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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 12/2017

01-12-2017 | Original Article

Repeated Oral Exposure to N ε-Carboxymethyllysine, a Maillard Reaction Product, Alleviates Gut Microbiota Dysbiosis in Colitic Mice

Authors: Nesreen ALJahdali, Pascale Gadonna-Widehem, Carine Delayre-Orthez, David Marier, Benjamin Garnier, Franck Carbonero, Pauline M. Anton

Published in: Digestive Diseases and Sciences | Issue 12/2017

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Abstract

Background

Diet is suggested to participate in the etiology of inflammatory bowel diseases (IBD). Repeated exposure to Maillard reaction products (MRPs), molecules resulting from reduction reactions between amino acids and sugars during food heating, has been reported to be either potentially detrimental or beneficial to health.

Aims

The aim of this study is to determine the effect of repeated oral ingestion of N ε-carboxymethyllysine (CML), an advanced MRP, on the onset of two models of experimental IBD and on the gut microbiota composition of mice.

Methods

Mice received either saline (control) or N ε-carboxymethyllysine daily for 21 days. For the last week of treatment, each group was split into subgroups, receiving dextran sulfate sodium salt (DSS) or trinitrobenzenesulfonic acid (TNBS) to induce colitis. Intensity of inflammation was quantified, and cecal microbiota characterized by bacterial 16S ribosomal RNA (rRNA) amplicon sequencing.

Results

Daily oral administration of N ε-carboxymethyllysine did not induce intestinal inflammation and had limited impact on gut microbiota composition (Bacteroidaceae increase, Lachnospiraceae decrease). DSS and TNBS administration resulted in expected moderate experimental colitis with a shift of Bacteroidetes/Firmicutes ratio and a significant Proteobacteria increase but with distinct profiles: different Proteobacteria taxa for DSS, but mainly Enterobacteriaceae for TNBS. While N ε-carboxymethyllysine exposure failed to prevent the inflammatory response, it allowed maintenance of healthy gut microbiota profiles in mice treated with DSS (but not TNBS).

Conclusions

Repeated oral exposure to CML limits dysbiosis in experimental colitis. IBD patients may modulate their microbiota profile by regulating the level and type of dietary MRP consumption.
Literature
1.
Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13:701–712.CrossRefPubMed
2.
Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27:73–83.CrossRefPubMed
3.
Flint HJ, Scott KP, Louis P, Duncan SH. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol. 2012;9:577–589.CrossRefPubMed
4.
5.
6.
7.
Gomez A, Petrzelkova KJ, Burns MB, et al. Gut microbiome of coexisting BaAka pygmies and bantu reflects gradients of traditional subsistence patterns. Cell Rep. 2016;14:2142–2153.CrossRefPubMed
8.
Shen W, Wolf PG, Carbonero F, et al. Intestinal and systemic inflammatory responses are positively associated with sulfidogenic bacteria abundance in high-fat-fed male C57BL/6J mice. J Nutr. 2014;144:1181–1187. doi:10.​3945/​jn.​114.​194332.CrossRefPubMed
9.
Devkota S, Wang Y, Musch MW, et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10–/– mice. Nature. 2012;487:104–108.PubMedPubMedCentral
10.
He Q, Li X, Liu C, et al. Dysbiosis of the fecal microbiota in the TNBS-induced Crohn’s disease mouse model. Appl Microbiol Biotechnol. 2016;100:4485–4494.CrossRefPubMed
11.
12.
Munyaka PM, Rabbi MF, Khafipour E, Ghia J. Acute dextran sulfate sodium (DSS)-induced colitis promotes gut microbial dysbiosis in mice. J Basic Microbiol. 2016;56:986–998.CrossRefPubMed
13.
14.
15.
de Oliveira FC, Coimbra JSR, de Oliveira EB, Zuñiga ADG, Rojas EEG. Food protein–polysaccharide conjugates obtained via the Maillard reaction: a review. Crit Rev Food Sci Nutr. 2016;56:1108–1125.CrossRefPubMed
16.
Goldberg T, Cai W, Peppa M, et al. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc. 2004;104:1287–1291.CrossRefPubMed
17.
Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. The advanced glycation end product, nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem. 1996;271:9982–9986.CrossRefPubMed
18.
Macías-Cervantes MH, Rodríguez-Soto JMD, Uribarri J, Díaz-Cisneros FJ, Cai W, Garay-Sevilla ME. Effect of an advanced glycation end product-restricted diet and exercise on metabolic parameters in adult overweight men. Nutrition. 2015;31:446–451.CrossRefPubMed
19.
Roncero-Ramos I, Delgado-Andrade C, Tessier FJ, et al. Metabolic transit of n ε-carboxymethyl-lysine after consumption of AGEs from bread crust. Food Funct. 2013;4:1032–1039.CrossRefPubMed
20.
21.
Jara N, Leal M, Bunout D, et al. Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic patients. Nutr Hosp. 2012;27:1272–1278.PubMed
22.
Llaurado G, Ceperuelo-Mallafre V, Vilardell C, et al. Advanced glycation end products are associated with arterial stiffness in type 1 diabetes. J Endocrinol. 2014;221:405–413. doi:10.​1530/​JOE-13-0407.CrossRefPubMed
23.
Mishra N, Saxena S, Shukla RK, et al. Association of serum N ε-carboxy methyl lysine with severity of diabetic retinopathy. J Diabetes Complicat. 2016;30:511–517.CrossRefPubMed
24.
Van Eupen MG, Schram MT, Colhoun HM, Scheijen JL, Stehouwer CD, Schalkwijk CG. Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification. Cardiovasc Diabetol. 2013;12:149.CrossRefPubMedPubMedCentral
25.
Dammann P, Sell DR, Begall S, Strauch C, Monnier VM. Advanced glycation end-products as markers of aging and longevity in the long-lived Ansell’s mole-rat (Fukomys anselli). J Gerontol Ser A Biomed Sci Med Sci. 2011;67:573–583.
26.
Van Puyvelde K, Mets T, Njemini R, Beyer I, Bautmans I. Effect of advanced glycation end product intake on inflammation and aging: a systematic review. Nutr Rev. 2014;72:638–650.CrossRefPubMed
27.
Whitson HE, Arnold AM, Yee LM, et al. Serum carboxymethyl-lysine, disability, and frailty in older persons: the cardiovascular health study. J Gerontol Ser A Biomed Sci Med Sci. 2013;69:710–716.CrossRef
28.
Poulsen MW, Bak MJ, Andersen JM, et al. Effect of dietary advanced glycation end products on postprandial appetite, inflammation, and endothelial activation in healthy overweight individuals. Eur J Nutr. 2014;53:661–672.CrossRefPubMed
29.
30.
Gaens KH, Ferreira I, van de Waarenburg MP, et al. Protein-bound plasma nepsilon-(carboxymethyl)lysine is inversely associated with central obesity and inflammation and significantly explain a part of the central obesity-related increase in inflammation: the Hoorn and CODAM studies. Arterioscler Thromb Vasc Biol. 2015;35:2707–2713. doi:10.​1161/​ATVBAHA.​115.​306106.CrossRefPubMed
31.
Delgado-Andrade C. Carboxymethyl-lysine: thirty years of investigation in the field of AGE formation. Food Funct. 2016;7:46–57.CrossRefPubMed
32.
Tessier FJ, Niquet-Léridon C, Jacolot P, et al. Quantitative assessment of organ distribution of dietary protein-bound 13C-labeled nɛ-carboxymethyllysine after a chronic oral exposure in mice. Mol Nutr Food Res. 2016;60:2446–2456.CrossRefPubMed
33.
Tuohy KM, Hinton DJ, Davies SJ, Crabbe MJC, Gibson GR, Ames JM. Metabolism of Maillard reaction products by the human gut microbiota—implications for health. Mol Nutr Food Res. 2006;50:847–857.CrossRefPubMed
34.
Hellwig M, Bunzel D, Huch M, Franz CM, Kulling SE, Henle T. Stability of individual Maillard reaction products in the presence of the human colonic microbiota. J Agric Food Chem. 2015;63:6723–6730.CrossRefPubMed
35.
Helou C, Marier D, Jacolot P, et al. Microorganisms and Maillard reaction products: a review of the literature and recent findings. Amino Acids. 2014;46:267–277.CrossRefPubMed
36.
Helou C, Denis S, Spatz M, et al. Insights into bread melanoidins: fate in the upper digestive tract and impact on the gut microbiota using in vitro systems. Food Funct. 2015;6:3737–3745.CrossRefPubMed
37.
Seiquer I, Rubio LA, Peinado MJ, Delgado-Andrade C, Navarro MP. Maillard reaction products modulate gut microbiota composition in adolescents. Mol Nutr Food Res. 2014;58:1552–1560.CrossRefPubMed
38.
Anton PM, Craus A, Niquet-Léridon C, Tessier FJ. Highly heated food rich in Maillard reaction products limit an experimental colitis in mice. Food Funct. 2012;3:941–949.CrossRefPubMed
39.
Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96:795–803.CrossRefPubMed
40.
Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98:694–702.CrossRefPubMed
41.
Chassaing B, Aitken JD, Malleshappa M, Vijay‐Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014:15.25.1–15.25.14.
42.
43.
Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78:206–209.CrossRefPubMed
44.
45.
Kozich JJ, Westcott SL, Baxter NT, Highlander SK, Schloss PD. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol. 2013;79:5112–5120. doi:10.​1128/​AEM.​01043-13.CrossRefPubMedPubMedCentral
46.
Kuczynski J, Stombaugh J, Walters WA, González A, Caporaso JG, Knight R. Using QIIME to analyze 16S rRNA gene sequences from microbial communities. Curr Protoc Microbiol. 2012;Chapter 1:Unit 1E.5.PubMed
47.
Henle T. Dietary advanced glycation end products—a risk to human health? A call for an interdisciplinary debate. Mol Nutr Food Res. 2007;51:1075–1078.CrossRefPubMed
48.
Thornalley PJ. Dietary AGEs and ALEs and risk to human health by their interaction with the receptor for advanced glycation endproducts (RAGE)—an introduction. Mol Nutr Food Res. 2007;51:1107–1110.CrossRefPubMed
49.
Angoorani P, Ejtahed H, Mirmiran P, Mirzaei S, Azizi F. Dietary consumption of advanced glycation end products and risk of metabolic syndrome. Int J Food Sci Nutr. 2016;67:170–176.CrossRefPubMed
50.
Davis KE, Prasad C, Vijayagopal P, Juma S, Imrhan V. Advanced glycation end products, inflammation, and chronic metabolic diseases: links in a chain? Crit Rev Food Sci Nutr. 2016;56:989–998.CrossRefPubMed
51.
Ames JM. Evidence against dietary advanced glycation endproducts being a risk to human health. Mol Nutr Food Res. 2007;51:1085–1090.CrossRefPubMed
52.
Šebeková K, Somoza V. Dietary advanced glycation endproducts (AGEs) and their health effects—PRO. Mol Nutr Food Res. 2007;51:1079–1084.CrossRefPubMed
53.
Li M, Zeng M, He Z, et al. Effects of long-term exposure to free N ε-(carboxymethyl) lysine on rats fed a high-fat diet. J Agric Food Chem. 2015;63:10995–11001.CrossRefPubMed
54.
Hernandez-Hernandez O, Sanz ML, Kolida S, Rastall RA, Moreno FJ. In vitro fermentation by human gut bacteria of proteolytically digested caseinomacropeptide nonenzymatically glycosylated with prebiotic carbohydrates. J Agric Food Chem. 2011;59:11949–11955.CrossRefPubMed
55.
Reichardt N, Gniechwitz D, Steinhart H, Bunzel M, Blaut M. Characterization of high molecular weight coffee fractions and their fermentation by human intestinal microbiota. Mol Nutr Food Res. 2009;53:287–299.CrossRefPubMed
56.
Borrelli RC, Fogliano V. Bread crust melanoidins as potential prebiotic ingredients. Mol Nutr Food Res. 2005;49:673–678.CrossRefPubMed
57.
Carbonero F, Benefiel AC, Gaskins HR. Contributions of the microbial hydrogen economy to colonic homeostasis. Nat Rev Gastroenterol Hepatol. 2012;9:504–518.CrossRefPubMed
58.
59.
Kang S, Denman SE, Morrison M, et al. Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray. Inflamm Bowel Dis. 2010;16:2034–2042.CrossRefPubMed
60.
Williams KL, Fuller CR, Dieleman LA, et al. Enhanced survival and mucosal repair after dextran sodium sulfate-induced colitis in transgenic mice that overexpress growth hormone. Gastroenterology. 2001;120:925–937.CrossRefPubMed
61.
Jurjus AR, Khoury NN, Reimund J. Animal models of inflammatory bowel disease. J Pharmacol Toxicol Methods. 2004;50:81–92.CrossRefPubMed
62.
Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med. 1995;182:1281–1290.CrossRefPubMed
63.
64.
Mills D, Tuohy K, Booth J, et al. Dietary glycated protein modulates the colonic microbiota towards a more detrimental composition in ulcerative colitis patients and non-ulcerative colitis subjects. J Appl Microbiol. 2008;105:706–714.CrossRefPubMed
65.
Konikoff T, Gophna U. Oscillospira: a central, enigmatic component of the human gut microbiota. Trends Microbiol. 2016;24:523–524.CrossRefPubMed
Metadata
Title
Repeated Oral Exposure to N ε-Carboxymethyllysine, a Maillard Reaction Product, Alleviates Gut Microbiota Dysbiosis in Colitic Mice
Authors
Nesreen ALJahdali
Pascale Gadonna-Widehem
Carine Delayre-Orthez
David Marier
Benjamin Garnier
Franck Carbonero
Pauline M. Anton
Publication date
01-12-2017
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 12/2017
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4767-8

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