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Oral administration of Bifidobacterium longum CECT 7347 ameliorates gliadin-induced alterations in liver iron mobilisation

  • José Moisés Laparra (a1), Marta Olivares (a1) and Yolanda Sanz (a1)

Abstract

Coeliac disease is an autoimmune disorder triggered by gluten intake, causing intestinal inflammation and mucosal damage commonly associated with the malabsorption of nutrients and ferropenic anaemia. The present study evaluates the effects of the oral administration of Bifidobacterium longum CECT 7347 on gliadin-mediated alterations in hepatic Fe deposition and Hb concentration, liver transferrin receptor (TfR)-2, IL-6, TNF-α and hepcidin (Hamp) expression (mRNA), and active hepcidin peptide production by liquid chromatography–MS/MS. Weanling rats, sensitised or not with interferon (IFN)-γ, were fed with gliadins and/or the bifidobacterial strain. Gliadin feeding increased hepatic Fe deposition; however, only gliadin-fed sensitised animals showed lower Hb concentrations than the controls. TfR2 expression decreased after gliadins were fed to both sensitised and non-sensitised animals, and restored by the administration of B. longum. These observations were accompanied by increases in IL-6 expression levels in all the treatment groups; however, TNF-α expression only increased significantly in animals fed gliadins alone or together with B. longum if they had previously been sensitised with IFN-γ. Liver expression levels of Hamp diminished in all cases to the lowest values in animals sensitised with IFN-γ after being fed with gliadins and/or bifidobacteria. In these animals, plasma Hamp active peptide concentrations significantly increased when compared with the controls. Significant correlations were calculated between Hamp expression and liver Fe contents (liver Fe = 1/0·0032+0·032 × Hampexp), and Hb concentrations (Hb = 11·49+10·13 × (Hampexp)1/2). These data indicate that oral administration of B. longum ameliorates gliadin-mediated perturbations in liver Fe deposition and mobilisation.

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Corresponding author

*Corresponding author: J. M. Laparra, fax +34 963 636 301, email mlaparra@iata.csic.es

References

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1Schuppan, D, Junker, Y & Barisani, D (2009) Celiac disease: from pathogenesis to novel therapies. Gastroenterology 137, 19121933.
2Romaldini, CC, Barbieri, D, Okay, TS, et al. (2002) Serum soluble interleukin-2 receptor, interleukin-6 and tumor necrosis factor-alpha in children with celiac disease: response to treatment. J Pediatr Gastroenterol Nutr 35, 513517.
3Dema, B, Martínez, A, Fernández-Arquero, M, et al. (2009) The IL6-174G/C polymorphism is associated with celiac disease susceptibility in girls. Hum Immunol 70, 191194.
4Jelínková, L, Tuckova, L, Cinová, J, et al. (2004) Gliadin stimulates human monocytes to production of IL-8 and TNFα through a mechanism involving NFkB. FEBS Lett 571, 8185.
5Bemelmans, MH, Abramowicz, D, Gouma, DJ, et al. (1994) In vivo T cell activation by anti-CD3 monoclonal antibody induces soluble TNF receptor release in mice. Effects of pentoxifylline, methylprednisolone, anti-TNF, and anti-IFN-gamma antibodies. J Immunol 153, 499506.
6Naka, T, Nishimoto, N & Kishimoto, T (2002) The paradigm of IL-6: from basic science to medicine. Arthritis Res 4, S233S242.
7Medina, M, De Palma, G, Ribes-Koninckx, C, et al. (2008) Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients. J Inflamm (Lond) 5, 19.
8Sánchez, E, De Palma, G, Capilla, A, et al. (2011) Influence of environmental and genetic factors linked to celiac disease risk on infant gut colonization by Bacteroides species. Appl Environ Microbiol 77, 53165323.
9Nadal, I, Donat, E, Ribes-Koninckx, C, et al. (2007) Imbalance in the composition of the duodenal microbiota of children with celiac disease. J Med Microbiol 56, 16691674.
10Collado, MC, Donat, E, Ribes-Koninckx, C, et al. (2009) Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol 62, 264269.
11Laparra, JM & Sanz, Y (2010) Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion. J Cell Biochem 109, 801807.
12Laparra, JM, Olivares, M, Gallina, O, et al. (2012) Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model. PLoS One 7, e30744.
13Olivares, M, Laparra, M & Sanz, Y (2011) Influence of Bifidobacterium longum CECT 7347 and gliadin peptides on intestinal epithelial cell proteome. J Agric Food Chem. 59, 76667671.
14Hernandez, L & Green, PH (2006) Extraintestinal manifestations of celiac disease. Curr Gastroenterol Rep 8, 383389.
15Ludvigsson, JF, Brandt, L & Montgomery, SM (2009) Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa. BMC Gastroenterol 9, 57.
16Ganong, WF (1990) Bases neuronales de la conducta instintiva y de las emociones (Neural basis of instinctual behaviour and emotions). In Fisiología médica (Review of Medical Physiology). Mexico, DF: El Manual Moderno, SA de CV.
17Johnson, D, Bayele, H, Johnston, K, et al. (2004) Tumour necrosis factor alpha regulates iron transport and transporter expression in human intestinal epithelial cells. FEBS Lett 573, 195201.
18Kobune, M, Kohgo, Y, Kato, J, et al. (1994) Interleukin-6 enhances hepatic transferrin uptake and ferritin expression in rats. Hepatology 19, 14681475.
19Hirayama, M, Kohgo, Y, Kondo, H, et al. (1993) Regulation of iron metabolism in HepG2 cells: a possible role for cytokines in the hepatic deposition of iron. Hepatology 18, 874880.
20Ganz, T (2003) Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 102, 783788.
21De Domenico, I, Zhang, TY, Koening, CL, et al. (2010) Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest 120, 23952405.
22Rodrigo, L (2006) Celiac disease. World J Gastroenterol 12, 65856593.
23Greger, JL (1992) Using animals to assess bioavailability of minerals: implications for human nutrition. J Nutr 122, 20472052.
24Corpet, DE & Pierre, F (2005) How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men. Eur J Cancer 41, 19111922.
25Alférez, MJ, Díaz-Castro, J, López-Aliaga, I, et al. (2011) Development of nutritional iron deficiency in growing male rats: haematological parameters, iron bioavailability and oxidative defence. Br J Nutr 105, 517525.
26Jenkitkasemwong, S, Broderius, M, Nam, H, et al. (2010) Anemic copper-deficient rats, but not mice, display low hepcidin expression and high ferroportin levels. J Nutr 140, 723730.
27Pigeon, C, Ilyin, G, Courselaud, B, et al. (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276, 78117819.
28Dostal, A, Chassard, C, Hilty, FM, et al. (2012) Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J Nutr 142, 271277.
29Andrews, SC, Robinson, AK & Rodriguez-Quinones, F (2003) Bacterial iron homeostasis. FEMS Microbiol Rev 27, 215237.
30Cinova, J, De Palma, G, Stepankova, R, et al. (2011) Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats. PLoS One 6, e16169.
31Livak, KJ & Schmittgen, TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔC T method. Methods 25, 402408.
32Murphy, AT, Witcher, DR, Luan, P, et al. (2007) Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry. Blood 110, 10481054.
33Kroot, JJ, Kemna, EH, Bansal, SS, et al. (2009) Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization. Haematologica 94, 17481752.
34Park, CH, Valore, EV, Waring, AJ, et al. (2001) Hepcidin: a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276, 78067810.
35Hin, H, Bird, G, Fisher, P, et al. (1999) Coeliac disease in primary care: case finding study. BMJ 318, 164167.
36Young, MF, Glahn, RP, Ariza-Nieto, M, et al. (2009) Serum hepcidin is significantly associated with iron absorption from food and supplemental sources in healthy young women. Am J Clin Nutr 89, 533538.
37Zhang, X & Rovin, BH (2010) Hepcidin expression by human monocytes in response to adhesion and pro-inflammatory cytokines. Biochim Biophys Acta 1800, 12621267.
38Fleming, RE (2009) Iron sensing as a partnership: HFE and transferring receptor 2. Cell Metab 9, 211212.
39Dallalio, G, Fleury, T & Means, RT (2003) Serum hepcidin in clinical specimens. Br J Haematol 122, 9961000.
40Kemna, EH, Tjalsma, H, Podust, VN, et al. (2007) Mass spectrometry based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem 53, 620628.
41Nemeth, E, Rivera, S, Gabayan, V, et al. (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113, 12711276.
42Lotz, M, Jirik, F, Kabouridis, R, et al. (1988) BSF-2/IL-6 is costimulant for human thymocytes and T lymphocytes. J Exp Med 167, 12531258.
43Nicola, NA, Metcalf, D, Matsumoto, M, et al. (1983) Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem 258, 90179023.
44Jacolot, S, Férec, C & Mura, C (2008) Iron responses in hepatic, intestinal and macrophage/monocyte cell lines under different culture conditions. Blood Cells Mol Dis 41, 100108.
45Hoffman, RA (2000) Intraepithelial lymphocytes coinduce nitric oxide synthase in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 278, G886G894.

Keywords

Oral administration of Bifidobacterium longum CECT 7347 ameliorates gliadin-induced alterations in liver iron mobilisation

  • José Moisés Laparra (a1), Marta Olivares (a1) and Yolanda Sanz (a1)

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