Molecular Mechanism of the Effect of Fructooligosaccharides on Calcium Absorption

Abstract

Previous reports have demonstrated through the use of animal models that dietary fructooligosaccharides (FOS) exert stimulatory effects on the absorption of the minerals; calcium, magnesium, and iron. Recently, these effects were also clinically confirmed in humans. This paper reviews studies that used the techniques of molecular biology to elucidate the mechanisms by which FOS stimulates calcium absorption for which the small intestine has long been considered a primary site. However, Ohta et al. reported that the large intestine, and the cecum in particular, has an important role. This conclusion was based on the observation that the stimulatory effect of FOS on calcium absorption was not observed in cecectomized rats. The contribution of paracellular and transcellular paths was suggested for the stimulation caused by FOS. Transcellular transport is a multistep process comprising several components and is under the regulation of vitamin D. One component is calbindin-D9k (CaBP), a calcium binding protein. The upstream region of the CaBP gene was analyzed, and a responsive sequence for vitamin D receptor was identified. Mucosal cells were then obtained from FOS-fed rats, and the expression of CaBP protein and mRNA were determined. Dietary FOS decreased the expression of CaBP in the small intestine, but resulted in increased levels in the cecum and colorectum. Since protein and mRNA both demonstrated similar patterns of expression, the effects of FOS can be seen to affect CaBP at the transcription level. Furthermore, the changes in CaBP expression were proportional to both the level of apparent calcium absorption and the amount of FOS ingested. This means that the increase of calcium absorption induced by FOS comprises paracellular and CaBP-mediated transcellular transport. In a hypothetical model, short-chain organic acids produced from FOS by fermentation were proposed as key elements to regulate both the paracellular and the transcellular transport of calcium. However, the molecular mechanisms of this regulation have not yet been clarified.