Dietary minerals in the gastrointestinal tract: hydroxypolymerisation of aluminium is regulated by luminal mucins

The regulation of mineral absorption in the gastrointestinal tract is poorl y understood. Recent work has identified an intracellular metal-ion transpo rter but considerable evidence suggests that both soluble and mucosally ass ociated luminal metal-binding ligands regulate initial uptake. Molecules ra nging from low molecular weight organic acids to large glycoproteins have b een suggested but a definite role for any such species has remained elusive . Here, a series of analytical techniques, allowing for this wide variation in potential binding ligands, was applied to the study of intestinal conte nts and tissue of rats following different feeding protocols. Aluminium, th at has a low endogenous background and maintains a high concentration in th e gastrointestinal tract, was investigated as a suitable dietary metal with hydrolytic behaviour similar, for example, to copper, iron and zinc. High resolution nuclear magnetic resonance spectroscopy identified a number of e ndogenous low molecular weight weak ligands that are secreted into the inte stinal lumen. These may slow the rate of hydroxy-polymerisation of hydrolyt ic metals, allowing their effective donation to less mobile, higher molecul ar weight binding ligands. Histochemical staining suggested that such speci es may be soluble mucins as these were consistently associated with luminal aluminium. Significantly, this interaction prevented hydroxy/phosphate pre cipitation of aluminium, even at supraphysiological levels of the element. This was confirmed with X-ray micro-analysis investigations of ex vivo lumi nal contents. Nevertheless, from phase distribution experiments, the majori ty (60-95%) of luminal aluminium was associated with the intestinal solid p hase and further histochemistry confirmed this to be gelatinous mucus, chie fly as the mucosally adherent layer. All results suggest a major role for m ucus in regulating the gastrointestinal absorption of aluminium. It is prop osed that, initially, soluble luminal mucus prevents the hydroxy-precipitat ion of hydrolytic metals at intestinal pH, allowing their effective donatio n to the mucus layer. Based on the differing reported metal-mucus interacti ons, elements that bind well to mucus (Al3+, Fe3+), with kinetically slow r ates of ligand exchange (Al3+ < Fe3+) will be less well absorbed than poorl y bound elements with kinetically faster rates of ligand exchange (Cu2+, Zn 2+ etc.). This mechanism would readily explain many of the reported observa tions on mineral availability, including the marked variation in absorption of different elements, the differential effects of dietary ligands on mine ral uptake and the competition for absorption between different metals. (C) 1999 Elsevier Science Inc. All rights reserved.