Iron Supplements Containing Lactobacillus plantarum 299v Increase Ferric Iron and Up-regulate the Ferric Reductase DCYTB in Human Caco-2/HT29 MTX Co-Cultures

Several human interventions have indicated that Lactobacillus plantarum 299v (L. plantarum 299v) increases intestinal iron absorption. The aim of the present study was to investigate possible effects of L. plantarum 299v on the mechanisms of iron absorption on the cellular level. We have previously shown that lactic fermentation of vegetables increased iron absorption in humans. It was revealed that the level of ferric iron [Fe (H2O)5]2+ was increased after fermentation. Therefore, we used voltammetry to measure the oxidation state of iron in simulated gastrointestinal digested oat and mango drinks and capsule meals containing L. plantarum 299v. We also exposed human intestinal co-cultures of enterocytes and goblet cells (Caco-2/HT29 MTX) to the supplements in order to study the effect on proteins possibly involved (MUC5AC, DCYTB, DMT1, and ferritin). We detected an increase in ferric iron in the digested meals and drinks containing L. plantarum 299v. In the intestinal cell model, we observed that the ferric reductase DCYTB increased in the presence of L. plantarum 299v, while the production of mucin (MUC5AC) decreased independently of L. plantarum 299v. In conclusion, the data suggest that the effect of L. plantarum 299v on iron metabolism is mediated through driving the Fe3+/DCYTB axis.

[1]  N. Roy,et al.  Metabolism of Caprine Milk Carbohydrates by Probiotic Bacteria and Caco-2:HT29–MTX Epithelial Co-Cultures and Their Impact on Intestinal Barrier Integrity , 2018, Nutrients.

[2]  L. Hulthén,et al.  Freeze-dried Lactobacillus plantarum 299v increases iron absorption in young females—Double isotope sequential single-blind studies in menstruating women , 2017, PloS one.

[3]  Jesús Martín,et al.  Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption. , 2017, Food chemistry.

[4]  Manuela M. Santos,et al.  Iron Supplements Modulate Colon Microbiota Composition and Potentiate the Protective Effects of Probiotics in Dextran Sodium Sulfate-induced Colitis , 2017, Inflammatory bowel diseases.

[5]  Efsa Panel on Dietetic Products Lactobacillus plantarum 299v and an increase of non-haem iron absorption: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 , 2016 .

[6]  L. Hulthén,et al.  Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age , 2015, British Journal of Nutrition.

[7]  N. Scheers,et al.  Increased iron bioavailability from lactic-fermented vegetables is likely an effect of promoting the formation of ferric iron (Fe3+) , 2015, European Journal of Nutrition.

[8]  M. F. Aslam,et al.  Caco-2 Cell Acquisition of Dietary Iron(III) Invokes a Nanoparticulate Endocytic Pathway , 2013, PloS one.

[9]  P. Trost,et al.  Cytochromes b561: ascorbate-mediated trans-membrane electron transport. , 2013, Antioxidants & redox signaling.

[10]  M. McGuckin,et al.  Gastrointestinal Cell Lines Form Polarized Epithelia with an Adherent Mucus Layer when Cultured in Semi-Wet Interfaces with Mechanical Stimulation , 2013, PloS one.

[11]  A. Shawki,et al.  Substrate Profile and Metal-ion Selectivity of Human Divalent Metal-ion Transporter-1* , 2012, The Journal of Biological Chemistry.

[12]  M. Alminger,et al.  Determination of Fe2+ and Fe3+ in Aqueous Solutions Containing Food Chelators by Differential Pulse Anodic Stripping Voltammetry , 2010 .

[13]  Gretchen J. Mahler,et al.  Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell culture model used to predict iron bioavailability. , 2009, The Journal of nutritional biochemistry.

[14]  N. Scheers,et al.  Ascorbic acid uptake affects ferritin, Dcytb and Nramp2 expression in Caco-2 cells , 2008, European journal of nutrition.

[15]  I. Tetens,et al.  Viable, lyophilized lactobacilli do not increase iron absorption from a lactic acid-fermented meal in healthy young women, and no iron absorption occurs in the distal intestine , 2007, British Journal of Nutrition.

[16]  I. Tetens,et al.  A lactic acid-fermented oat gruel increases non-haem iron absorption from a phytate-rich meal in healthy women of childbearing age , 2006, British Journal of Nutrition.

[17]  N. Andrews,et al.  Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. , 2005, Blood.

[18]  M. Hentze,et al.  Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: Implications for regulation and cellular function , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R J Simpson,et al.  An Iron-Regulated Ferric Reductase Associated with the Absorption of Dietary Iron , 2001, Science.

[20]  S. Srai,et al.  Nramp2 Expression Is Associated with pH-dependent Iron Uptake across the Apical Membrane of Human Intestinal Caco-2 Cells* , 2000, The Journal of Biological Chemistry.

[21]  M. Hollingsworth,et al.  Probiotics inhibit enteropathogenic E. coliadherence in vitro by inducing intestinal mucin gene expression. , 1999, American journal of physiology. Gastrointestinal and liver physiology.

[22]  M. Conrad,et al.  A role for mucin in the absorption of inorganic iron and other metal cations. A study in rats. , 1991, Gastroenterology.