Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk

IJssennagger, Noortje, Derrien, Muriel, van Doorn, Gerdien M, Rijnierse, Anneke, van den Bogert, Bartholomeus, Müller, Michael, Dekker, Jan, Kleerebezem, Michiel and van der Meer, Roelof (2012) Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk. PLoS One, 7 (12). ISSN 1932-6203

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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.

Item Type: Article
Additional Information: © 2012 IJssennagger et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords: animals,bacteroidetes,colon,diet,feces,heme,host-pathogen interactions,metagenome,mice,mucous membrane,philology,rna, ribosomal, 16s
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 03 Mar 2014 18:09
Last Modified: 21 Apr 2020 22:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/47642
DOI: 10.1371/journal.pone.0049868

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