Selection strategy of dextran sulfate sodium-induced acute or chronic colitis mouse models based on gut microbial profile

Abstract

Background: Dextran sulfate sodium (DSS) replicates ulcerative colitis (UC)-like colitis in murine models. However, the microbial characteristics of DSS-triggered colitis require further clarification. To analyze the changes in gut microbiota associated with DSS-induced acute and chronic colitis.

Methods: Acute colitis was induced in mice by administering 3% DSS for 1 week in the drinking water, and chronic colitis was induced by supplementing drinking water with 2.5% DSS every other week for 5 weeks. Control groups received the same drinking water without DSS supplementation. The histopathological score and length of the colons, and disease activity index (DAI) were evaluated to confirm the presence of experimental colitis. Intestinal microbiota was profiled by 16S rDNA sequencing of cecal content.

Results: Mice with both acute and chronic DSS-triggered colitis had significantly higher DAI and colon histopathological scores in contrast to the control groups (P < 0.0001, P < 0.0001), and the colon was remarkably shortened (P < 0.0001, P < 0.0001). The gut microbiota α-diversity was partly downregulated in both acute and chronic colitis groups in contrast to their respective control groups (Pielou index P = 0.0022, P = 0.0649; Shannon index P = 0.0022, P = 0.0931). The reduction in the Pielou and Shannon indices were more obvious in mice with acute colitis (P = 0.0022, P = 0.0043). The relative abundance of Bacteroides and Turicibacter was increased (all P < 0.05), while that of Lachnospiraceae, Ruminococcaceae, Ruminiclostridium, Rikenella, Alistipes, Alloprevotella, and Butyricicoccus was significantly decreased after acute DSS induction (all P < 0.05). The relative abundance of Bacteroides, Akkermansia, Helicobacter, Parabacteroides, Erysipelatoclostridium, Turicibacter and Romboutsia was also markedly increased (all P < 0.05), and that of Lachnospiraceae_NK4A136_group, Alistipes, Enterorhabdus, Prevotellaceae_UCG-001, Butyricicoccus, Ruminiclostridium_6, Muribaculum, Ruminococcaceae_NK4A214_group, Family_XIII_UCG-001 and Flavonifractor was significantly decreased after chronic DSS induction (all P < 0.05).

Conclusion: DSS-induced acute and chronic colitis demonstrated similar symptoms and histopathological changes. The changes in the gut microbiota of the acute colitis model were closer to that observed in UC. The acute colitis model had greater abundance of SCFAs-producing bacteria and lower α-diversity compared to the chronic colitis model.

Keywords: Acute colitis; Chronic colitis; Dextran sulfate sodium; Gut microbiota.

Fig. 1

DSS significantly induced inflammation in the colons of mice. A, B Disease activity index (DAI) dynamics across each cohort. C Mouse colon lengths of each group. D Colon histopathologic score of each group of mice. E Colonic tissues stained with H&E (200x; 400x). Data is depicted in terms of individual means or the mean ± SD of each group derived from three experimental replicates. ****P < 0.0001

Fig. 2

DSS alters diversity of gut microbiota in mice models of colitis. A Pielou index. B Shannon index. α-diversity was derived using a combination of the species richness (species situation) and species evenness (distribution) using the Pielou and Shannon indices. C Gut microbiota relationships and distribution are characterized with a UPGMA clustering tree. Samples are represented by end branches. In general, samples belonging to similar groups were clustered into a large branch with different branches representing different groups. Distance is indicated by the vertical axis. Samples with similar structure of bacterial communities are located in the same branch. D NMDS (Non-metric Multi-Dimensional Scaling). NMDS representas a dimension reduction analysis established on distance ranking. It is superior to linear models (including PCA and PCoA) and more accurately translates the nonlinear structure of ecological data. The accuracy of the model is evaluated by the stress value. The smaller the stress value is, the more reliable the model is. Generally, the stress value less than 0.1 is better. **P < 0.01

Fig. 3

DSS alters dominant gut microbiota structures across different levels in mice with colitis. Stacked bar plot depicts the phylum (A) / family (B) / genus (C) / species (D) structure of gut microbiota in each group of mice

Fig. 4

DSS alters gut microbiota structure in acute and chronic colitis mice differently at the phylum and family levels. A DSS alters the microbial structure of acute colitis mice at the phylum level. B DSS alters the microbial structure of chronic colitis mice at the phylum level. C DSS alters the microbial structure of acute colitis mice at the family level. D DSS alters the microbial structure of chronic colitis mice at the family level

Fig. 5

DSS alters gut microbiota structure in acute and chronic colitis mice differently at the genus and species levels. A DSS alters the microbial structure of acute colitis mice at the genus level. B DSS alters the microbial structure of chronic colitis mice at the genus level. C DSS alters the microbial structure of acute colitis mice at the species level. D DSS alters the microbial structure of chronic colitis mice at the species level