Animal model of acute ulcerative colitis: Focus on the microbiome

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ISBN: 978-80-972360-8-3
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Animal model of acute ulcerative colitis: Focus on the microbiome

Petra Adamkova1 , Petra Hradicka , Sona Gancarcikova2 , Vlasta Demeckova
1 Pavol Jozef Safarik University in Kosice, Faculty of Science, Institute of Biology and Ecology, Kosice, Slovakia
2 University of Veterinary Medicine and Pharmacy in Kosice, Department of Microbiology and Immunology, Kosice, Slovakia

Inflammatory bowel disease (IBD) is a term for two conditions Crohn’s disease and ulcerative colitis (UC) that are characterized by chronic non-infectious inflammation of the gastrointestinal tract. Recent data suggests that dysbiosis may play a pivotal role in the pathogenesis of these diseases. As microbiome-based therapeutics that modulate the gut ecology have been proposed as a novel strategy for preventing IBD, the aim of the presented study was to evaluate the dextran sulphate sodium (DSS) rat model mainly in terms of microbial shifts to confirm its suitability for dysbiosis study in IBD.

Sprague Dawley rats (male, n=22) (Velaz, Prague, Czech Republic) were divided into DSS (n=16) and the healthy control (C) (n=6) groups. Experimental colitis was induced in five-weeks old animals with 5% DSS (40 KD; TdB Consultancy AB, Uppsala, Sweden) dissolved in deionized water given ad libitum for 7 days. To evaluate the severity of colitis, a disease activity index (DAI) score was determined on a daily basis. DAI included weight loss, stool consistency, and haematochezia. Faecal samples were collected at three time-points: before induction of colitis, at the end of DSS administration and at the end of the experiment. The samples were placed in −80 ◦C freezer and subsequently processed for next generation sequencing (NGS) analysis (Novogene Europe, Cambridge, UK).

The DAI, calculated based on the percentage of body weight decrease, diarrhoea, and bloody faeces, increased from day three in DSS-treated rats with the peak on the day seven and eight. The DAI score remained close to 0 in the non-colitis control group during the whole experimental period (no diarrhoea or rectal bleeding was observed). The alpha diversity indices (ACE and Chao) showed a reduction of the species abundance after DSS administration (day 7; pACE=0.0001; pChao=0.002) and also at the end of experiment (day 13; pACE=0.0043; pChao=0.029) compared to the first collection time point (before DSS administration). ANOSIM analysis within the DSS group demonstrated significantly increased (R = 0.812) inter-group differences after 7 days of DSS administration and greater inter-group beta distance was also preserved at the end of experiment (R=0.823 for DSS2 compared to DSS3). The T-test bar plot showed that species Lactobacillus murinus (p=0.001), Bacteroides thetaiotaomicron (p<0.001), Escherichia coli (p=0.037), Clostridiales bacterium (p=0.034) and Lachnospiraceae bacterium 615 (p=0.003) were significantly increased in the DSS group, while uncultured Bacteroidales bacteria (p=0.002) and Dubosiella newyorkensis (p=0.016) were significantly decreased.

In conclusion, this study confirmed the advantages of a DSS colitis rat model, such as its simplicity and reproducibility. Also, it has been shown that this model is suitable for monitoring and evaluating microbial changes. Nevertheless, the observation that certain bacterial species in the gut microbiota are associated with UC raises the question of whether these organisms are the causal agents or a consequence of the disease. Therefore, further in vivo studies are needed to investigate possible triggers of the disease.


This work was funded by APVV-16-0176 and VEGA 1/0015/21. The study was approved by the State Veterinary and Food Administration of the Slovak Republic (license number Ro-1222-3/2020-220).