Sex-related Alterations of Gut Microbiota in the C57BL/6 Mouse Model of Inflammatory Bowel Disease - PubMed (original) (raw)

Hee Jin Son et al. J Cancer Prev. 2019 Sep.

Abstract

Background: Gut microbiota is closely associated with development and exacerbation of inflammatory bowel diseases (IBD). The aim of this study was to investigate differences in gut microbiota depending on sex and changes of gut microbiota during IBD developments.

Methods: 16s rRNA metagenomic sequencing was performed for fecal materials from 8-week-old wild type (WT) and interleukin 10 (IL-10) knockout (KO) C57BL/6 mice of both sexes. Diversity indices, relative abundance of microbiota, and linear discriminant analysis effect size were examined to compare microbial communities between groups. Clustering of groups was performed by principal coordinates analysis (PCoA) and unweighted pair group method with arithmetic mean (UPGMA). Functional capabilities of microbiota were estimated using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) based on Kyoto Encyclopedia of Genes and Genomes database.

Results: PCoA and UPGMA tree analysis of beta-diversity demonstrated significant differences in gut microbiota between male and female groups of WT mice, but not of IL-10 KO mice. Firmicutes to Bacteroides ratio was higher in male group than that in female group in both WT mice and IL-10 KO mice. Phylum Proteobacteria significantly increased in female IL-10 KO mice than that in female WT mice. At species level, Lactobacillus murinus, Bacteroides acidifaciens, and Helicobacter hepaticus significantly increased in IL-10 KO mice than in WT mice. The relative abundance of beta-glucuronidase (K01195) was higher in female IL-10 KO mice than that in female WT mice by PICRUSt.

Conclusions: Our results suggest that microbiota-host interactions might differ between sexes during development of IBD.

Keywords: Gut microbiota; Inflammatory bowel disease; Interleukin-10; Sequence analysis; Sex differences.

Copyright © 2019 Korean Society of Cancer Prevention.

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Conflict of interest statement

CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

Figures

Figure 1

Figure 1

Diversity indices of gut microbiota. Microbiota richness: (A) operational taxonomic unit [OTU] counts and (B) Accumulated Cyclone Energy [ACE]; and diversity: (C) Shannon (D) phylogenic diversity) in wild type (WT) mice and interleukin 10 (IL-10) knockout (KO) mice of both sexes. (A–D) _P_-value of Kruskal–Wallis < 0.05 for. Beta diversity analyses of Principal coordinates plot (E) and Unweighted Pair Group Method with Arithmetic mean tree demonstrate that samples are clustered into distinct groups by sex and genotypes (F). *P < 0.013, **P < 0.0025 after Holm–Bonferroni correction.

Figure 2

Figure 2

Gut microbiota composition at (A) phylum level and (B) family level in male and female mice of wild type (WT) groups and inter-leukin 10 (IL-10) knockout (KO) groups. *P < 0.013 for male vs. female either in WT groups or IL-10 KO groups, #P < 0.013 for WT vs. IL-10 KO either in male or female groups after Holm–Bonferroni correction.

Figure 3

Figure 3

Relative abundance of specific taxa. Firmicutes to Bacteroides ratio (A) and relative abundance in major phylum (B–D) and family taxa (E–H). WT, wild type; IL-10, interleulin 10; KO, knockout. Kruskal–Wallis P < 0.05 for (A–H). *P < 0.013, **P < 0.0025 after Holm–Bonferroni correction.

Figure 4

Figure 4

Linear discriminant analysis (LDA) effect size analyses. (A) Male wild type (WT) mice and female WT mice, (B) male WT mice and male interleulin 10 (IL-10) knockout (KO) mice, and (C) female WT mice and female IL-10 KO mice. Only top ten and bottom ten taxa were presented.

Figure 5

Figure 5

(A–D) Representative species increased in interleulin 10 (IL-10) knockout (KO) mice. (E) Bacteroides vulgatus increased in female mice. (F) Relative abundance of the Kyoto Encyclopedia of Genes and Genomes gene “beta-glucuronidaes” which is predicted by phylogenetic investigation of communities by reconstruction of unobserved states. WT, wild type. Kruskal–Wallis P < 0.05 for (A–F). *P < 0.013, **P < 0.0025 after Holm–Bonferroni correction.

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