Cadmium oral bioavailability: From intestinal transport mechanisms to microplastic Co-exposure

Cadmium (Cd) entry into the circulation is at least a two-step process. The initial step involves Cd binding to apically expressed transporters of essential metals, including Fe, Ca, Zn, Cu, and Mg. Microplastics (MPs) and nanoplastics (NPs) can adsorb Cd onto their surfaces, thereby increasing its bioavailability. In contrast, the subsequent transport of Cd across the basolateral membrane appears equally important but remains far less studied. Among the proposed transporters, ZnT1 and ATP7A are the most promising candidates for mediating Cd efflux into the circulation. Factors influencing oral Cd bioavailability can be classified as preintestinal, intestinal, or postintestinal. The most important preintestinal determinants are inadequate dietary intake of essential metals such as Fe, Cu, Zn, Mg, and Ca, whereas postintestinal factors primarily involve systemic deficiencies of these elements. Additional contributors include high phytate intake, low dietary fiber consumption, co-exposure to MPs capable of adsorbing Cd, and the absence of protective strategies such as Ca biofortification. Furthermore, alterations in the gut microbiota that compromise intestinal barrier integrity facilitate Cd uptake, while intestinal pH influences Cd binding to dietary components and consequently its fecal elimination.