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Dr. Pauline ANTON
Transformations et Agro-Ressources, Institut Polytechnique UniLaSalle, Université d’Artois, URL-7519, France

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Research Keywords & Expertise

0 Human Nutrition
0 Developmental Origins of Health and Diseases
0 Gut–brain–microbiota axis
0 Immuno-endocrine gut homeostasis settlement
0 Toxic residues in food

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Journal article
Published: 09 June 2021 in Toxics
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Pesticide residues represent an important category of food contaminants. Furthermore, during food processing, some advanced glycation end-products resulting from the Maillard reaction can be formed. They may have adverse health effects, in particular on the digestive tract function, alone and combined. We sought to validate an in vitro model of the human intestinal barrier to mimic the effects of these food contaminants on the epithelium. A co-culture of Caco-2/TC7 cells and HT29-MTX was stimulated for 6 h with chlorpyrifos (300 μM), acrylamide (5 mM), Nε-Carboxymethyllysine (300 μM) alone or in cocktail with a mix of pro-inflammatory cytokines. The effects of those contaminants on the integrity of the gut barrier and the inflammatory response were analyzed. Since the co-culture responded to inflammatory stimulation, we investigated whether this model could be used to evaluate the effects of food contaminants on the human intestinal epithelium. CPF alone affected tight junctions’ gene expression, without inducing any inflammation or alteration of intestinal permeability. CML and acrylamide decreased mucins gene expression in the intestinal mucosa, but did not affect paracellular intestinal permeability. CML exposure activated the gene expression of MAPK pathways. The co-culture response was stable over time. This cocktail of food contaminants may thus alter the gut barrier function.

ACS Style

Marion Guibourdenche; Johanna Haug; Noëllie Chevalier; Madeleine Spatz; Nicolas Barbezier; Jérôme Gay-Quéheillard; Pauline Anton. Food Contaminants Effects on an In Vitro Model of Human Intestinal Epithelium. Toxics 2021, 9, 135 .

AMA Style

Marion Guibourdenche, Johanna Haug, Noëllie Chevalier, Madeleine Spatz, Nicolas Barbezier, Jérôme Gay-Quéheillard, Pauline Anton. Food Contaminants Effects on an In Vitro Model of Human Intestinal Epithelium. Toxics. 2021; 9 (6):135.

Chicago/Turabian Style

Marion Guibourdenche; Johanna Haug; Noëllie Chevalier; Madeleine Spatz; Nicolas Barbezier; Jérôme Gay-Quéheillard; Pauline Anton. 2021. "Food Contaminants Effects on an In Vitro Model of Human Intestinal Epithelium." Toxics 9, no. 6: 135.

Review
Published: 21 June 2020 in World Journal of Gastroenterology
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Early childhood growth and development is conditioned by the consecutive events belonging to perinatal programming. This critical window of life will be very sensitive to any event altering programming of the main body functions. Programming of gut function, which is starting right after conception, relates to a very well-established series of cellular and molecular events associating all types of cells present in this organ, including neurons, endocrine and immune cells. At birth, this machinery continues to settle with the establishment of extra connection between enteric and other systemic systems and is partially under the control of gut microbiota activity, itself being under the densification and the diversification of microorganisms’ population. As thus, any environmental factor interfering on this pre-established program may have a strong incidence on body functions. For all these reasons, pregnant women, fetuses and infants will be particularly susceptible to environmental factors and especially food contaminants. In this review, we will summarize the actual understanding of the consequences of repeated low-level exposure to major food contaminants on gut homeostasis settlement and on brain/gut axis communication considering the pivotal role played by the gut microbiota during the fetal and postnatal stages and the presumed consequences of these food toxicants on the individuals especially in relation with the risks of developing later in life non-communicable chronic diseases.

ACS Style

Elodie Sarron; Maxime Pérot; Nicolas Barbezier; Carine Delayre-Orthez; Jérôme Gay-Quéheillard; Pauline M Anton. Early exposure to food contaminants reshapes maturation of the human brain-gut-microbiota axis. World Journal of Gastroenterology 2020, 26, 3145 -3169.

AMA Style

Elodie Sarron, Maxime Pérot, Nicolas Barbezier, Carine Delayre-Orthez, Jérôme Gay-Quéheillard, Pauline M Anton. Early exposure to food contaminants reshapes maturation of the human brain-gut-microbiota axis. World Journal of Gastroenterology. 2020; 26 (23):3145-3169.

Chicago/Turabian Style

Elodie Sarron; Maxime Pérot; Nicolas Barbezier; Carine Delayre-Orthez; Jérôme Gay-Quéheillard; Pauline M Anton. 2020. "Early exposure to food contaminants reshapes maturation of the human brain-gut-microbiota axis." World Journal of Gastroenterology 26, no. 23: 3145-3169.

Journal article
Published: 17 January 2020 in Nutrients
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Melanoidins are the final Maillard reaction products (protein–carbohydrate complexes) produced in food by prolonged and intense heating. We assessed the impact of the consumption of melanoidins from barley malts on gut microbiota. Seventy-five mice were assigned into five groups, where the control group consumed a non-melanoidin malt diet, and other groups received melanoidin-rich malts in increments of 25% up to 100% melanoidin malts. Feces were sampled at days 0, 1, 2, 3, 7, 14, and 21 and the microbiota was determined using V4 bacterial 16S rRNA amplicon sequencing and short-chain fatty acids (SCFA) by gas chromatography. Increased melanoidins was found to result in significantly divergent gut microbiota profiles and supported sustained SCFA production. The relative abundance of Dorea, Oscillibacter, and Alisitpes were decreased, while Lactobacillus, Parasutterella, Akkermansia, Bifidobacterium, and Barnesiella increased. Bifidobacterium spp. and Akkermansia spp. were significantly increased in mice consuming the highest melanoidin amounts, suggesting remarkable prebiotic potential.

ACS Style

Nesreen Aljahdali; Pascale Gadonna-Widehem; Pauline M. Anton; Franck Carbonero. Gut Microbiota Modulation by Dietary Barley Malt Melanoidins. Nutrients 2020, 12, 241 .

AMA Style

Nesreen Aljahdali, Pascale Gadonna-Widehem, Pauline M. Anton, Franck Carbonero. Gut Microbiota Modulation by Dietary Barley Malt Melanoidins. Nutrients. 2020; 12 (1):241.

Chicago/Turabian Style

Nesreen Aljahdali; Pascale Gadonna-Widehem; Pauline M. Anton; Franck Carbonero. 2020. "Gut Microbiota Modulation by Dietary Barley Malt Melanoidins." Nutrients 12, no. 1: 241.

Journal article
Published: 31 July 2019 in Nutrients
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Iron is an essential nutrient needed for physiological functions, particularly during the developmental period of the early childhood of at-risk populations. The purpose of this study was to investigate, in an experimental colitis, the consequences of daily oral iron ingestion in the early period on the inflammatory response, the spleen T helper (Th) profiles and the associated molecular mechanisms. Juvenile mice orally received microencapsulated ferric iron or water for 6 weeks. On adult mice, we induced a sham or experimental trinitrobenzene sulfonic acid (TNBS) moderate colitis during the last week of the experiment before sacrificing the animals 7 days later. The severity of the gut inflammation was assessed by macroscopic damage scores (MDS) and the myeloperoxidase activity (MPO). Th profiles were evaluated by the examination of the splenic gene expression of key transcription factors of the Th differentiation (Tbet, Gata3, Foxp3 and RORγ) and the methylation of their respective promoter. While TNBS-induced colitis was associated with a change of the Th profile (notably an increase in the Tbet/Gata3 ratio in the spleen), the colitis-inhibition induced by ferric iron was associated with a limitation of the splenic Th profiles perturbation. The inhibition of the splenic Tbet gene overexpression was associated with an inhibition of promoter hypomethylation. In summary, mice treated by long-term oral ferric iron in the early period of life exhibited an inhibition of colitis associated with the inhibition of the splenic Tbet promoter hypomethylation and gene overexpression.

ACS Style

Chourouk Ettreiki; Abalo Chango; Nicolas Barbezier; Moise Coeffier; Pauline M Anton; Carine Delayre-Orthez. Prevention of Adult Colitis by Oral Ferric Iron in Juvenile Mice Is Associated with the Inhibition of the Tbet Promoter Hypomethylation and Gene Overexpression. Nutrients 2019, 11, 1758 .

AMA Style

Chourouk Ettreiki, Abalo Chango, Nicolas Barbezier, Moise Coeffier, Pauline M Anton, Carine Delayre-Orthez. Prevention of Adult Colitis by Oral Ferric Iron in Juvenile Mice Is Associated with the Inhibition of the Tbet Promoter Hypomethylation and Gene Overexpression. Nutrients. 2019; 11 (8):1758.

Chicago/Turabian Style

Chourouk Ettreiki; Abalo Chango; Nicolas Barbezier; Moise Coeffier; Pauline M Anton; Carine Delayre-Orthez. 2019. "Prevention of Adult Colitis by Oral Ferric Iron in Juvenile Mice Is Associated with the Inhibition of the Tbet Promoter Hypomethylation and Gene Overexpression." Nutrients 11, no. 8: 1758.

Journal article
Published: 01 December 2017 in Nutrition Research
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Links between food and inflammatory bowel diseases (IBDs) are often suggested, but the role of food processing has not been extensively studied. Heat treatment is known to cause the loss of nutrients and the appearance of neoformed compounds such as Maillard reaction products. Their involvement in gut inflammation is equivocal, as some may have proinflammatory effects, whereas other seem to be protective. As IBDs are associated with the recruitment of immune cells, including mast cells, we raised the hypothesis that dietary Maillard reaction products generated through heat treatment of food may limit the colitic response and its associated recruitment of mast cells. An experimental model of colitis was used in mice submitted to mildly and highly heated rodent food. Adult male mice were divided in 3 groups and received nonheated, mildly heated, or highly heated chow during 21 days. In the last week of the study, each group was split into 2 subgroups, submitted or not (controls) to dextran sulfate sodium (DSS) colitis. Weight variations, macroscopic lesions, colonic myeloperoxidase activity, and mucosal mast cell number were evaluated at the end of the experiment. Only highly heated chow significantly prevented DSS-induced weight loss, myeloperoxidase activity, and mast cell number increase in the colonic mucosa of DSS-colitic mice. We suggest that Maillard reaction products from highly heated food may limit the occurrence of inflammatory phases in IBD patients.

ACS Style

Issam Al Amir; David Dubayle; Anne Héron; Carine Delayre-Orthez; Pauline M. Anton. Maillard reaction products from highly heated food prevent mast cell number increase and inflammation in a mouse model of colitis. Nutrition Research 2017, 48, 26 -32.

AMA Style

Issam Al Amir, David Dubayle, Anne Héron, Carine Delayre-Orthez, Pauline M. Anton. Maillard reaction products from highly heated food prevent mast cell number increase and inflammation in a mouse model of colitis. Nutrition Research. 2017; 48 ():26-32.

Chicago/Turabian Style

Issam Al Amir; David Dubayle; Anne Héron; Carine Delayre-Orthez; Pauline M. Anton. 2017. "Maillard reaction products from highly heated food prevent mast cell number increase and inflammation in a mouse model of colitis." Nutrition Research 48, no. : 26-32.

Original article
Published: 30 September 2017 in Digestive Diseases and Sciences
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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. The aim of this study is to determine the effect of repeated oral ingestion of Nε-carboxymethyllysine (CML), an advanced MRP, on the onset of two models of experimental IBD and on the gut microbiota composition of mice. Mice received either saline (control) or Nε-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. Daily oral administration of Nε-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 Nε-carboxymethyllysine exposure failed to prevent the inflammatory response, it allowed maintenance of healthy gut microbiota profiles in mice treated with DSS (but not TNBS). 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.

ACS Style

Nesreen Aljahdali; Pascale Gadonna-Widehem; Carine Delayre-Orthez; David Marier; Benjamin Garnier; Franck Carbonero; Pauline M. Anton. Repeated Oral Exposure to N ε-Carboxymethyllysine, a Maillard Reaction Product, Alleviates Gut Microbiota Dysbiosis in Colitic Mice. Digestive Diseases and Sciences 2017, 62, 3370 -3384.

AMA Style

Nesreen Aljahdali, Pascale Gadonna-Widehem, Carine Delayre-Orthez, David Marier, Benjamin Garnier, Franck Carbonero, Pauline M. Anton. Repeated Oral Exposure to N ε-Carboxymethyllysine, a Maillard Reaction Product, Alleviates Gut Microbiota Dysbiosis in Colitic Mice. Digestive Diseases and Sciences. 2017; 62 (12):3370-3384.

Chicago/Turabian Style

Nesreen Aljahdali; Pascale Gadonna-Widehem; Carine Delayre-Orthez; David Marier; Benjamin Garnier; Franck Carbonero; Pauline M. Anton. 2017. "Repeated Oral Exposure to N ε-Carboxymethyllysine, a Maillard Reaction Product, Alleviates Gut Microbiota Dysbiosis in Colitic Mice." Digestive Diseases and Sciences 62, no. 12: 3370-3384.

Journals
Published: 28 June 2017 in Food & Function
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A comparison between the impacts of advanced (Nε-carboxymethyllysine – CML) and terminal (melanoidins) Maillard reaction products from bread on gut microbiota was carried out in this study.

ACS Style

C. Helou; P. M. Anton; C. Niquet-Léridon; M. Spatz; F. J. Tessier; P. Gadonna-Widehem. Fecal excretion of Maillard reaction products and the gut microbiota composition of rats fed with bread crust or bread crumb. Food & Function 2017, 8, 2722 -2730.

AMA Style

C. Helou, P. M. Anton, C. Niquet-Léridon, M. Spatz, F. J. Tessier, P. Gadonna-Widehem. Fecal excretion of Maillard reaction products and the gut microbiota composition of rats fed with bread crust or bread crumb. Food & Function. 2017; 8 (8):2722-2730.

Chicago/Turabian Style

C. Helou; P. M. Anton; C. Niquet-Léridon; M. Spatz; F. J. Tessier; P. Gadonna-Widehem. 2017. "Fecal excretion of Maillard reaction products and the gut microbiota composition of rats fed with bread crust or bread crumb." Food & Function 8, no. 8: 2722-2730.

Journal article
Published: 01 May 2015 in European Journal of Pharmaceutical Sciences
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Reducing the differentiation period for obtaining an in vitro intestinal barrier model is required to reduce the duration and cost for drug screening assays. In this frame, the Caco-2/TC7 subclone differentiation state was investigated from day 0 (D0) to day 32 (D32). As such, the expression of 45 genes (including cell junction, cell polarization, cell functionality, drug transport and metabolism genes) was followed throughout the 32 days. In parallel, the monolayer polarization and the formation of the cellular junctions were characterized by the immuno-staining of occludin, claudin-1 and actin proteins. The cell monolayer permeability was analyzed via transepithelial electric resistance measurements and paracellular transport of Lucifer Yellow. The P-gp efflux efficiency was assessed by rhodamine 123 transport. Alkaline phosphate activity was quantified to assess the cell differentiation. Three stages of differentiation were observed using the clustering of principal component analysis of the RTqPCR data and the overall assays. From D0 to D10, cells were in a proliferation stage and under-differentiated; from D14 to D21 a stable differentiation stage was reached; from D25 to D32 the epithelium seemed to enter into a post-differentiated stage. This study demonstrates that Caco-2/TC7 cells are functional and ready for use in drug screening permeability assays from 14 days in culture when compared with conventional 21 days for Caco-2 cells. In addition, this study provides a refined set of data allowing temporal and multi scale investigations, due to the intracellular kinetics and mRNA levels that can be correlated with membrane protein kinetics and functional extracellular activities. Therefore, shorter time in culture combined with a better knowledge of the cells during the time in culture will in turn help to improve the quality and cost of Caco-2/TC7 assays for drug development.

ACS Style

Perrine Zeller; Thibault Bricks; Guillaume Vidal; Sébastien Jacques; Pauline Anton; Eric Leclerc. Multiparametric temporal analysis of the Caco-2/TC7 demonstrated functional and differentiated monolayers as early as 14 days of culture. European Journal of Pharmaceutical Sciences 2015, 72, 1 -11.

AMA Style

Perrine Zeller, Thibault Bricks, Guillaume Vidal, Sébastien Jacques, Pauline Anton, Eric Leclerc. Multiparametric temporal analysis of the Caco-2/TC7 demonstrated functional and differentiated monolayers as early as 14 days of culture. European Journal of Pharmaceutical Sciences. 2015; 72 ():1-11.

Chicago/Turabian Style

Perrine Zeller; Thibault Bricks; Guillaume Vidal; Sébastien Jacques; Pauline Anton; Eric Leclerc. 2015. "Multiparametric temporal analysis of the Caco-2/TC7 demonstrated functional and differentiated monolayers as early as 14 days of culture." European Journal of Pharmaceutical Sciences 72, no. : 1-11.

Journal article
Published: 01 August 2014 in Toxicology in Vitro
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We developed a new biological model to mimic the organ-organ interactions between the intestine and the liver. We coupled polycarbonate cell culture inserts and microfluidic biochips in an integrated fluidic platform allowing dynamic co-cultures (called IIDMP for Integrated Insert in a Dynamic Microfluidic Platform). The intestinal compartment was simulated using Caco-2 TC7 cells and the liver one by HepG2 C3A. We showed that Caco-2 TC7 viability, barrier integrity and functionality (assessed by paracellular and active transport), were not altered during co-cultures in the bioreactor in comparison with the conventional insert Petri cultures. In parallel, the viability and metabolism of the HepG2 C3A cells were maintained in the microfluidic biochips. Then, as proof of concept, we used the bioreactor to follow the transport of phenacetin through the intestinal barrier and its metabolism into paracetamol by the CYP1A of the HepG2 C3A cells. Our results demonstrated the performance of this bioreactor with cell co-cultures compared to static co-culture controls in which weak biotransformation into paracetamol was detected. Our study illustrated the interest of such a bioreactor combining the advantages of a cell culture barrier and of liver microfluidic cultures in a common framework for in vitro studies.

ACS Style

Thibault Bricks; Patrick Paullier; Audrey Legendre; Marie-José Fleury; Perrine Zeller; Franck Merlier; Pauline Anton; Eric Leclerc. Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines. Toxicology in Vitro 2014, 28, 885 -895.

AMA Style

Thibault Bricks, Patrick Paullier, Audrey Legendre, Marie-José Fleury, Perrine Zeller, Franck Merlier, Pauline Anton, Eric Leclerc. Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines. Toxicology in Vitro. 2014; 28 (5):885-895.

Chicago/Turabian Style

Thibault Bricks; Patrick Paullier; Audrey Legendre; Marie-José Fleury; Perrine Zeller; Franck Merlier; Pauline Anton; Eric Leclerc. 2014. "Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines." Toxicology in Vitro 28, no. 5: 885-895.

Journal article
Published: 16 November 2012 in Amino Acids
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Milk proteins are frequently used as supplements in fortified foods. However, processing produces chemical changes which likely affect the nutritional advantage. This study was intended to explore the possible difference in digestibility between extruded and non-extruded caseins and how the dietary N ε -carboxymethyllysine (CML) is metabolised. Normal rats were randomized into either an extruded protein diet (EP) or the same with unextruded proteins (UEP), for two periods of 2 weeks at 7 to 9 and 11 to 13 weeks of age. However, no difference in protein digestibility was detected between the two diets, either in young or in adult animals, despite a 9.4-fold higher level of CML and an 8.5-fold higher level of lysinoalanine in the EP than in the UEP. No diet-related changes were observed in plasma CML, either protein bound or free. Amounts of 38 and 48 % of the orally absorbed CML were excreted in urine and faeces, respectively, in UEP-fed rats. Lower rates of excretion were found in the EP-fed rats (23 and 37 %, respectively). A second animal study using a single oral dose of free CML (400 μg/rat) was set up to measure the systemic concentration of CML every hour from 0 to 4 h. It revealed that protein-bound CML was not affected by the oral dose of CML, and the highest free CML level found in the circulation was 600 ng/mL. Extruded proteins, therefore, appear to be well digested, and CML rapidly eliminated. Since its elimination is, however, incomplete, the question of its biodistribution and metabolism remains open.

ACS Style

Issam Alamir; Céline Niquet-Leridon; Philippe Jacolot; Camille Rodriguez; Martine Orosco; Pauline Anton; Frédéric J. Tessier. Digestibility of extruded proteins and metabolic transit of N ε -carboxymethyllysine in rats. Amino Acids 2012, 44, 1441 -1449.

AMA Style

Issam Alamir, Céline Niquet-Leridon, Philippe Jacolot, Camille Rodriguez, Martine Orosco, Pauline Anton, Frédéric J. Tessier. Digestibility of extruded proteins and metabolic transit of N ε -carboxymethyllysine in rats. Amino Acids. 2012; 44 (6):1441-1449.

Chicago/Turabian Style

Issam Alamir; Céline Niquet-Leridon; Philippe Jacolot; Camille Rodriguez; Martine Orosco; Pauline Anton; Frédéric J. Tessier. 2012. "Digestibility of extruded proteins and metabolic transit of N ε -carboxymethyllysine in rats." Amino Acids 44, no. 6: 1441-1449.

Journals
Published: 01 January 2012 in Food & Function
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Maillard reaction products (MRPs) are a mixture of compounds generated after the heat treatment of food. High circulating levels of MRPs have been associated with degenerative pathologies such as diabetes, but little is known about their effect on the gut, the main organ in contact with food-derived MRPs. This study was aimed at determining whether repeated low-level exposure to MRPs, generated via two different heat treatments, can contribute to the modulation of experimental colitis in mice. In the first series of experiments, we tested whether pellets rich in MRPs would increase plasmatic and faecal concentration of MRPs. In the second series, we assessed whether two levels of pellet-derived MRPs would be able to modulate chemically-induced inflammation and affect tissue healing. The ingestion of MRPs correlates with the increase of its plasmatic and faecal concentration. Highly treated pellets were proved to significantly protect against inflammation whereas standard or moderately heated pellets had no effect on the inflammatory course. The chemical analysis of the different pellets indicated that high heating generates more melanoidins. There is a correlation between the exposure to highly heated foods and the reduction of murine inflammation, of which the mechanisms remain to be elucidated.

ACS Style

Pauline Anton; Alexandre Craus; Céline Niquet-Léridon; Frederic Tessier. Highly heated food rich in Maillard reaction products limit an experimental colitis in mice. Food & Function 2012, 3, 941 -949.

AMA Style

Pauline Anton, Alexandre Craus, Céline Niquet-Léridon, Frederic Tessier. Highly heated food rich in Maillard reaction products limit an experimental colitis in mice. Food & Function. 2012; 3 (9):941-949.

Chicago/Turabian Style

Pauline Anton; Alexandre Craus; Céline Niquet-Léridon; Frederic Tessier. 2012. "Highly heated food rich in Maillard reaction products limit an experimental colitis in mice." Food & Function 3, no. 9: 941-949.

Journal article
Published: 30 April 2009 in The Journal of Nutritional Biochemistry
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International audienceThe integrated view of the expression of genes involved in folate-dependent one-carbon metabolism (FOCM) under folate deficiency remains unknown. Dynamics of changes in the transcriptional expression of 28 genes involved in the FOCM network were evaluated at different time points (0, 2, 4, 6, 12, 24 and 48 h) in human hepatoma HepG2 cell line. Combined experimental and computational approaches were conducted for emphasizing characteristic patterns in the gene expression changes produced by cellular folate deficiency. Bivariate analysis showed that folate deficiency (0.3 nmol/L of folate vs. 2.27 mumol/L in control medium) displayed rapid and coordinated regulation during the first 2 h with differential expression for hRfc1 (increased by 69%) and Ahcy (decreased by 437%). Density analysis through the time points gave evidence of differential expression for five genes (Ahcy, Cth, Gnmt, Mat1A, Mtrr and hRfc1). Differential expression of Ahcy, Gnmt, Mat1A and Mtrr was confirmed by time-series analysis gene expression. We also found a marked differential expression of Mtrr. Qualitative analysis of genes allowed identifying four clusters of gene that was coexpressed. Two of these clusters were consistent with specific metabolic functions as they associated genes involved in the remethylation (Mthfr and Mtrr) and in the transmethylation (Dnmt1and Dnmt3B) pathways. The study shows a strong influence of folate status on Mtrr transcription in HepG2 cells. It suggests also that folate deficiency produces transcription changes that particularly involve the clusters of genes related with the remethylation and the transmethylation pathways

ACS Style

Abalo Chango; Afif Abdel Nour; Souad Bousserouel; Damien Eveillard; Pauline M. Anton; Jean-Louis Guéant. Time course gene expression in the one-carbon metabolism network using HepG2 cell line grown in folate-deficient medium. The Journal of Nutritional Biochemistry 2009, 20, 312 -320.

AMA Style

Abalo Chango, Afif Abdel Nour, Souad Bousserouel, Damien Eveillard, Pauline M. Anton, Jean-Louis Guéant. Time course gene expression in the one-carbon metabolism network using HepG2 cell line grown in folate-deficient medium. The Journal of Nutritional Biochemistry. 2009; 20 (4):312-320.

Chicago/Turabian Style

Abalo Chango; Afif Abdel Nour; Souad Bousserouel; Damien Eveillard; Pauline M. Anton; Jean-Louis Guéant. 2009. "Time course gene expression in the one-carbon metabolism network using HepG2 cell line grown in folate-deficient medium." The Journal of Nutritional Biochemistry 20, no. 4: 312-320.

Journal article
Published: 01 November 2008 in American Journal of Physiology-Endocrinology and Metabolism
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Low birth weight resulting from intrauterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low-birth-weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that 1) IUGR piglets present altered postnatal growth and increased adiposity; 2) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behavior; and 3) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition, and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the IUGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR.

ACS Style

L. Attig; J. Djiane; A. Gertler; O. Rampin; Thibaut Larcher; S. Boukthir; P. M. Anton; J. Y. Madec; I. Gourdou; L. Abdennebi-Najar. Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development. American Journal of Physiology-Endocrinology and Metabolism 2008, 295, E1117 -E1125.

AMA Style

L. Attig, J. Djiane, A. Gertler, O. Rampin, Thibaut Larcher, S. Boukthir, P. M. Anton, J. Y. Madec, I. Gourdou, L. Abdennebi-Najar. Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development. American Journal of Physiology-Endocrinology and Metabolism. 2008; 295 (5):E1117-E1125.

Chicago/Turabian Style

L. Attig; J. Djiane; A. Gertler; O. Rampin; Thibaut Larcher; S. Boukthir; P. M. Anton; J. Y. Madec; I. Gourdou; L. Abdennebi-Najar. 2008. "Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development." American Journal of Physiology-Endocrinology and Metabolism 295, no. 5: E1117-E1125.

Journal article
Published: 05 April 2007 in Gut
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Urocortin II (UcnII) is a neuropeptide that binds with high affinity to the corticotropin-releasing hormone receptor 2 (CRHR2) in peripheral tissues. UcnII is synthesised in the intestine, but its role in human intestinal inflammation is largely unknown. Responses of human colonic epithelial cells expressing CRHR2 to stimulation by UcnII were measured using ELISA, western blot analysis, real-time reverse transcription-PCR (RT-PCR) and interleukin (IL)8 promoter activity. Expression levels of CRHR2 and UcnII in human colitis were determined by immunofluorescence and real-time RT-PCR in mucosal biopsies from patients with Crohn's and ulcerative colitis, and in human intestinal xenografts after exposure to Clostridium difficile toxin A. It is reported here that expression of CRHR2 mRNA and protein in human colonic epithelial cells (HT-29) are increased by exposure to C difficile toxin A or tumour necrosis factor (TNF)alpha. Stimulation of non-transformed NCM460 colonocytes overexpressing CRHR2alpha receptor with UcnII resulted in a time- and concentration-dependent increase in IL8 production. UcnII stimulation also led to activation of nuclear factor-kappaB (NF-kappaB) and mitogen-acivated protein (MAP) kinase in these cells, as evidenced by degradation of IkappaBalpha and phosphorylation of the p65 subunit of NF-kappaB and extracellularly regulated kinase (ERK) 1/2. Furthermore, expression of UcnII and CRHR2 mRNA was increased in mucosal samples of patients with inflammatory bowel disease, and after exposure of human intestinal xenografts to C difficile toxin A. These results suggest that UcnII has pro-inflammatory effects in human intestinal cells via the CRHR2alpha receptor and may play an important role in the pathophysiology of colitis in humans.

ACS Style

Alan Moss; Pauline Anton; Tor Savidge; Paul Newman; Adam S Cheifetz; Jerome Gay; Sophia Paraschos; Michael Weinstein Winter; Mary P Moyer; Katia Karalis; Efi Kokkotou; Charalabos Pothoulakis. Urocortin II mediates pro-inflammatory effects in human colonocytes via corticotropin-releasing hormone receptor 2. Gut 2007, 56, 1210 -1217.

AMA Style

Alan Moss, Pauline Anton, Tor Savidge, Paul Newman, Adam S Cheifetz, Jerome Gay, Sophia Paraschos, Michael Weinstein Winter, Mary P Moyer, Katia Karalis, Efi Kokkotou, Charalabos Pothoulakis. Urocortin II mediates pro-inflammatory effects in human colonocytes via corticotropin-releasing hormone receptor 2. Gut. 2007; 56 (9):1210-1217.

Chicago/Turabian Style

Alan Moss; Pauline Anton; Tor Savidge; Paul Newman; Adam S Cheifetz; Jerome Gay; Sophia Paraschos; Michael Weinstein Winter; Mary P Moyer; Katia Karalis; Efi Kokkotou; Charalabos Pothoulakis. 2007. "Urocortin II mediates pro-inflammatory effects in human colonocytes via corticotropin-releasing hormone receptor 2." Gut 56, no. 9: 1210-1217.

Journal article
Published: 30 January 2007 in Proceedings of the National Academy of Sciences
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We examined the hypothesis that substance P (SP) and the neurokinin-1 receptor (NK-1R), both in vitro and in vivo, promote mucosal healing during recovery from colitis by stimulating antiapoptotic pathways in human colonic epithelial cells. For the in vitro experiments, human nontransformed NCM460 colonocytes stably transfected with NK-1R (NCM460-NK-1R cells) were exposed to SP, and cell viability assays, TUNEL assays, and Western blot analyses were used to detect apoptotic and antiapoptotic pathways. SP exposure of NCM460-NK-1R colonocytes stimulated phosphorylation of the antiapoptotic molecule Akt and inhibited tamoxifen-induced cell death and apoptosis evaluated by the cell viability assay and poly(ADP-ribose) polymerase cleavage, respectively. SP-induced phosphorylation of Akt and cleavage of poly(ADP-ribose) polymerase were inhibited by blockade of integrin αVβ3, Jak2, and activation of phosphatidylinositol 3-kinase. For the in vivo experiments, C57BL/6 mice, administered 5% dextran sulfate (DSS) dissolved in tap water for 5 days followed by a 5-day recovery period, were treated with the NK-1R antagonist CJ-12,255 or vehicle. Vehicle-treated mice showed increased colonic Akt phosphorylation and apoptosis compared with mice that received no DSS. In contrast, daily i.p. administration of CJ-12,255 for 5 days post-DSS suppressed Akt activation, exacerbated colitis, and enhanced apoptosis, and pharmacologic inhibition of Akt, either alone or together with CJ-12,255, produced a similar effect. Thus, SP, through NK-1R, possesses antiapoptotic effects in the colonic mucosa by activating Akt, which prevents apoptosis and mediates tissue recovery during colitis.

ACS Style

Hon-Wai Koon; Dezheng Zhao; Yanai Zhan; Mary P. Moyer; Charalabos Pothoulakis. Substance P mediates antiapoptotic responses in human colonocytes by Akt activation. Proceedings of the National Academy of Sciences 2007, 104, 2013 -2018.

AMA Style

Hon-Wai Koon, Dezheng Zhao, Yanai Zhan, Mary P. Moyer, Charalabos Pothoulakis. Substance P mediates antiapoptotic responses in human colonocytes by Akt activation. Proceedings of the National Academy of Sciences. 2007; 104 (6):2013-2018.

Chicago/Turabian Style

Hon-Wai Koon; Dezheng Zhao; Yanai Zhan; Mary P. Moyer; Charalabos Pothoulakis. 2007. "Substance P mediates antiapoptotic responses in human colonocytes by Akt activation." Proceedings of the National Academy of Sciences 104, no. 6: 2013-2018.

Review article
Published: 31 October 2006 in Peptides
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It is well established that interactions of neuropeptides with several cell types at various parts of the intestine are critically involved in intestinal pathophysiology. Among them, neurotensin has been identified as an important mediator in the development and progress of several gastrointestinal functions and disease conditions, exerting its effects by interacting with specific receptors that exert direct and indirect effects on nerves, epithelial cells, and cells of the immune and inflammatory systems. This review summarizes our recent understanding on the participation of neurotensin in the physiology and pathophysiology of the small and large intestine, and discusses various mechanisms that could be involved in these actions.

ACS Style

Dezheng Zhao; Charalabos Pothoulakis. Effects of NT on gastrointestinal motility and secretion, and role in intestinal inflammation. Peptides 2006, 27, 2434 -2444.

AMA Style

Dezheng Zhao, Charalabos Pothoulakis. Effects of NT on gastrointestinal motility and secretion, and role in intestinal inflammation. Peptides. 2006; 27 (10):2434-2444.

Chicago/Turabian Style

Dezheng Zhao; Charalabos Pothoulakis. 2006. "Effects of NT on gastrointestinal motility and secretion, and role in intestinal inflammation." Peptides 27, no. 10: 2434-2444.

Journal article
Published: 28 April 2006 in Biochemical and Biophysical Research Communications
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Saccharomyces boulardii (Sb) is a non-pathogenic yeast that ameliorates intestinal injury and inflammation caused by a wide variety of enteric pathogens. We hypothesized that Sb may exert its probiotic effects by modulation of host cell signaling and pro-inflammatory gene expression. Human HT-29 colonocytes and THP-1 monocytes were stimulated with IL-1β, TNFα or LPS in the presence or absence of Sb culture supernatant (SbS). IL-8 protein and mRNA levels were measured by ELISA and RT-PCR, respectively. The effect of SbS on IκBα degradation was studied by Western blotting and on NF-κB-DNA binding by EMSA. NF-κB-regulated gene expression was evaluated by transient transfection of THP-1 cells with a NF-κB-responsive luciferase reporter gene. SbS inhibited IL-8 protein production in IL-1β or TNFα stimulated HT-29 cells (by 75% and 85%, respectively; P < 0.001) and prevented IL-1β-induced up-regulation of IL-8 mRNA. SbS also inhibited IL-8 production, prevented IκBα degradation, and reduced both NF-κB-DNA binding and NF-κB reporter gene up-regulation in IL-1β or LPS-stimulated THP-1 cells. Purification and characterization studies indicate that the S. boulardii anti-inflammatory factor (SAIF) is small (<1 kDa), heat stable, and water soluble. The probiotic yeast Saccharomyces boulardii exerts an anti-inflammatory effect by producing a low molecular weight soluble factor that blocks NF-κB activation and NF-κB-mediated IL-8 gene expression in intestinal epithelial cells and monocytes. SAIF may mediate, at least in part, the beneficial effects of Saccharomyces boulardii in infectious and non-infectious human intestinal disease.

ACS Style

Stavros Sougioultzis; Simos Simeonidis; K. Ramakrishnan Bhaskar; Xinhua Chen; Pauline Anton; Sarah Keates; Charalabos Pothoulakis; Ciarán P. Kelly. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression. Biochemical and Biophysical Research Communications 2006, 343, 69 -76.

AMA Style

Stavros Sougioultzis, Simos Simeonidis, K. Ramakrishnan Bhaskar, Xinhua Chen, Pauline Anton, Sarah Keates, Charalabos Pothoulakis, Ciarán P. Kelly. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression. Biochemical and Biophysical Research Communications. 2006; 343 (1):69-76.

Chicago/Turabian Style

Stavros Sougioultzis; Simos Simeonidis; K. Ramakrishnan Bhaskar; Xinhua Chen; Pauline Anton; Sarah Keates; Charalabos Pothoulakis; Ciarán P. Kelly. 2006. "Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression." Biochemical and Biophysical Research Communications 343, no. 1: 69-76.

Journal article
Published: 01 December 2005 in American Journal of Physiology-Gastrointestinal and Liver Physiology
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Epithelial neutrophil-activating peptide-78 (ENA-78), a member of the CXC chemokine subfamily, is induced by inflammatory cytokines in human colonic enterocyte cell lines and increased in the colon of patients with inflammatory bowel disease (IBD). Lipopolysaccharide-induced CXC-chemokine (LIX) was recently identified as the murine homolog of ENA-78. Here we show that, similar to ENA-78, inflammatory cytokine stimulation of a murine colonic epithelial cell line, MODE-K, results in increased LIX expression. Consistent with the expression pattern of ENA-78 in IBD, LIX expression is significantly increased in mice with colitis induced by the ingestion of dextran sodium sulfate (DSS). Treating mice with antisense oligonucleotides to LIX via rectal enema delivery before DSS treatment results in colonic enterocyte uptake and a significant reduction in neutrophil infiltration and severity of colitis. These findings indicate that LIX plays an integral role in the pathogenesis of DSS-induced colitis. Similarly, enterocyte-derived CXC chemokines may play a key role in regulating neutrophil recruitment and intestinal injury in IBD. The intracolonic administration of ENA-78 antisense oligonucleotides may be effective in treating distal ulcerative colitis in humans.

ACS Style

John H. Kwon; Andrew C. Keates; Pauline M. Anton; Maria Botero; Jeffrey D. Goldsmith; Ciaran P. Kelly. Topical antisense oligonucleotide therapy against LIX, an enterocyte-expressed CXC chemokine, reduces murine colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology 2005, 289, G1075 -G1083.

AMA Style

John H. Kwon, Andrew C. Keates, Pauline M. Anton, Maria Botero, Jeffrey D. Goldsmith, Ciaran P. Kelly. Topical antisense oligonucleotide therapy against LIX, an enterocyte-expressed CXC chemokine, reduces murine colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2005; 289 (6):G1075-G1083.

Chicago/Turabian Style

John H. Kwon; Andrew C. Keates; Pauline M. Anton; Maria Botero; Jeffrey D. Goldsmith; Ciaran P. Kelly. 2005. "Topical antisense oligonucleotide therapy against LIX, an enterocyte-expressed CXC chemokine, reduces murine colitis." American Journal of Physiology-Gastrointestinal and Liver Physiology 289, no. 6: G1075-G1083.

Comparative study
Published: 01 October 2004 in Antimicrobial Agents and Chemotherapy
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Although vancomycin and metronidazole effectively treat Clostridium difficile -associated diarrhea and colitis (CDAD), their use is associated with a high incidence of relapsing C. difficile infection. Rifalazil is a new benzoxazinorifamycin that possesses activity against Mycobacterium tuberculosis and gram-positive bacteria. Here we compared rifalazil and vancomycin for effectiveness in preventing or treating clindamycin-induced cecitis in a hamster model of CDAD. Golden Syrian hamsters were injected subcutaneously with clindamycin phosphate (10 mg/kg), followed 24 h later by C. difficile gavage. Hamsters received by gavage for 5 days vehicle, vancomycin (50 mg/kg), or rifalazil (20 mg/kg) either simultaneously with (prophylactic protocol) or 24 h after C. difficile administration (treatment protocol). While all vehicle-administered animals became moribund within 48 h of C. difficile administration, no rifalazil- or vancomycin-treated animals in either protocol showed signs of morbidity after 7 days. Ceca of rifalazil-treated animals showed absence of epithelial cell damage, significantly reduced congestion and edema, and less, but not statistically significantly less, neutrophil infiltration compared to those of vehicle-treated animals. In contrast, vancomycin-treated animals demonstrated severe epithelial cell damage and mildly reduced congestion and edema. Moreover, hamsters relapsed and tested C. difficile toxin positive (by enzyme-linked immunosorbent assay) 10 to 15 days after discontinuation of vancomycin treatment. None of the rifalazil-treated hamsters showed signs of disease or presence of toxins in their feces 30 days after discontinuation of treatment. Our results indicate that once daily rifalazil may be superior to vancomycin for curative treatment of CDAD.

ACS Style

Pauline M. Anton; Michael J O'Brien; Efi Kokkotou; Barry Eisenstein; Arthur Michaelis; David Rothstein; Sophia Paraschos; Ciáran P. Kelly; Charalabos Pothoulakis. Rifalazil Treats and Prevents Relapse of Clostridium difficile -Associated Diarrhea in Hamsters. Antimicrobial Agents and Chemotherapy 2004, 48, 3975 -3979.

AMA Style

Pauline M. Anton, Michael J O'Brien, Efi Kokkotou, Barry Eisenstein, Arthur Michaelis, David Rothstein, Sophia Paraschos, Ciáran P. Kelly, Charalabos Pothoulakis. Rifalazil Treats and Prevents Relapse of Clostridium difficile -Associated Diarrhea in Hamsters. Antimicrobial Agents and Chemotherapy. 2004; 48 (10):3975-3979.

Chicago/Turabian Style

Pauline M. Anton; Michael J O'Brien; Efi Kokkotou; Barry Eisenstein; Arthur Michaelis; David Rothstein; Sophia Paraschos; Ciáran P. Kelly; Charalabos Pothoulakis. 2004. "Rifalazil Treats and Prevents Relapse of Clostridium difficile -Associated Diarrhea in Hamsters." Antimicrobial Agents and Chemotherapy 48, no. 10: 3975-3979.

Journal article
Published: 24 May 2004 in Proceedings of the National Academy of Sciences
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Clostridium difficile, the causative agent of antibiotic-associated colitis, mediates inflammatory diarrhea by releasing toxin A, a potent 308-kDa enterotoxin. Toxin A-induced inflammatory diarrhea involves many steps, including mucosal release of substance P (SP) corticotropin-releasing hormone (CRH) and neutrophil transmigration. Here we demonstrate that, compared with wild type, mice genetically deficient in CRH (Crh-/-) have dramatically reduced ileal fluid secretion, epithelial cell damage, and neutrophil transmigration 4 h after intraluminal toxin A administration. This response is associated with diminished mucosal activity of the neutrophil enzyme myeloperoxidase compared with that of wildtype mice. In wild-type mice, toxin A stimulates an increase in intestinal SP content compared with buffer administration. In contrast, toxin A administration in Crh-/- mice fails to result in an increased SP content. Moreover, immunohistochemical experiments showed that CRH and SP are colocalized in some enteric nerves of wild-type mice, and this colocalization is more evident after toxin A administration. These results provide direct evidence for a major proinflammatory role for CRH in the pathophysiology of enterotoxin-mediated inflammatory diarrhea and indicate a SP-linked pathway

ACS Style

Pauline Anton; J. Gay; A. Mykoniatis; A. Pan; Michael J O'Brien; D. Brown; K. Karalis; C. Pothoulakis. Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation. Proceedings of the National Academy of Sciences 2004, 101, 8503 -8508.

AMA Style

Pauline Anton, J. Gay, A. Mykoniatis, A. Pan, Michael J O'Brien, D. Brown, K. Karalis, C. Pothoulakis. Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation. Proceedings of the National Academy of Sciences. 2004; 101 (22):8503-8508.

Chicago/Turabian Style

Pauline Anton; J. Gay; A. Mykoniatis; A. Pan; Michael J O'Brien; D. Brown; K. Karalis; C. Pothoulakis. 2004. "Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation." Proceedings of the National Academy of Sciences 101, no. 22: 8503-8508.