title: Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk.
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.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Noortje
authors.initials: N
authors.lastname: Ĳssennagger
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.forename: Gerdien M
authors.initials: GM
authors.lastname: van Doorn
authors.forename: Anneke
authors.initials: A
authors.lastname: Rijnierse
authors.forename: Bartholomeus
authors.initials: B
authors.lastname: van den Bogert
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Jan
authors.initials: J
authors.lastname: Dekker
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleerebezem
authors.forename: Roelof
authors.initials: R
authors.lastname: van der Meer
mesh_terms: D000818:Animals; D041963:Bacteroidetes / Q000235:genetics; D003106:Colon / Q000382:microbiology*; D004032:Diet; D005243:Feces / Q000382:microbiology; D006418:Heme / Q000008:administration & dosage*; D054884:Host-Pathogen Interactions; D054892:Metagenome / Q000235:genetics*; D051379:Mice; D009092:Mucous Membrane / Q000382:microbiology; D010680:Philology; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D012336:RNA, Ribosomal, 16S; D006418:Heme