Gabriela Fragoso - Academia.edu (original) (raw)

Papers by Gabriela Fragoso

Research paper thumbnail of A34 Antibiotic Treatment and Oral Iron Supplementation Shape the Composition, Recovery and Function of the Gut Microbiota

Journal of the Canadian Association of Gastroenterology, Mar 1, 2021

Research paper thumbnail of Mo1587: RECOVERY OF THE GUT MICROBIOTA UNDER ORAL IRON SUPPLEMENTATION IS DELETERIOUS AND PROMOTES COLORECTAL CARCINEGENESIS

Gastroenterology, May 1, 2022

Research paper thumbnail of Supplementary Figure 4 from Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery

Research paper thumbnail of Supplementary Figure 3 from Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery

Supplementary Figure 3. Inulin and 5-ASA supplementation was associated with an improved gut barr... more Supplementary Figure 3. Inulin and 5-ASA supplementation was associated with an improved gut barrier integrity in mice. (A) Mice received a control diet or dietary supplementation with inulin or 5-ASA for 2 weeks and then received oral fluorescein isothiocyanate-dextran. (B) In vivo fluorescence. (C) Plasmatic and fecal fluorescence. N=5 per group. ANOVA with Tukey's post hoc test, bars represent means ± SEM. **P<0.01, ***P<0.001. Illustrations were created with BioRender.com.

Research paper thumbnail of Tu1539: INULIN EFFECT ON TUMORIGENICITY IN APC MICE DEPENDS ON THE PRESENCE OF COLIBACTIN-PRODUCING BACTERIA

Gastroenterology, May 1, 2022

Research paper thumbnail of Mo1598: THE MODULATION OF INTESTINAL INFLAMMATION BY PARABACTEROIDES GOLDSTEINII IN MURINE MODELS OF COLITIS

Gastroenterology, May 1, 2022

Research paper thumbnail of Inulin and Galacto-oligosaccharides Increase the Genotoxic Effect of Colibactin Produced by pks+ Escherichia Coli Strains

Background: Colibactin is a genotoxin that induces double-strand DNA breaks and is produced by Es... more Background: Colibactin is a genotoxin that induces double-strand DNA breaks and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactinproducing gut bacteria promote carcinogenesis and enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. Methods: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 µM, 25 µM and 125 µM of iron sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immuno uorescence analysis. Results: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 µM of iron sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and double-strand DNA breaks in Caco-2 cells compared to untreated cells. Conclusion: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether these results are reproducible in vivo.

Research paper thumbnail of Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer

Gut Pathogens, Dec 28, 2022

Background: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common... more Background: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Methods: Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR. Results: We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%). Conclusions: Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.

Research paper thumbnail of Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota

BMC Microbiology, Sep 28, 2021

Background: Oral iron supplementation is commonly prescribed for anemia and may play an important... more Background: Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. This study aims to investigate the effects of iron supplementation on gut microbiota recovery after antibiotics exposure. Results: Mice were subjected to oral antibiotic treatment with neomycin and metronidazole and were fed diets with different concentrations of iron. The composition of the gut microbiota was followed throughout treatment by 16S rRNA sequencing of DNA extracted from fecal samples. Gut microbiota functions were inferred using PICRUSt2, and short-chain fatty acid concentration in fecal samples was assessed by liquid-chromatography mass spectrometry. Iron supplementation after antibiotic exposure shifted the gut microbiota composition towards a Bacteroidetes phylumdominant composition. At the genus level, the iron-supplemented diet induced an increase in the abundance of Parasutterella and Bacteroides, and a decrease of Bilophila and Akkermansia. Parasutterella excrementihominis, Bacteroides vulgatus, and Alistipes finegoldii, were more abundant with the iron excess diet. Iron-induced shifts in microbiota composition were accompanied by functional modifications, including an enhancement of the biosynthesis of primary bile acids, nitrogen metabolism, cyanoamino acid metabolism and pentose phosphate pathways. Recovery after antibiotic treatment increased propionate levels independent of luminal iron levels, whereas butyrate levels were diminished by excess iron. Conclusions: Oral iron supplementation after antibiotic therapy in mice may lead to deleterious changes in the recovery of the gut microbiota. Our results have implications on the use of oral iron supplementation after antibiotic exposure and justify further studies on alternative treatments for anemia in these settings.

Research paper thumbnail of Oligosaccharides increase the genotoxic effect of colibactin produced by pks+ Escherichia coli strains

BMC Cancer, Feb 17, 2021

Background: Colibactin is a genotoxin that induces DNA double-strand breaks that may lead to carc... more Background: Colibactin is a genotoxin that induces DNA double-strand breaks that may lead to carcinogenesis and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactin-producing gut bacteria promote carcinogenesis and enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. Methods: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 μM, 25 μM and 125 μM of ferrous sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immunofluorescence analysis. Results: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 μM of ferrous sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and DNA double-strand breaks in Caco-2 cells compared to untreated cells. Conclusion: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether oligosaccharide supplementation may lead to increased colorectal tumorigenesis in animal models colonized with pks+ E. coli.

Research paper thumbnail of A271 the Modulation of Intestinal Inflammation by Parabacteroides Goldsteinii in Experimental Murine Colitis

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerativ... more Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerative colitis, are

Research paper thumbnail of A269 the Modulation of Intestinal Inflammation by Parabacteroides Goldsteinii in Murine Models of Colitis

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerativ... more Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerative colitis, are

Research paper thumbnail of A202 Investigation of the Direct Effect of Hemin-Hemopexin and Haptoglobin Stimulation in Inflammatory Bowel Disease

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Research paper thumbnail of IDDF2022-ABS-0260 Targeting GUT microbiota to prevent anastomotic tumors and distant metastasis in colorectal cancer surgery

Research paper thumbnail of IDDF2022-ABS-0219 Recovery of the gut microbiota under oral iron supplementation is deleterious and promotes colorectal carcinogenesis in <i>APC<sup>Min/+</sup></i> mice

Research paper thumbnail of MyD88 Adaptor Protein Is Required for Appropriate Hepcidin Induction in Response to Dietary Iron Overload in Mice

Frontiers in Physiology, Mar 5, 2018

Iron homeostasis is tightly regulated to provide virtually all cells in the body, particularly re... more Iron homeostasis is tightly regulated to provide virtually all cells in the body, particularly red blood cells, with this essential element while defending against its toxicity. The peptide hormone hepcidin is central to the control of the amount of iron absorbed from the diet and iron recycling from macrophages. Previously, we have shown that hepcidin induction in macrophages following Toll-like receptor (TLR) stimulation depends on the presence of myeloid differentiation primary response gene 88 (MyD88). In this study, we analyzed the regulation of iron metabolism in MyD88 −/− mice to further investigate MyD88 involvement in iron sensing and hepcidin induction. We show that mice lacking MyD88 accumulate significantly more iron in their livers than wild-type counterparts in response to dietary iron loading as they are unable to appropriately control hepcidin levels. The defect was associated with inappropriately low levels of Smad4 protein and Smad1/5/8 phosphorylation in liver samples found in the MyD88 −/− mice compared to wild-type mice. In conclusion, our results reveal a previously unknown link between MyD88 and iron homeostasis, and provide new insights into the regulation of hepcidin through the iron-sensing pathway.

Research paper thumbnail of Curcumin induces mild anemia in a DSS-induced colitis mouse model maintained on an iron-sufficient diet

Research paper thumbnail of A264 Oral Iron Supplementation Shapes the Recovery of Gut the Microbiota and Promotes Carcinogenesis in the Apcmin/+ Mouse Model

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Research paper thumbnail of Glycine stimulation of glutamate binding to chick retinal pigment epithelium

Neurochemical Research, Aug 1, 1995

The effect of glycine (Gly) and taurine (Tau) on the biochemical and pharmacological properties o... more The effect of glycine (Gly) and taurine (Tau) on the biochemical and pharmacological properties of [3H]l-glutamate ([3H] Glu) binding to membranes from primary cultures of chick retinal pigment epithelium (RPE), as well as from intact tissue during development was studied. Gly and Tau increase Bmax of [3H]Glu binding to a high affinity site (KB=300 nM) in membranes from 16 days in vitro (immature) cultures; additionally, Gly discloses a low affinity Glu-binding site (KB=970 nM) at this stage. In membranes from 25 days in vitro (mature) cultures, the high affinity site is no longer present and Tau has no effect on Glu-binding; Gly still stimulates binding to the low affinity site by four fold, with an EC50=200 μM. Pharmacological profile using specific excitatory amino acid (EAA) receptor agonists and antagonists suggests that at 16 days in vitro Glu binds preferentially to metabotropic Glu receptors (mGluRs), and at 25 days in vitro to ionotropic receptors different from neuronal ones. The stimulatory effect of Gly and Tau was also observed in intact RPE, and decreased with increasing embryonic age. Glu binding was also stimulated in membranes from chick retina, but not in those from rat brain. Results support the possibility of EAA participation in several aspects of RPE physiology, including phagocytosis and cell division.

Research paper thumbnail of Excitatory amino acid-induced inositol phosphate formation in cultured retinal pigment epithelium

Visual Neuroscience, Mar 1, 1999

Excitatory amino acid (EAA)-induced production of inositolphosphates (IPs) was studied in primary... more Excitatory amino acid (EAA)-induced production of inositolphosphates (IPs) was studied in primary cultures of chick retinal pigment epithelium (RPE) following in vitro incorporation of [ 3 H] myo-inositol. Glutamic acid (L-glu) significantly increased [ 3 H]-IPs accumulation (215%). L-glu agonists stimulated [ 3 H]IPs accumulation in the following order of efficiency: N-methyl-D-aspartate (NMDA) Ն L-glu Ͼ quisqualate Ն kainate Ͼ (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Stimulation was dependent on external Ca 2ϩ. The NMDA-induced response was blocked by (ϩ)-5-methyl-10,11-dihydro-5H-dibenzo-cyclohepten-5,10-imine maleate (MK-801) and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and was decreased by the L-Ca 2ϩ-channel blockers verapamil and nifedipine as well as by dantrolene. The metabotropic glutamate receptor (mGluR) antagonist (ϩ)-a-methyl-4-carboxyphenylglycine (ϩ)MCPG inhibited 3,5-dihydroxyphenylglycine (DHPG) and ACPD-induced stimulation, which demonstrates the presence in RPE of mGluRs 1 and0or 5, as well as NMDA receptors coupled directly, or through the influx of external Ca 2ϩ , to phospholipase C activation. L-glu agonists showed no effect either on basal level of intracellular cyclic adenosine monophosphate, nor on forskolin-or carbachol-induced stimulation of adenylyl cyclase. Since L-glu is released from the retina upon illumination, and receptors for this compound are present in RPE, the activation of the inositide pathway could be involved in the regulation of retina-RPE interaction, which is essential for the visual process.

Research paper thumbnail of A34 Antibiotic Treatment and Oral Iron Supplementation Shape the Composition, Recovery and Function of the Gut Microbiota

Journal of the Canadian Association of Gastroenterology, Mar 1, 2021

Research paper thumbnail of Mo1587: RECOVERY OF THE GUT MICROBIOTA UNDER ORAL IRON SUPPLEMENTATION IS DELETERIOUS AND PROMOTES COLORECTAL CARCINEGENESIS

Gastroenterology, May 1, 2022

Research paper thumbnail of Supplementary Figure 4 from Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery

Research paper thumbnail of Supplementary Figure 3 from Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery

Supplementary Figure 3. Inulin and 5-ASA supplementation was associated with an improved gut barr... more Supplementary Figure 3. Inulin and 5-ASA supplementation was associated with an improved gut barrier integrity in mice. (A) Mice received a control diet or dietary supplementation with inulin or 5-ASA for 2 weeks and then received oral fluorescein isothiocyanate-dextran. (B) In vivo fluorescence. (C) Plasmatic and fecal fluorescence. N=5 per group. ANOVA with Tukey's post hoc test, bars represent means ± SEM. **P<0.01, ***P<0.001. Illustrations were created with BioRender.com.

Research paper thumbnail of Tu1539: INULIN EFFECT ON TUMORIGENICITY IN APC MICE DEPENDS ON THE PRESENCE OF COLIBACTIN-PRODUCING BACTERIA

Gastroenterology, May 1, 2022

Research paper thumbnail of Mo1598: THE MODULATION OF INTESTINAL INFLAMMATION BY PARABACTEROIDES GOLDSTEINII IN MURINE MODELS OF COLITIS

Gastroenterology, May 1, 2022

Research paper thumbnail of Inulin and Galacto-oligosaccharides Increase the Genotoxic Effect of Colibactin Produced by pks+ Escherichia Coli Strains

Background: Colibactin is a genotoxin that induces double-strand DNA breaks and is produced by Es... more Background: Colibactin is a genotoxin that induces double-strand DNA breaks and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactinproducing gut bacteria promote carcinogenesis and enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. Methods: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 µM, 25 µM and 125 µM of iron sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immuno uorescence analysis. Results: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 µM of iron sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and double-strand DNA breaks in Caco-2 cells compared to untreated cells. Conclusion: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether these results are reproducible in vivo.

Research paper thumbnail of Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer

Gut Pathogens, Dec 28, 2022

Background: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common... more Background: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Methods: Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR. Results: We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%). Conclusions: Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.

Research paper thumbnail of Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota

BMC Microbiology, Sep 28, 2021

Background: Oral iron supplementation is commonly prescribed for anemia and may play an important... more Background: Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. This study aims to investigate the effects of iron supplementation on gut microbiota recovery after antibiotics exposure. Results: Mice were subjected to oral antibiotic treatment with neomycin and metronidazole and were fed diets with different concentrations of iron. The composition of the gut microbiota was followed throughout treatment by 16S rRNA sequencing of DNA extracted from fecal samples. Gut microbiota functions were inferred using PICRUSt2, and short-chain fatty acid concentration in fecal samples was assessed by liquid-chromatography mass spectrometry. Iron supplementation after antibiotic exposure shifted the gut microbiota composition towards a Bacteroidetes phylumdominant composition. At the genus level, the iron-supplemented diet induced an increase in the abundance of Parasutterella and Bacteroides, and a decrease of Bilophila and Akkermansia. Parasutterella excrementihominis, Bacteroides vulgatus, and Alistipes finegoldii, were more abundant with the iron excess diet. Iron-induced shifts in microbiota composition were accompanied by functional modifications, including an enhancement of the biosynthesis of primary bile acids, nitrogen metabolism, cyanoamino acid metabolism and pentose phosphate pathways. Recovery after antibiotic treatment increased propionate levels independent of luminal iron levels, whereas butyrate levels were diminished by excess iron. Conclusions: Oral iron supplementation after antibiotic therapy in mice may lead to deleterious changes in the recovery of the gut microbiota. Our results have implications on the use of oral iron supplementation after antibiotic exposure and justify further studies on alternative treatments for anemia in these settings.

Research paper thumbnail of Oligosaccharides increase the genotoxic effect of colibactin produced by pks+ Escherichia coli strains

BMC Cancer, Feb 17, 2021

Background: Colibactin is a genotoxin that induces DNA double-strand breaks that may lead to carc... more Background: Colibactin is a genotoxin that induces DNA double-strand breaks that may lead to carcinogenesis and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactin-producing gut bacteria promote carcinogenesis and enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. Methods: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 μM, 25 μM and 125 μM of ferrous sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immunofluorescence analysis. Results: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 μM of ferrous sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and DNA double-strand breaks in Caco-2 cells compared to untreated cells. Conclusion: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether oligosaccharide supplementation may lead to increased colorectal tumorigenesis in animal models colonized with pks+ E. coli.

Research paper thumbnail of A271 the Modulation of Intestinal Inflammation by Parabacteroides Goldsteinii in Experimental Murine Colitis

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerativ... more Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerative colitis, are

Research paper thumbnail of A269 the Modulation of Intestinal Inflammation by Parabacteroides Goldsteinii in Murine Models of Colitis

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerativ... more Background: Inflammatory bowel diseases (IBDs), comprised mainly of Crohn's disease and ulcerative colitis, are

Research paper thumbnail of A202 Investigation of the Direct Effect of Hemin-Hemopexin and Haptoglobin Stimulation in Inflammatory Bowel Disease

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Research paper thumbnail of IDDF2022-ABS-0260 Targeting GUT microbiota to prevent anastomotic tumors and distant metastasis in colorectal cancer surgery

Research paper thumbnail of IDDF2022-ABS-0219 Recovery of the gut microbiota under oral iron supplementation is deleterious and promotes colorectal carcinogenesis in <i>APC<sup>Min/+</sup></i> mice

Research paper thumbnail of MyD88 Adaptor Protein Is Required for Appropriate Hepcidin Induction in Response to Dietary Iron Overload in Mice

Frontiers in Physiology, Mar 5, 2018

Iron homeostasis is tightly regulated to provide virtually all cells in the body, particularly re... more Iron homeostasis is tightly regulated to provide virtually all cells in the body, particularly red blood cells, with this essential element while defending against its toxicity. The peptide hormone hepcidin is central to the control of the amount of iron absorbed from the diet and iron recycling from macrophages. Previously, we have shown that hepcidin induction in macrophages following Toll-like receptor (TLR) stimulation depends on the presence of myeloid differentiation primary response gene 88 (MyD88). In this study, we analyzed the regulation of iron metabolism in MyD88 −/− mice to further investigate MyD88 involvement in iron sensing and hepcidin induction. We show that mice lacking MyD88 accumulate significantly more iron in their livers than wild-type counterparts in response to dietary iron loading as they are unable to appropriately control hepcidin levels. The defect was associated with inappropriately low levels of Smad4 protein and Smad1/5/8 phosphorylation in liver samples found in the MyD88 −/− mice compared to wild-type mice. In conclusion, our results reveal a previously unknown link between MyD88 and iron homeostasis, and provide new insights into the regulation of hepcidin through the iron-sensing pathway.

Research paper thumbnail of Curcumin induces mild anemia in a DSS-induced colitis mouse model maintained on an iron-sufficient diet

Research paper thumbnail of A264 Oral Iron Supplementation Shapes the Recovery of Gut the Microbiota and Promotes Carcinogenesis in the Apcmin/+ Mouse Model

Journal of the Canadian Association of Gastroenterology, Mar 1, 2023

Research paper thumbnail of Glycine stimulation of glutamate binding to chick retinal pigment epithelium

Neurochemical Research, Aug 1, 1995

The effect of glycine (Gly) and taurine (Tau) on the biochemical and pharmacological properties o... more The effect of glycine (Gly) and taurine (Tau) on the biochemical and pharmacological properties of [3H]l-glutamate ([3H] Glu) binding to membranes from primary cultures of chick retinal pigment epithelium (RPE), as well as from intact tissue during development was studied. Gly and Tau increase Bmax of [3H]Glu binding to a high affinity site (KB=300 nM) in membranes from 16 days in vitro (immature) cultures; additionally, Gly discloses a low affinity Glu-binding site (KB=970 nM) at this stage. In membranes from 25 days in vitro (mature) cultures, the high affinity site is no longer present and Tau has no effect on Glu-binding; Gly still stimulates binding to the low affinity site by four fold, with an EC50=200 μM. Pharmacological profile using specific excitatory amino acid (EAA) receptor agonists and antagonists suggests that at 16 days in vitro Glu binds preferentially to metabotropic Glu receptors (mGluRs), and at 25 days in vitro to ionotropic receptors different from neuronal ones. The stimulatory effect of Gly and Tau was also observed in intact RPE, and decreased with increasing embryonic age. Glu binding was also stimulated in membranes from chick retina, but not in those from rat brain. Results support the possibility of EAA participation in several aspects of RPE physiology, including phagocytosis and cell division.

Research paper thumbnail of Excitatory amino acid-induced inositol phosphate formation in cultured retinal pigment epithelium

Visual Neuroscience, Mar 1, 1999

Excitatory amino acid (EAA)-induced production of inositolphosphates (IPs) was studied in primary... more Excitatory amino acid (EAA)-induced production of inositolphosphates (IPs) was studied in primary cultures of chick retinal pigment epithelium (RPE) following in vitro incorporation of [ 3 H] myo-inositol. Glutamic acid (L-glu) significantly increased [ 3 H]-IPs accumulation (215%). L-glu agonists stimulated [ 3 H]IPs accumulation in the following order of efficiency: N-methyl-D-aspartate (NMDA) Ն L-glu Ͼ quisqualate Ն kainate Ͼ (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Stimulation was dependent on external Ca 2ϩ. The NMDA-induced response was blocked by (ϩ)-5-methyl-10,11-dihydro-5H-dibenzo-cyclohepten-5,10-imine maleate (MK-801) and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and was decreased by the L-Ca 2ϩ-channel blockers verapamil and nifedipine as well as by dantrolene. The metabotropic glutamate receptor (mGluR) antagonist (ϩ)-a-methyl-4-carboxyphenylglycine (ϩ)MCPG inhibited 3,5-dihydroxyphenylglycine (DHPG) and ACPD-induced stimulation, which demonstrates the presence in RPE of mGluRs 1 and0or 5, as well as NMDA receptors coupled directly, or through the influx of external Ca 2ϩ , to phospholipase C activation. L-glu agonists showed no effect either on basal level of intracellular cyclic adenosine monophosphate, nor on forskolin-or carbachol-induced stimulation of adenylyl cyclase. Since L-glu is released from the retina upon illumination, and receptors for this compound are present in RPE, the activation of the inositide pathway could be involved in the regulation of retina-RPE interaction, which is essential for the visual process.