Effect of tumor necrosis factor-related apoptosis-inducing ligand gene knock-out on the gut microbiota in mice with dextran sodium sulphate induced colitis

Shuzi Zheng; Kaiyu Huang; Hao WU; Jing Cai; Fangpeng YE; Yi Jiang

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Effect of tumor necrosis factor-related apoptosis-inducing ligand gene knock-out on the gut microbiota in mice with dextran sodium sulphate induced colitis

VernacularTitle: 肿瘤坏死因子相关凋亡诱导配体基因敲除对葡聚糖硫酸钠诱导结肠炎小鼠肠道菌群的影响
Author: Shuzi ZHENG ¹ ; Kaiyu HUANG ¹ ; Hao WU ² ; Jing CAI ³ ; Fangpeng YE ⁴ ; Yi JIANG ²
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1. Department of Pediatric Gastroenterology, The Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University, Wenzhou 325000, China
2. Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China
3. Department of Gastroenterology, The Wenzhou Central Hospital, Wenzhou 325000, China
4. Department of Gastroenterology, Ruian People′s Hospital, Wenzhou 325200, China
Publication Type:Journal Article
Keywords: TNF-related apoptosis-inducing ligand; Intestinal microbiota; Experimental colitis; Mice, knockout
From: Chinese Journal of Digestion 2019;39(11):759-764
CountryChina
Language:Chinese
Abstract: Objective:To investigate the influence of tumor necrosis factor-related apoptosis-inducing ligant (TRAIL) deficiency on mice colitis and the gut microbiota composition by inclding the expermental colitis model in tumor necrosis factor-related apoptosis-inducing ligand gene knockout (TRAIL^-/-) mice.
Methods:C57BL/6 TRAIL^-/- mice and wild type (WT) mice were selected and assigned into TRAIL^-/- control group (eight mice), TRAIL^-/- colitis group (16 mice), WT control group (eight mice) and WT colitis group (16 mice). The mice of two colitis groups were oral administrated with 3.5% dextran sulphate sodium (DSS) in drinking water for seven consecutive days to induce experimental colitis model. The severity of colitis was evaluated by clinical appearance and histopathological examination. The colonic tissue samples of mice were collected and microbiota profile was analyzed by 16S rDNA sequencing method. USEARCH software and R language were used to analyze the difference of gut microbiota among TRAIL^-/- control group, TRAIL^-/- colitis group, WT control group and WT colitis group. T test and Mann-Whitney U test were used for statistical analysis.
Results:After modeling, the disease activity index (DAI) of WT colitis mice and TRAIL^-/- colitis mice both gradually increased over time. Furthermore, compared with colitis mice, TRAIL^-/- colitis mice developed body weight loss, diarrhea and hemafecia earlier. On the seventh day after modeling, the percentage of body weight loss of TRAIL^-/- colitis mice and WT colitis mice was (28.98±2.84)% and (17.87±3.70)%, respectively; and the difference was statistically significant (t=9.53, P<0.01). The length of colon of TRAIL^-/- colitis mice was shorter than that of WT colitis mice ((4.63±0.28) cm vs. (6.02±0.41) cm), and the difference was statistically significant (t=11.20, P<0.01). The DAI of TRAIL^-/- colitis mice was higher than that of WT colitis mice (3.00±0.00 vs. 2.32±0.05), and the difference was statistically significant (t=54.40, P<0.01). The histological score of TRAIL^-/- colitis mice was higher than that of WT colitis mice (6.19±0.25 vs. 3.87±0.22), and the difference was statistically significant (t=27.87, P<0.01). Under the microscope, colonic mucosal epithelial injury, crypt structure destruction and inflammatory cell infiltration were more obvious in TRAIL^-/- colitis mice than in WT colitis mice. The alpha diversity of colonic flora was more significant in TRAIL^-/- colitis group compared with that of WT colitis group. At the family level, the relative richness of Deferribacteraceae, Ruminococcaceae, Rikenellaceae, F16 and Paraprevotellaceae significantly increased in TRAIL^-/- colitis group, but the relative richness of Enterococcaceae obviously reduced ((19.839±19.991)% vs. (7.224±11.241)%, (3.564±2.543)% vs.(2.861±3.821)%, (0.123±0.066)% vs. (0.068±0.049)%, (0.032±0.033)% vs. (0.006±0.011)%, (0.153±0.098)% vs. (0.062±0.054)% and (0.013±0.027)% vs. (0.054±0.121)%, respectively; U=51, 69, 53, 35, 49 and 69, respectively; P<0.01 and 0.05, respectively). In addition, at the genus level the relative richness of Oscillospira, Mucispirillum and Cytophaga in TRAIL^-/- colitis group remarkably elevated, and the relative richness of Enterococcus significantly decreased ((2.363±2.147)% vs. (1.813±2.847)%, (19.839±19.991)% vs. (7.223±11.241)%, (0.104±0.153)% vs. (0.046±0.069)% and (0.076±0.049)% vs. (0.135±0.074)%, respectively; U=70, 51, 66 and 65, respectively; P <0.05 and 0.01, respectively).
Conclusion:TRAIL deficiency aggravate DSS-induced colitis, and increase the alpha diversity of colonic microbiota in colitis mice.