Intestinal absorption of water-soluble vitamins in health and disease

Abstract

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events.

Figure 1

Schematic depiction of the membrane expression of well-characterized water-soluble vitamin transporters in polarized intestinal epithelial cells

Figure 2. Distribution of hSMVT fused to GFP in human intestinal epithelial Caco-2 cells grown on filters

(A) XY and Z confocal images showing a Caco-2 cell expressing hSMVT–EGFP (enhanced GFP) and DsRed (a cytoplasmic dye) imaged 48 h after transient transfection. The lower panels show distribution of EGFP alone. (B) Western blot showing the expression of hSMVT at human colonic apical (but not basolateral) membrane. Ab, antibody; AMV, apical membrane vesicles. Adapted from The American Journal of Physiology: Cell Physiology, vol. 296 (2010), Subramanian, V.S., Marchant, J.S., Boulware, M.J., Ma, T.Y. and Said, H.M., Membrane targeting and intracellular trafficking of the human sodium-dependent multivitamin transporter in polarized epithelial cells, pp. C663–C671, used with permission from The American Physiological Society.

Figure 3. Co-localization of hRFC with DYNLRB1 in human intestinal epithelial cells

Human intestinal epithelial HuTu-80 cells were grown on glass-bottomed Petri dishes and cotransfected with hRFC–GFP (left-hand panel) and DsRed–DYNLRB1 (middle panel); the right-hand panel is a merged image showing co-localization of hRFC and DYNLRB1 (yellow). Adapted from The American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 297 (2009), Ashokkumar, B., Nabokina, S.M., Ma, T.Y. and Said, H.M., Identification of dynein light chain road block-1 as a novel interaction partner with the human reduced folate carrier, pp. G480–G487, used with permission from The American Physiological Society.

Figure 4. Effect of the loss of THTR-2 on intestinal thiamin uptake

Initial rate of carrier-mediated thiamin uptake in vitro in freshly isolated intestinal epithelial cells (A) and in vivo by intact intestinal loops (B) from THTR-2-knockout mice (THTR-2^−/− ) and their sex-matched littermates [P < 0.01 for (A and B)]. (C) Initial rate of carrier-mediated biotin uptake in vivo by intact intestinal loops from THTR-2^+/+ and THTR-2^−/− mice. Reprinted from Gastroenterology, vol. 138, Reidling, J.C., Lambrecht, N., Kassir, M. and Said, H.M., Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice, pp. 1802–1809, © 2010, with permission from Elsevier.

Figure 5. Expression of hTHTR-1 (A and B) and hTHTR-2 (C and D) fused to GFP in polarized living human intestinal epithelial Caco-2 cells

AP, apical membrane; BL, basolateral membrane. Adapted from The American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 286 (2003), Said, H.M., Balamurugan, K., Subramanian, V.S. and Marchant, J.S., Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine, G491–G498, used with permission from The American Physiological Society.