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Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

  • Carmen Villodre Tudela (a1), Christelle Boudry (a2), Friederike Stumpff (a3), Jörg R. Aschenbach (a3), Wilfried Vahjen (a1), Jürgen Zentek (a1) and Robert Pieper (a1)...

Abstract

The present study investigated the influence of bacterial metabolites on monocarboxylate transporter 1 (MCT1) expression in pigs using in vivo, ex vivo and in vitro approaches. Piglets (n 24) were fed high-protein (26 %) or low-protein (18 %) diets with or without fermentable carbohydrates. Colonic digesta samples were analysed for a broad range of bacterial metabolites. The expression of MCT1, TNF-α, interferon γ (IFN-γ) and IL-8 was determined in colonic tissue. The expression of MCT1 was lower and of TNF-α and IL-8 was higher with high-protein diets (P< 0·05). MCT1 expression was positively correlated with l-lactate, whereas negatively correlated with NH3 and putrescine (P< 0·05). The expression of IL-8 and TNF-α was negatively correlated with l-lactate and positively correlated with NH3 and putrescine, whereas the expression of IFN-γ was positively correlated with histamine and 4-ethylphenol (P< 0·05). Subsequently, porcine colonic tissue and Caco-2 cells were incubated with Na-butyrate, NH4Cl or TNF-α as selected bacterial metabolites or mediators of inflammation. Colonic MCT1 expression was higher after incubation with Na-butyrate (P< 0·05) and lower after incubation with NH4Cl or TNF-α (P< 0·05). Incubation of Caco-2 cells with increasing concentrations of these metabolites confirmed the up-regulation of MCT1 expression by Na-butyrate (linear, P< 0·05) and down-regulation by TNF-α and NH4Cl (linear, P< 0·05). The high-protein diet decreased the expression of MCT1 in the colon of pigs, which appears to be linked to NH3- and TNF-α-mediated signalling.

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Corresponding author

* Corresponding author: R. Pieper, fax +49 3 838 55938, email robert.pieper@fu-berlin.de

References

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1 Blaut, M & Clavel, T (2007) Metabolic diversity of the intestinal microbiota: implication for health and disease. J Nutr 137, 751755.
2 Hamer, HM, De Preter, V, Windey, K, et al. (2012) Functional analysis of colonic bacterial metabolism: relevant to health? Am J Physiol Gastrointest Liver Physiol 302, G1G9.
3 Windey, K, De Preter, V & Verbeke, K (2012) Relevance of protein fermentation to the gut health. Mol Nutr Food Res 56, 184196.
4 Rist, VTS, Weiss, E, Eklund, M, et al. (2013) Impact of dietary protein on microbiota composition and activity in the gastrointestinal tract of piglets in relation to gut health: a review. Animal 7, 10671078.
5 Wellock, IJ, Fortomaris, PD, Houdijk, JGM, et al. (2008) Effects of dietary protein supply, weaning age and experimental enterotoxigenic Escherichia coli infection on newly weaned pigs: health. Animal 2, 834842.
6 Opapeju, FO, Krause, DO, Payne, RL, et al. (2009) Effect of dietary protein level on growth performance, indicators of enteric health, and gastrointestinal microbial ecology of weaned pigs induced with postweaning colibacillosis. J Anim Sci 87, 26352643.
7 De Lange, CFM, Pluske, J, Gong, J, et al. (2010) Strategic use of feed ingredients and feed additives to stimulate gut health and development in young pigs. Livest Sci 134, 124134.
8 Heo, JM, Opapeju, FO, Pluske, JR, et al. (2013) Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds. J Anim Physiol Anim Nutr 97, 207237.
9 Plöger, S, Stumpff, F, Penner, GB, et al. (2012) Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann N Y Acad Sci 1258, 5259.
10 Metzler-Zebeli, BU, Gänzle, MG, Mosenthin, R, et al. (2012) Oat β-glucan and dietary calcium and phosphorus differentially modify intestinal expression of proinflammatory cytokines and monocarboxylate transporter 1 and cecal morphology in weaned pigs. J Nutr 142, 668674.
11 Haenen, D, Zhang, J, Souza da Silva, C, et al. (2013) A diet high in resistant starch modulates microbiota composition, SCFA concentrations, and gene expression in pig intestine. J Nutr 143, 274283.
12 Ritzhaupt, A, Wood, IS, Ellis, A, et al. (1998) Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport l-lactate as well as butyrate. J Physiol 513, 719732.
13 Cuff, MA, Lambert, DW & Shirazi-Beechey, SP (2002) Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. J Physiol 539, 361371.
14 Borthakur, A, Saksena, S, Gill, RK, et al. (2008) Regulation of monocarboxylate transporter 1 (MCT1) promoter by butyrate in human intestinal epithelial cells: involvement of NF-κB pathway. J Cell Biochem 103, 14521463.
15 Lambert, DW, Wood, IS, Ellis, A, et al. (2002) Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy. Br J Cancer 86, 12621269.
16 Thibault, R, de Coppet, P, Daly, K, et al. (2007) Down-regulation of the monocarboxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology 133, 19161927.
17 Pieper, R, Kröger, S, Richter, JF, et al. (2012) Fermentable fiber ameliorates fermentable protein-induced changes in microbial ecology, but not the mucosal response, in the colon of piglets. J Nutr 142, 661667.
18 Kröger, S, Pieper, R, Schwelberger, HG, et al. (2013) Diets high in heat-treated soybean meal reduce the histamine-induced epithelial response in the colon of weaned piglets and increase epithelial catabolism of histamine. PLOS ONE 8, e80612.
19 Richter, JF, Pieper, R, Zakrzewski, SS, et al. (2014) Diets high in fermentable protein and fiber alter tight junction protein composition with minor effects on barrier function in piglet colon. Br J Nutr 111, 10401049.
20 Gesellschaft für Ernährungsphysiologie (2006) Empfehlungen zur Energie und Nährstoffversorgung von Schweinen (Recommendations on Energy and Nutrient Supply of Pigs). Frankfurt am Main: DLG-Verlag.
21 Naumann, K & Bassler, R (2004) Methodenbuch Band III: Die chemische Untersuchung von Futtermitteln (Methods Book Volume III: The Chemical Control of Feedingstuffs). Melsungen: Neumann-Neudamm.
22 Pieper, R, Boudry, C, Bindelle, J, et al. (2014) Interaction between dietary protein content and the source of carbohydrates along the gastrointestinal tract of weaned piglets. Arch Anim Nutr 68, 263280.
23 Pieper, R, Neumann, K, Kröger, S, et al. (2012) Influence of fermentable carbohydrates or protein on large intestinal and urinary metabolomic profiles in piglets. J Anim Sci 90, 3436.
24 Martin, L, Pieper, R, Schunter, N, et al. (2013) Performance, organ zinc concentration, jejunal brush border membrane enzyme activities and mRNA expression in piglets fed with different levels of dietary zinc. Arch Anim Nutr 67, 248261.
25 Pfaffl, MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29, e45.
26 Woodward, AD, Regmi, PR, Gänzle, MG, et al. (2012) Slowly digestible starch influences mRNA abundance of glucose and short-chain fatty acid transporters in the porcine distal intestinal tract. J Anim Sci 90, 8082.
27 Ritzhaupt, A, Ellis, A, Hosie, KB, et al. (1998) The characterization of butyrate transport across pig and human colonic luminal membrane. J Physiol 507, 819830.
28 Gill, RK & Dudeja, PK (2011) A novel facet to consider for the effects of butyrate on its target cells. Focus on The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein. Am J Physiol Cell Physiol 301, C977C979.
29 Daly, K & Shirazi-Beechey, SP (2006) Microarray analysis of butyrate regulated genes in colonic epithelial cells. DNA Cell Biol 25, 4962.
30 Anguita, M, Gasa, J, Nofrarias, M, et al. (2007) Effect of coarse ground corn, sugar beet pulp and wheat bran on the voluntary intake and physicochemical characteristics of digesta of growing pigs. Livest Sci 107, 182191.
31 Molist, F, Gómez de Segura, A, Gasa, J, et al. (2009) Effects of the insoluble and soluble dietary fiber on the physicochemical properties of digesta and the microbial activity in early weaned piglets. Anim Feed Sci Technol 149, 346353.
32 Smith, EA & Macfarlane, GT (1997) Dissimilatory amino acid metabolism in human colonic bacteria. Anaerobe 3, 327337.
33 Lührs, H, Gerke, T, Schauber, J, et al. (2001) Cytokine-activated degradation of inhibitory κB protein α is inhibited by the short-chain fatty acid butyrate. Int J Colorectal Dis 16, 195201.
34 Yin, L, Laevsky, G & Giardina, C (2001) Butyrate suppression of colonocyte NF-κB activation and cellular proteasome activity. J Biol Chem 276, 4464144646.
35 Nofrarías, M, Martínez-Puig, D, Pujols, J, et al. (2007) Long-term intake of resistant starch improves colonic mucosal integrity and reduces gut apoptosis and blood immune cells. Nutrition 23, 861870.
36 Hughes, R, Magge, EAM & Bingham, S (2000) Protein degradation in the large intestine: relevance to colorectal cancer. Curr Issues Intest Microbiol 1, 5158.
37 Attene-Ramos, MS, Wagner, ED, Plewa, MJ, et al. (2006) Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res 4, 914.
38 Blachier, F, Mariotti, F, Huneau, JF, et al. (2007) Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 33, 547562.
39 Darcy-Vrillon, B, Cherbuy, C, Morel, MT, et al. (1996) Short chain fatty acid and glucose metabolism in isolated pig colonocytes: modulation by NH4 + . Mol Cell Biochem 156, 145151.
40 Nancey, S, Moussata, D, Graber, I, et al. (2005) Tumor necrosis factor α reduces butyrate oxidation in vitro in human colonic mucosa: a link from inflammatory process to mucosal damage? Inflamm Bowel Dis 11, 559566.

Keywords

Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

  • Carmen Villodre Tudela (a1), Christelle Boudry (a2), Friederike Stumpff (a3), Jörg R. Aschenbach (a3), Wilfried Vahjen (a1), Jürgen Zentek (a1) and Robert Pieper (a1)...

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