Dietary heme modulates microbiota and mucosa of mouse colon without significant host-microbe cross talk
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE34253 | GEO | 2013/07/18
SECONDARY ACCESSION(S): PRJNA149753
REPOSITORIES: GEO
Similar Datasets
Project description:Previously, we showed that dietary heme injured the colonic surface epithelium and induced hyperproliferation by changing the surface to crypt signaling. In this study we investigated whether bacteria play a role in this changed signaling. Dietary heme increased the Bacteroidetes and decreased the Firmicutes in colonic content. This shift was caused by a selective susceptibility of Gram-positive bacteria to the heme cytotoxic fecal waters, which is not observed for Gram-negative bacteria allowing expansion of the Gram-negative community. The increased amount of Gram-negative bacteria increased LPS exposure to colonocytes, however, there is no appreciable immune response detected in the heme-fed mice. There were no signs of sensing of the bacteria by the mucosa, as changes in TLR signaling were not present. This lack of microbe-host cross talk indicated that the changes in microbiota do not play a causal role in the heme-induced hyperproliferation. Mice received control or heme diet for 14 days, whereafter pooled colon samples were analysed on microarrays.
2013-07-18 | E-GEOD-34253 | biostudies-arrayexpress
Project description:Colon cancer is a major cause of cancer deaths in Western countries and is associated with diets high in red meat. Heme, the iron-porphyrin pigment of red meat, induces cytotoxicity of gut contents which injures surface cells leading to compensatory hyperproliferation of crypt cells. This hyperproliferation results in epithelial hyperplasia which increases the risk of colon cancer. In humans, a high red-meat diet increases Bacteroides spp in feces. Therefore, we simultaneously investigated the effects of dietary heme on colonic microbiota and on the host mucosa of mice. Whole genome microarrays showed that heme injured the colonic surface epithelium and induced hyperproliferation by changing the surface to crypt signaling. Using 16S rRNA phylogenetic microarrays, we investigated whether bacteria play a role in this changed signaling. Heme increased Bacteroidetes and decreased Firmicutes in colonic contents. This shift was most likely caused by a selective susceptibility of Gram-positive bacteria to heme cytotoxic fecal water, which is not observed for Gram-negative bacteria, allowing expansion of the Gram-negative community. The increased amount of Gram-negative bacteria most probably increased LPS exposure to colonocytes, however, there is no appreciable immune response detected in the heme-fed mice. There was no functional change in the sensing of the bacteria by the mucosa, as changes in inflammation pathways and Toll- like receptor signaling were not detected. This unaltered host-microbe cross-talk indicates that the changes in microbiota did not play a causal role in the observed hyperproliferation and hyperplasia. Keywords: Expression profiling by array Mice were fed a Westernized high fat control diet, or the same diet supplemented with 0.5 M-BM-5mol heme/g diet. After 14 days of intervention, mice were killed and gene expression was profiled in colon.
2012-12-19 | E-GEOD-40672 | biostudies-arrayexpress
Project description:Colon cancer is a major cause of cancer deaths in Western countries and is associated with diets high in red meat. Heme, the iron-porphyrin pigment of red meat, induces cytotoxicity of gut contents which injures surface cells leading to compensatory hyperproliferation of crypt cells. This hyperproliferation results in epithelial hyperplasia which increases the risk of colon cancer. In humans, a high red-meat diet increases Bacteroides spp in feces. Therefore, we simultaneously investigated the effects of dietary heme on colonic microbiota and on the host mucosa of mice. Whole genome microarrays showed that heme injured the colonic surface epithelium and induced hyperproliferation by changing the surface to crypt signaling. Using 16S rRNA phylogenetic microarrays, we investigated whether bacteria play a role in this changed signaling. Heme increased Bacteroidetes and decreased Firmicutes in colonic contents. This shift was most likely caused by a selective susceptibility of Gram-positive bacteria to heme cytotoxic fecal water, which is not observed for Gram-negative bacteria, allowing expansion of the Gram-negative community. The increased amount of Gram-negative bacteria most probably increased LPS exposure to colonocytes, however, there is no appreciable immune response detected in the heme-fed mice. There was no functional change in the sensing of the bacteria by the mucosa, as changes in inflammation pathways and Toll- like receptor signaling were not detected. This unaltered host-microbe cross-talk indicates that the changes in microbiota did not play a causal role in the observed hyperproliferation and hyperplasia. Keywords: Expression profiling by array
2012-12-19 | GSE40672 | GEO
Project description:Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is compensated by hyperproliferation and hyperplasia of crypt cells, which was induced by a changed surface to crypt signalling as recently described. It is unknown whether the change in signaling is caused by cytotoxic stress and/or by oxidative stress, as these processes were never studied separately. Therefore, the aim of this study was to determine the possible differential effects of dietary heme on these luminal stressors and their impact on the colonic mucosa after 2, 4, 7 and 14 days of heme feeding. Mice received a purified humanized control diet or this diet supplemented with 0.2 µmol heme/g. Oxidative stress was measured as Thiobarbituric Acid Reactive Substances (TBARS) in fecal water. Cytotoxicity of fecal water was quantified with a bioassay. Epithelial cell proliferation was determined by Ki67 immunohistochemistry and mucosal responses were further studied in detail by whole genome transcriptomics. Dietary heme caused instantaneous and delayed changes in the luminal contents which were reflected in the mucosa. Instantaneous, there was an increase in reactive oxygen species leading to increased levels of lipid peroxidation products. Mucosal gene expression showed an instantaneous antioxidant response and PPAR target gene activation. After day 4 cytotoxicity of the colonic contents was increased and hyperproliferation was initiated, indicating that cytotoxicity was causal for the initiation of hyperproliferation. Several oncogenes were activated and tumor protein 53 was inhibited. In conclusion, dietary heme caused an instantaneous production of reactive oxygen species in mouse colon. A lag time was observed in the formation of cytotoxicity which coincided with the initiation hyperproliferation. Keywords: expression profiling by array Mice were fed a Westernized high fat control diet, or the same diet supplemented with 0.2 µmol heme/g diet. After different days of intervention, mice were killed and gene expression was profiled in colon.
2013-05-03 | E-GEOD-40671 | biostudies-arrayexpress
Project description:Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is compensated by hyperproliferation and hyperplasia of crypt cells, which was induced by a changed surface to crypt signalling as recently described. It is unknown whether the change in signaling is caused by cytotoxic stress and/or by oxidative stress, as these processes were never studied separately. Therefore, the aim of this study was to determine the possible differential effects of dietary heme on these luminal stressors and their impact on the colonic mucosa after 2, 4, 7 and 14 days of heme feeding. Mice received a purified humanized control diet or this diet supplemented with 0.2 µmol heme/g. Oxidative stress was measured as Thiobarbituric Acid Reactive Substances (TBARS) in fecal water. Cytotoxicity of fecal water was quantified with a bioassay. Epithelial cell proliferation was determined by Ki67 immunohistochemistry and mucosal responses were further studied in detail by whole genome transcriptomics. Dietary heme caused instantaneous and delayed changes in the luminal contents which were reflected in the mucosa. Instantaneous, there was an increase in reactive oxygen species leading to increased levels of lipid peroxidation products. Mucosal gene expression showed an instantaneous antioxidant response and PPAR target gene activation. After day 4 cytotoxicity of the colonic contents was increased and hyperproliferation was initiated, indicating that cytotoxicity was causal for the initiation of hyperproliferation. Several oncogenes were activated and tumor protein 53 was inhibited. In conclusion, dietary heme caused an instantaneous production of reactive oxygen species in mouse colon. A lag time was observed in the formation of cytotoxicity which coincided with the initiation hyperproliferation. Keywords: expression profiling by array
2013-05-03 | GSE40671 | GEO
Project description:The risk for colon cancer is associated with nutrition, especially high fat and low calcium diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation.
2011-10-02 | GSE27848 | GEO
Project description:The risk for colon cancer is associated with nutrition, especially with diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation.
2011-10-02 | GSE27847 | GEO
Project description:The risk for colon cancer is associated with nutrition, especially high fat and low calcium diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation. C57BL/6 mice received a Westernized high fat and low calcium diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. RNA was isolated from colon scrapings and subjected to gene expression profiling (n=7 control mice and n=9 heme-fed mice).
2011-10-01 | E-GEOD-27848 | biostudies-arrayexpress
Project description:The risk for colon cancer is associated with nutrition, especially with diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation. C57BL/6 mice received a Westernized diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. Swiss rolls were made from the middle 2 cm of the colon. These rolls were used for LCM, and surface cells and crypts cells were separately isolated. RNA was isolated from surface and crypt cells and subjected to gene expression profiling (n=4 control mice and n=3 heme-fed mice).
2011-10-01 | E-GEOD-27847 | biostudies-arrayexpress
Project description:Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upregulated lipid metabolism-related PPARM-NM-1 target genes. The aim of this study was to investigate the role of PPARM-NM-1 in heme-induced hyperproliferation and hyperplasia. Male PPARM-NM-1 KO and WT mice received a purified diet with or without heme. As PPARM-NM-1 is proposed to protect against oxidative stress and lipid peroxidation, we hypothesized that the absence of PPARM-NM-1 leads to more surface injury and crypt hyperproliferation in the colon upon heme-feeding. Heme induced luminal cytotoxicity and lipid peroxidation and colonic hyperproliferation and hyperplasia to the same extent in WT and KO mice. Transcriptome analysis of colonic mucosa confirmed similar heme-induced hyperproliferation in WT and KO mice. Stainings for alkaline phosphatase activity and expression levels of Vanin-1 and Nrf2-targets indicated a compromised antioxidant defense in heme-fed KO mice. Our results suggest that the protective role of PPARM-NM-1 in antioxidant defense involves the Nrf2-inhibitor Fosl1, which is upregulated by heme in PPARM-NM-1 KO mice. We conclude that PPARM-NM-1 plays a protective role in colon against oxidative stress, but PPARM-NM-1 does not mediate heme-induced hyperproliferation. This implies that oxidative stress of surface cells is not the main determinant of heme-induced hyperproliferation and hyperplasia. Wild type and peroxisome proliferator-activated receptor alpha (PPARM-NM-1) knockout mice were fed a Westernized high fat diet, or the same diet supplemented with 0.5 M-BM-5mol heme/g diet. After 14 days of intervention, mice were killed and gene expression was profiled in colon.
2012-08-22 | E-GEOD-37006 | biostudies-arrayexpress