Dietary Heme Alters Microbiota and Mucosa of Mouse Colon without Functional Changes in Host-Microbe Cross-Talk
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{"title"=>"Dietary Heme Alters Microbiota and Mucosa of Mouse Colon without Functional Changes in Host-Microbe Cross-Talk", "type"=>"journal", "authors"=>[{"first_name"=>"Noortje", "last_name"=>"IJssennagger", "scopus_author_id"=>"23008571200"}, {"first_name"=>"Muriel", "last_name"=>"Derrien", "scopus_author_id"=>"7003711373"}, {"first_name"=>"Gerdien M.", "last_name"=>"van Doorn", "scopus_author_id"=>"55523970900"}, {"first_name"=>"Anneke", "last_name"=>"Rijnierse", "scopus_author_id"=>"13009135900"}, {"first_name"=>"Bartholomeus", "last_name"=>"van den Bogert", "scopus_author_id"=>"46261644400"}, {"first_name"=>"Michael", "last_name"=>"Müller", "scopus_author_id"=>"7404689194"}, {"first_name"=>"Jan", "last_name"=>"Dekker", "scopus_author_id"=>"17338202900"}, {"first_name"=>"Michiel", "last_name"=>"Kleerebezem", "scopus_author_id"=>"7007148445"}, {"first_name"=>"Roelof", "last_name"=>"van der Meer", "scopus_author_id"=>"55400857800"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23239972", "doi"=>"10.1371/journal.pone.0049868", "sgr"=>"84871142014", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "scopus"=>"2-s2.0-84871142014", "issn"=>"19326203", "pui"=>"366273711"}, "id"=>"3833a35d-4da4-3e74-b262-5ae47a9c15cc", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/dietary-heme-alters-microbiota-mucosa-mouse-colon-without-functional-changes-hostmicrobe-crosstalk", "reader_count"=>73, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>3, "Student > Master"=>14, "Other"=>6, "Student > Bachelor"=>4, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>3, "Student > Master"=>14, "Other"=>6, "Student > Bachelor"=>4, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>33, "Medicine and Dentistry"=>12, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>7}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>7}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>33}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>7}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Netherlands"=>1, "United States"=>2, "Japan"=>1, "United Kingdom"=>1, "Switzerland"=>1, "India"=>1, "Russia"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/527086"], "description"=>"<p>Histological staining was performed for H&E, AB-PAS, HID and Alpi. Ki67-immunohistochemistry was performed using a Ki67-specific antibody.</p>", "links"=>[], "tags"=>["staining", "colonic", "mucosa", "14", "days", "heme"], "article_id"=>197562, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.g001", "stats"=>{"downloads"=>1, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_staining_of_mouse_colonic_mucosa_after_14_days_on_control_or_heme_diet_/197562", "title"=>"Histological staining of mouse colonic mucosa after 14 days on control or heme diet.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:06:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/527644"], "description"=>"<p>Data are represented as mean ± SEM, n = 8 for feces and mucosal histology and n = 4 for gene expression.</p>*<p>Significantly different from respective controls at q<0.01 for gene expression and p<0.05 for other parameters.</p>", "links"=>[], "tags"=>["dietary", "heme", "fecal", "mucosal"], "article_id"=>198133, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_effects_of_dietary_heme_on_fecal_and_mucosal_parameters_/198133", "title"=>"Differential effects of dietary heme on fecal and mucosal parameters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-12-11 02:15:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/284650", "https://ndownloader.figshare.com/files/284722", "https://ndownloader.figshare.com/files/284788", "https://ndownloader.figshare.com/files/284866"], "description"=>"<div><p>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 <em>Bacteroides</em> 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.</p> </div>", "links"=>[], "tags"=>["dietary", "heme", "alters", "microbiota", "mucosa", "colon", "changes", "host-microbe", "cross-talk"], "article_id"=>116110, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049868.s001", "https://dx.doi.org/10.1371/journal.pone.0049868.s002", "https://dx.doi.org/10.1371/journal.pone.0049868.s003", "https://dx.doi.org/10.1371/journal.pone.0049868.s004"], "stats"=>{"downloads"=>18, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dietary_Heme_Alters_Microbiota_and_Mucosa_of_Mouse_Colon_without_Functional_Changes_in_Host_Microbe_Cross_Talk__/116110", "title"=>"Dietary Heme Alters Microbiota and Mucosa of Mouse Colon without Functional Changes in Host-Microbe Cross-Talk", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-12-11 01:41:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/527447"], "description"=>"<p>Western blot (A) shows the presence of Slpi protein colon scraping homogenate pools (n = 8 for both groups) of heme-fed mice. Slpi is not detectable in controls. β-actin serves as a loading control. (B) Gene expression levels (A and B) in total scrapings are based on microarray analysis on individual mice (n = 4 per group). Relative gene expression changes (fold-changes) on heme were calculated by setting RNA levels of control mice to 1 (mean ± SEM, *q<0.01). Surface- and crypt-specific microarray gene expression profiles are from pooled tissue samples obtained by LCM (n = 4 controls, n = 3 heme-fed mice). In this LCM experiment also total scrapings were again collected and analyzed by microarray. Surface and crypt expression values are normalized for the expression in total scrapings.</p>", "links"=>[], "tags"=>["levels", "slpi", "dio1"], "article_id"=>197930, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_and_protein_levels_of_Slpi_and_gene_expression_levels_of_Alpi_Dio1_and_Hspa1a_/197930", "title"=>"Gene expression and protein levels of Slpi and gene expression levels of Alpi, Dio1 and Hspa1a.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:12:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/527206"], "description"=>"<p>Gel-view figure of the intensity of 3,580 probes covered by MITChip and assigned to the phylogenetic class-like groups (level 1) depicted on the right side. Ward's minimum variance method was used to generate hierarchical clustering of the total microbiota probe profiles, whereas the distance matrix between the samples was based on the Pearson's product moment correlation.</p>", "links"=>[], "tags"=>["fingerprints", "colonic", "microbiota", "heme"], "article_id"=>197687, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.g002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogenetic_fingerprints_of_the_colonic_microbiota_of_the_control_group_and_heme_group_/197687", "title"=>"Phylogenetic fingerprints of the colonic microbiota of the control group and heme group.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:08:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/527607"], "description"=>"<p>Data are represented as mean ± SEM (n = 8),</p>*<p>q<0.05,</p>**<p>q<0.01.</p><p>significance indicated between the control group and the heme group tested by Mann Whitney corrected for multiple testing by Benjamini-Hochberg procedure.</p>", "links"=>[], "tags"=>["bacterial", "classes-", "clusters", "mitchip", "heme-fed"], "article_id"=>198085, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.t002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_contribution_of_bacterial_classes_Clostridium_clusters_level_1_detected_by_MITChip_in_control_and_heme_fed_mice_/198085", "title"=>"Relative contribution of bacterial classes- <i>Clostridium</i> clusters (level 1) detected by MITChip in control and heme-fed mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-12-11 02:14:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/527562"], "description"=>"<p>Data are represented as mean ± SEM, (n = 8).</p>*<p>indicates significant change between control and heme (p<0.05),</p>**<p>indicates significant change between control and heme (p<0.001).</p><p>For ratio calculation, the in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049868#pone-0049868-t002\" target=\"_blank\">Table 2</a> quantified Actinobacteria, Firmicutes and TM7 were included as Gram-positives and Bacteroidetes, Deferribacterres, Fibrobacteres, Fusobacteria, Proteobacteria and Verrucomicrobia were included as Gram-negatives.</p><p><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049868#s3\" target=\"_blank\">Results</a> are expressed in log10 of gene copy-nr/g fecal dry weight. Genes used for quantification are mentioned between brackets.</p>", "links"=>[], "tags"=>["genes", "colonic", "samples", "heme-fed"], "article_id"=>198038, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.t003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantification_of_total_bacteria_and_specific_functional_genes_in_colonic_samples_from_control_and_heme_fed_mice_/198038", "title"=>"Quantification of total bacteria and specific functional genes in colonic samples from control and heme-fed mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-12-11 02:13:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/527349"], "description"=>"<p>Fecal water pools from four separate, but identical, animal experiments were used in triplicate. Viability is measured relative to PBS (A) and control fecal water (B). Data are presented as mean ± SEM, (n = 4) *p<0.05.</p>", "links"=>[], "tags"=>["deoxycholate", "heme", "fecal", "viability", "gram-negative", "gram-positive"], "article_id"=>197828, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_effect_of_deoxycholate_A_and_of_control_and_heme_fecal_water_B_on_viability_of_Gram_negative_G_E_coli_and_Gram_positive_G_L_plantarum_/197828", "title"=>"Differential effect of deoxycholate (A) and of control and heme fecal water (B) on viability of Gram-negative (G−) <i>E.coli</i> and Gram-positive (G+) <i>L. plantarum</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:10:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/527677"], "description"=>"*<p>indicates significant fold change (q<0.01), genes with signal intensities below.</p><p>20 are considered not expressed (n.e.).</p>", "links"=>[], "tags"=>["heme"], "article_id"=>198166, "categories"=>["Molecular Biology", "Microbiology", "Biochemistry", "Chemistry", "Cancer", "Biological Sciences"], "users"=>["Noortje IJssennagger", "Muriel Derrien", "Gerdien M. van Doorn", "Anneke Rijnierse", "Bartholomeus van den Bogert", "Michael Müller", "Jan Dekker", "Michiel Kleerebezem", "Roelof van der Meer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049868.t004", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mucosal_gene_expression_on_control_or_heme_diet_/198166", "title"=>"Mucosal gene expression on control or heme diet.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-12-11 02:16:06"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Anatomy and physiology", "average_usage"=>[307, 540, 660, 756, 847, 936, 1025, 1111, 1199, 1282, 1361, 1432]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[316, 541, 663, 766, 856, 950, 1041, 1128, 1218, 1302, 1382, 1456, 1526, 1593, 1657, 1729, 1796, 1862, 1930, 1999, 2065, 2132, 2202, 2261, 2319]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[333, 576, 707, 814, 908, 1004, 1104, 1197, 1280, 1370, 1449, 1531, 1603, 1673, 1742, 1817, 1886, 1954, 2025, 2098, 2171, 2234, 2304, 2365, 2431]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[307, 529, 649, 751, 845, 936, 1025, 1113, 1197, 1284, 1360, 1432, 1501, 1570, 1632, 1697, 1765, 1834, 1904, 1972, 2041, 2107, 2170, 2231, 2292]}, {"subject_area"=>"/Medicine and health sciences/Nutrition", "average_usage"=>[307, 546, 676, 780, 888, 986, 1099, 1202, 1282, 1376, 1468, 1552, 1627, 1713, 1774, 1875, 1944, 2011, 2079, 2133, 2210, 2282, 2358, 2422, 2480]}]}
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