice.

Higher iron, calcium, and zinc contents in wheat compared to rice contributed to lower expression of corresponding mineral transporters in the duodenum of wheat-fed mice.

• Wheat contained higher levels of iron, calcium, and zinc than polished rice.
• These minerals compete with cadmium for shared transporter pathways in intestinal absorption.
• Lower expression of iron, calcium, and zinc transporters was observed in the duodenum of wheat-fed mice.
• Transporter downregulation is identified as one contributor to reduced Cd bioavailability from wheat.

Fiber-rich wheat caused higher relative abundance of Lactobacillus reuteri in the gut microbiota of wheat-fed mice.

• Whole wheat is fiber-rich compared to polished rice, and dietary fiber is known to modulate gut microbiota composition.
• Increased Lactobacillus reuteri abundance was associated with wheat consumption.
• This microbiota shift was linked to strengthening of intestinal integrity and tight junction expression.
• The mechanism connects dietary fiber content of wheat to host gut health outcomes relevant to Cd absorption.

Wheat feeding promoted fecal Cd excretion and upregulated bile acid metabolism in the gut.

• Increased fecal Cd excretion in wheat-fed mice indicates reduced net intestinal absorption of Cd.
• Bile acid metabolism was upregulated in the gut of wheat-fed mice.
• These effects were associated with the higher Lactobacillus reuteri abundance and improved gut health.
• Both fecal excretion and bile acid metabolism changes contributed collectively to lower wheat-Cd bioavailability.

Transporter downregulation and gut health improvements collectively contributed to lower Cd bioavailability from wheat compared to rice.

• Two distinct intestinal pathways were identified: (1) competitive inhibition via mineral transporter downregulation and (2) microbiota-mediated intestinal integrity enhancement.
• The study used whole wheat versus polished rice as the dietary matrices, representing common human staple food forms.
• Both mechanisms were found to operate simultaneously in wheat-fed mice.
• The findings support the conclusion that 'Cd-containing wheat may pose remarkably lower health risk to humans compared to rice.'