Campbell, B

Mahalhal, A

Pritchard, DM

Probert, C

University of Liverpool Repository

Influence of iron on gut microbial composition in acute DSS-induced colitis in C57BL/6 mice   Mahalhal A., Campbell B.J., Pritchard D.M., Probert C.S.  Introduction: Iron deficiency anaemia is common in inflammatory bowel disease (IBD). Iron supplementation may induce or exacerbate colitis in rats (APT 2001; 15:1989-99). Dysbiosis is common in IBD and iron contributes to this as it is a growth factor for some bacteria. We investigated the acute effect of dietary iron supplementation and/or reduction on the intestinal microbiome in a murine model of colitis. We report results of changes at the phylum level.   Methods: Studies were performed on six groups of wild-type mice (6/group). Acute colitis was induced with 2% dextran sodium sulphate (DSS) for 5 days, followed by 5 further days on water.  DSS-treated mice were fed one of three diets (from day-1 of DSS treatment): Low iron [LI] (100ppm), normal iron [NI] (200ppm) and high iron [HI] supplemented (400ppm) chow. Also, three non-DSS-treated groups were studied and fed similarly. Clinical and pathological data were compared. At day-1 vs. day-10, bacterial gDNA was extracted from faeces and microbiota composition determined from the sequence of V4 region of 16S rDNA on the Illumina MiSeq platform. Statistical inferences were made using Welch’s t-test with post-hoc analysis (Bioinformatics 2010; 26:715-21).    The results: DSS-induced colitis was exacerbated in LI and HI groups, more so in LI mice (as determined by mean total body weight loss [9.2%, at day-8] and significantly worse histology; median score 2.5, at day-10). However, faecal phyla changes were only seen following DSS treatment in the HI group at day-10 vs. day-1 with increased Proteobacteria (P <1.38e-3), Actinobacteria (P <5.13e-3) and Fusobacteria (P <3.25e-3), and decreased Firmicutes (P <6.96e-3) and Bacteroidetes (P <5.98e-3).   Conclusion: DSS-induced colitis occurred in each group, but the severity was greatest in mice on low or high iron diets. Dysbiosis was only evident in mice receiving the high iron diet. These data suggest that 1) luminal iron may influence the severity of colitis, but 2) dysbiosis occurred when DSS was administered with the high iron diet, but not with low and normal iron diets. These findings suggest a role for iron in the dysbiosis seen during relapse of IBD and likely GI symptoms following iron supplementation.    Figure 1: Extended error bar plot for the five phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria) that have a difference between the proportions of day-1 and day-10 for 400pm iron DSS-treated mice. This post-hoc plot for each phylum indicating 1) the mean proportion of sequences at day-1 and-10, 2) the difference in mean proportions for each phylum comparing pre and post-DSS treatment, and 3) a p-value indicating if the mean proportion is equal for each time point. Statistical differences were assessed by Welch’s t-test followed by Storey’s FDR multiple test correction. 

INFLUENCE OF IRON ON GUT MICROBIAL COMPOSITION IN ACUTE DSS-INDUCED COLITIS IN C57BL/6 MICE

http://livrepository.liverpool.ac.uk/3027459/1/BSG%202017%20%281%29%20final%20draft.pdf

INFLUENCE OF IRON ON GUT MICROBIAL COMPOSITION IN ACUTE DSS-INDUCED COLITIS IN C57BL/6 MICE

Abstract

Similar works

Full text

Available Versions

University of Liverpool Repository