The Dynamic Changes of Gut Microbiota in Muc2 Deficient Mice

• Published in: International journal of molecular sciences 2018-09, Vol.19 (9), p.2809
• Main Authors: Wu, Minna, Wu, Yaqi, Li, Jianmin, Bao, Yonghua, Guo, Yongchen, Yang, Wancai
• Format: Article
• Language: English
• Subjects: Age; Animals; Bacteria; Carcinogenesis; Carcinogenesis - genetics; Carcinogenesis - pathology; Carcinogens; Colitis; Colitis - complications; Colitis - genetics; Colitis - microbiology; Colitis - pathology; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - etiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - pathology; Cyclooxygenase-2; Cytokines; Digestive system; Dysbacteriosis; Dysbiosis - complications; Dysbiosis - genetics; Dysbiosis - microbiology; Dysbiosis - pathology; Epithelial cells; Gastrointestinal Microbiome; Gene Deletion; Hyperplasia; IL-1β; Inflammation; Inflammatory bowel disease; Interleukin 1; Interleukin 6; Intestinal microflora; Intestine; Lactobacilli; Male; Mice; Microbiota; MUC2 gene; mucin; Mucin-2 - genetics; Next-generation sequencing; Primers; rRNA 16S; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092809

Gut dysbiosis is associated with colitis-associated colorectal carcinogenesis, and the genetic deficiency of the gene causes spontaneous development of colitis and colorectal cancer. Whether there are changes of gut microbiota and a linkage between the changes of microbiota and intestinal pathology in mice are unclear. and mice were generated by backcrossing from mice, and the fecal samples were collected at different dates (48th, 98th, 118th, 138th, and 178th day). Gut microbiota were analyzed by high-throughput sequencing with the universal 16S rRNA primers (V3⁻V5 region). All mice were sacrificed at day 178 to collect colonic tissue and epithelial cells for the analysis of histopathology and inflammatory cytokines. On the 178th day, mice developed colorectal chronic colitis, hyperplasia, adenomas and adenocarcinomas, and inflammatory cytokines (e.g., cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin 1 β (IL-1β), i-kappa-B-kinase β (IKKβ)) were significantly increased in colonic epithelial cells of mice. In general, structural segregation of gut microbiota was observed throughout the experimental time points between the and mice. Impressively, in mice, Alpha diversities reflected by Shannon and Chao indexes were higher, the phylum of Firmicutes was enriched and Bacteroidetes was decreased, and , , , , and were significantly increased, but and were significantly decreased. Moreover, the abundance of and butyrate-producing bacteria was significantly higher in the mice. There were significant differences of gut microbiota between and mice. The dynamic changes of microbiota might contribute to the development of colitis and colitis-associated colorectal carcinogenesis. Therefore, this study revealed specific functional bacteria in the development of colitis and colitis-associated colorectal carcinogenesis, which will benefit the development of preventive and therapeutic strategies for chronic inflammation and its malignant transformation.