Fortifying casein phosphopeptides and Ca in wheat reduces the As, Cd, and Pb bioavailability based on a mouse model: Calcium and phosphate transporters and gut microbiota

Reducing the oral bioavailability of metal contaminants including As, Cd, , and Pb in foods can protect human health. Studies showed reduced metal bioavailability with elevated Ca and Fe intake; however, the effectiveness of enhancing food Ca and Fe bioavailability remains unknown. Based on a mouse bioassay and using metal accumulation in mouse tissues (kidneys and liver) as the bioavailability endpoint, this study investigated the roles of casein phosphopeptides (CPP, food nutrition fortifier) in lowering the As, Cd, and Pb bioavailability from consuming a metal-contaminated wheat. The CPP amendment at 0.10–0.50% in wheat promoted its Ca bioavailability, causing 33–62% and 59–80% decreases in the gene expression encoding for duodenal Ca and phosphate transporters in mice. This limited transcellular transport of Cd²⁺ and inorganic arsenate via Ca and phosphate transporters respectively, thus leading to 27% and 34% decreases in Cd and As contents in mouse kidneys fed with wheat at 0.50% CPP amendment. In addition, CPP promoted the colonization of Feacalibaculum and Bifidobacterium in mouse gut, likely promoting As excretion in feces by 81–112%. In contrast to As, and Cd, CPP failed to reduce Pb contents in mouse tissue after consuming CPP-amended wheat, probably by elevating wheat-Pb solubility in the intestinal fluid by 48–136%. However, co-amendment of 0.30% CPP and 500 ​μg ​g⁻¹ Ca as Ca gluconate lowered the As, Cd, and Pb contents in mouse kidneys by 38–71%. The data indicate that fortifying Ca together with CPP in wheat can reduce human exposure to multi-metals via dietary intake.