Prebiotics as modulators of colonic calcium and magnesium uptake

Ca²⁺ and Mg²⁺ are essential nutrients, and deficiency can cause serious health problems. Thus, lack of Ca²⁺ and Mg²⁺ can lead to osteoporosis, with incidence rising both in absolute and age-specific terms, while Mg²⁺ deficiency is associated with type II diabetes. Prevention via vitamin D or estrogen is controversial, and the bioavailability of Ca²⁺ and Mg²⁺ from supplements is significantly lower than that from milk products. Problems are likely to increase as populations age and the number of people on vegan diets surges. Developing new therapeutic strategies requires a better understanding of the molecular mechanisms involved in absorption by intestinal epithelia. The vitamin-D dependent, active pathway for the uptake of Ca²⁺ from the upper small intestine involving TRPV6 is highly efficient but only accounts for about 20% of total uptake. Instead, most Ca²⁺ uptake is thought to occur via passive paracellular diffusion across the ileum, although sufficiently high luminal concentrations are difficult to achieve.. Interestingly, colon and caecum also have a considerable capacity for the active absorption of Ca²⁺ and Mg²⁺, the molecular mechanisms of which are unclear. Intriguingly, stimulating fermentation by prebiotics enhances colonic absorption, which can rise from ~10% to ~30% of the total. Notably, fermentation releases protons, which inhibits channels highly selective for Ca²⁺ and Mg²⁺ (TRPV6 and TRPM6/TRPM7). Conversely, the non-selective cation channel TRPV3 is stimulated by both intracellular acidification and by numerous herbal compounds. Spicy, fiber-rich food, as traditionally consumed in many cultures, might enhance the uptake of Ca²⁺ and Mg²⁺ via this pathway.