Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan 14;19(1):10.
doi: 10.1186/s12876-019-0930-3.

Role of colonic microbiota in the pathogenesis of ulcerative colitis

Ling-Yan Pei  1   2 , Yu-Shi Ke  3 , Huan-Hu Zhao  1   2 , Lin Wang  4 , Chao Jia  1   2   5 , Wei-Zhi Liu  1   2 , Qian-Hui Fu  1   2 , Meng-Ni Shi  1   2 , Jian Cui  1   2 , Shu-Chun Li  6   7
Affiliations

Role of colonic microbiota in the pathogenesis of ulcerative colitis

Ling-Yan Pei et al. BMC Gastroenterol. .

Abstract

Background: Recent studies have found gut microbiota to be closely associated with onset and perpetuation of UC. Currently, studies about gut microbiota have mainly covered samples collected from the intestinal lumen. However, the luminal flora is only part of the gut microbiota. Studies of the changes in mucosal flora under pathological conditions have been lacking. In this study, we investigated the correlation between the onset of UC and flora changes in different intestinal layers.

Methods: The dextran sulfate sodium(DSS)-induced UC model was established by exposing mice to cycles of DSS. The luminal contents, an inner mucus layer, and outer mucus layer were harvested under sterile conditions. The samples were then analyzed using high-throughput sequencing of 16S rRNA V3 + V4 amplicons. The colonic microbiota composition and diversity were analyzed and compared using MetaStat, LefSe, multivariate analysis of variance, and spatial statistics.

Results: The DSS-induced UC mouse model was successfully established. The diversity of the microbiota from luminal content, the outer mucus layer, and inner mucus layer were significantly different in both control and UC model groups. The statistically different OTUs belonged to Lachnospiraceae and Ruminococcaceae families within the order Clostridiales were mainly localized to the outer mucus layer.

Conclusions: The alterations in flora composition and diversity mainly occurred in the colonic outer mucus layer. The change of flora in the colonic mucus layers is of great significance in the understanding of common features of gut flora in IBD and the understanding of the relationship between gut flora and disease progression.

Keywords: Intestinal microbiota; Microbiology; Ulcerative colitis.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The experimental protocols were performed after approval and in accordance with the guidelines set by the Ethical Committee of Minzu University of China (ERM: 201702).

Consent for publication

Not applicable.

Competing interests

The authors declare that there are no conflicts of interest to disclose.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Evaluation of DSS-induced UC mice model. a. DAI of the control and model groups. b. Body weight of control and model group. c. Histological examination of colon tissue of control mice. The tissue sample was observed with 4.5-fold (left) and 20-fold (right) magnification. d. Histological examination of colon tissue of UC model mice. The tissue sample was observed with 4.5-fold (left) and 20-fold (right) magnification. Colonic biopsy sections from control and model groups were counterstained with hematoxylin. DAI: Disease active index; UC: Ulcerative colitis
Fig. 2
Fig. 2
Diversity analysis of the microbiota. a. Comparison of the relative abundance of bacteria in three layers at genus level between groups. The microbial composition within the luminal content, inner layer and outer mucus layer of SPF mice was determined by 16S amplicon analysis. Representative bar graphs from control and model groups are shown. b. Comparison of alpha diversity index (good_coverage index) between groups. c. Comparison of luminal contents flora beta diversity index between groups (Unifrac weighted distance PCoA and Anosim analysis). d. Comparison of outer mucus layer flora beta diversity index between groups (Unifrac weighted distance PCoA and Anosim analysis). e. The comparison of inner mucus layer flora beta diversity index between groups (Unifrac weighted distance PCoA and Anosim analysis). Principle coordinates analysis (PCoA) on weighted UniFrac distances was performed on all operational taxonomic units. The closer the samples are to one another the more similar the bacterial diversity and richness are. P-values to determine the statistical significance of clustering were calculated using the Anosim method. *CC: the luminal content of control group. CO: the outer mucus layer of the control group. CI: the inner mucus layer of the control group. MC: the luminal content of the model group. MO: the outer mucus layer of the model group. MI: the inner mucus layer of the model group
Fig. 3
Fig. 3
Differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer of the flora of the control group. a. Venn diagram showed differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer flora in the control group. b. Ternary diagram showed the differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer flora in the control group; c. The distribution histogram in LDA value showed the differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer flora of control group. LDA bar graphs of taxa/clades that are differentially abundant in the luminal content (red), inner layer (green) and outer mucus layer (blue) of the control group. Taxa in this graph were both statistically significant(P < 0.05) and had an LDA Score > 2, considered a significant effect size *CC: the luminal content of control group. CO: the outer mucus layer of the control group. CI: the inner mucus layer of the control group.
Fig. 4
Fig. 4
Differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer flora of UC model group. a. Venn diagram shows the differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer flora of UC model group; b. Ternary diagram showed the differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer flora of UC model group; c. The distribution histogram in LDA value showed the differentially abundant bacteria in the luminal content flora, inner mucus layer flora, and outer mucus layer flora of UC model group. LDA bar graphs of taxa/clades that are differentially abundant in the luminal content (red), inner layer (green) and outer mucus layer (blue) of the model group. Taxa in this graph were both statistically significant(P < 0.05) and had an LDA Score > 2, considered a significant effect size. *MC: the luminal content of the model group. MO: the outer mucus layer of the model group. MI: the inner mucus layer of the model group
Fig. 5
Fig. 5
Differentially abundant bacteria among the flora of the luminal contents, an inner mucus layer, and outer mucus layer between control and UC model groups. a. The UPSET R analysis of the differentially abundant bacteria of luminal contents flora, inner mucus layer flora and outer mucus layer flora of control and model groups. b, c, d: From left to right, the distribution histogram in LDA value of luminal contents flora, inner mucus layer flora, and outer mucus layer flora, respectively. e. Multiple logistic regression analysis of the relationship between UC onset and the OTU abundance of each layer. f. The comparison of multiple logistic regression analysis of differentially abundant bacteria between two groups. *CC: the luminal content of control group. CO: the outer mucus layer of the control group. CI: the inner mucus layer of the control group. MC: the luminal content of the model group. MO: the outer mucus layer of the model group. MI: the inner mucus layer of the model group
See this image and copyright information in PMC

References

    1. Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, Kato J, Kobayashi K, Kobayashi K, Koganei K, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018;53(3):305–353. doi: 10.1007/s00535-018-1439-1. - DOI - PMC - PubMed
    1. Farrell RJ, Peppercorn MA: Ulcerative colitis. Lancet (London, England) 2002, 359(9303):331–340. - PubMed
    1. Seksik P, Sokol H, Lepage P, Vasquez N, Manichanh C, Mangin I, Pochart P, Dore J, Marteau P. Review article: the role of bacteria in onset and perpetuation of inflammatory bowel disease. Aliment Pharmacol Ther. 2006;24(Suppl 3):11–18. doi: 10.1111/j.1365-2036.2006.03053.x. - DOI - PubMed
    1. Teran-Ventura E, Aguilera M, Vergara P, Martinez V. Specific changes of gut commensal microbiota and TLRs during indomethacin-induced acute intestinal inflammation in rats. Journal of Crohn's & colitis. 2014;8(9):1043–1054. doi: 10.1016/j.crohns.2014.02.001. - DOI - PubMed
    1. Wang Y, Gao X, Ghozlane A, Hu H, Li X, Xiao Y, Li D, Yu G, Zhang T. Characteristics of fecal microbiota in pediatric Crohn's disease and their dynamic changes during infliximab therapy. Journal of Crohn's & colitis. 2017. - PubMed

Substances

LinkOut - more resources