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The Dynamic Changes of Gut Microbiota in Muc2 Deficient Mice.

ABSTRACT: Gut dysbiosis is associated with colitis-associated colorectal carcinogenesis, and the genetic deficiency of the Muc2 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 Muc2^-/- mice are unclear. Muc2^-/- and Muc2^+/+ mice were generated by backcrossing from Muc2^+/- 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, Muc2^-/- 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-? (TNF-?), interleukin 1 ? (IL-1?), i-kappa-B-kinase ? (IKK?)) were significantly increased in colonic epithelial cells of Muc2^-/- mice. In general, structural segregation of gut microbiota was observed throughout the experimental time points between the Muc2^-/- and Muc2^+/+ mice. Impressively, in Muc2^-/- mice, Alpha diversities reflected by Shannon and Chao indexes were higher, the phylum of Firmicutes was enriched and Bacteroidetes was decreased, and Desulfovibrio, Escherichia, Akkermansia, Turicibacter, and Erysipelotrichaceae were significantly increased, but Lactobacilli and Lachnospiraceae were significantly decreased. Moreover, the abundance of Ruminococcaceae and butyrate-producing bacteria was significantly higher in the Muc2^-/- mice. There were significant differences of gut microbiota between Muc2^-/- and Muc2^+/+ 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.

SUBMITTER: Wu M

PROVIDER: S-EPMC6164417 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The Dynamic Changes of Gut Microbiota in Muc2 Deficient Mice.

Wu Minna M Wu Yaqi Y Li Jianmin J Bao Yonghua Y Guo Yongchen Y Yang Wancai W

International journal of molecular sciences 20180918 9

Gut dysbiosis is associated with colitis-associated colorectal carcinogenesis, and the genetic deficiency of the Muc2 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 Muc2-/- mice are unclear. Muc2-/- and Muc2+/+ mice were generated by backcrossing from Muc2+/- mice, and the feca ...[more]

PMID: 30231491

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Project description:Gut microbiota dysbiosis, together with goblet cells dysfunction has been observed in ulcerative colitis cases. This study aims to evaluate the potential of 2'-fucosyllactose (2'-FL) supplementation in inhibiting intestinal inflammation through regulating gut microbiota, protecting goblet cells, and stimulating mucin secretion. 2'-FL was orally administered to C57BL/6J mice daily (400 mg/kg bw) for 21 days and 5% dextran sulfate sodium (DSS) was used to induce the colitis in the last 7 days. Meanwhile, fecal microbiota transplantation (FMT) was conducted to test the roles of gut microbiota in the remission of colitis by 2'-FL. Gut microbiota alteration was analyzed through 16S ribosomal RNA (16S rRNA) sequencing. Periodic acid-Schiff (PAS), immunofluorescence staining, as well as mucin 2 (MUC2) and NOD-like receptor family pyrin domain containing 6 (NLRP6) messenger RNA (mRNA) expression in colon fragments was performed and detected. The results showed that the DSS + 2'-FL mice were found to have a slower rate of weight loss, lower disease activity index (DAI) scores, and longer colon lengths than the DSS group (p < 0.05), so in the FMT recipient mice which received fecal microbiota from the DSS + 2'-FL group. In addition, the data revealed that 2'-FL relieved the disorder of DSS-induced gut microbiota, including decreasing the high abundance of mucin-utilizing bacteria in the DSS group, such as Bacteroides, Lachnospiraceae NK4A136, Lachnospiraceae, and Bacteroides vulgatus. PAS and immunofluorescence staining showed that 2'-FL treatment promoted the recovery of goblet cells and enhanced MUC2 and NLRP6 expression, which was also observed in the FM (DSS + 2'-FL) group. Moreover, NLRP6, which has been proved to be a negative regulator for Toll-like receptor 4/myeloid differential protein-8/nuclear factor-kappa B (TLR4/MyD88/NF-κB) pathway, was upregulated by 2'-FL in colon tissue. In conclusion, this study suggests that 2'-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism associates with the recovery of goblet cells number and improves MUC2 secretion through TLR4-related pathway.

Project description:The gut microbiota plays a key role in the pathogenesis of diseases affecting preterm infants and gestational age is one of the important factors which affect the gut microbiota of infants. To determine the characteristics of the gut microbiota in preterm infants of different gestational ages from birth to 1 year after birth, we collected 622 fecal samples from neonates of different gestational ages at different time points after birth. According to the gestational ages, the samples were divided into four groups, extremely preterm, very preterm, moderate to late preterm, and term group. Meconium and fecal samples at day 14, 28, 120, and 365 after birth were collected. 16S rRNA sequencing was performed and the composition and structure of the gut microbiota in preterm infants of different gestational age was compared with that of term infants. In our study, alpha diversity of meconium in extremely preterm group was higher than very preterm group, moderate to late preterm group and term group and alpha diversity of meconium in preterm group was decreased with increasing of gestational age. At day 14 to day 120 after birth, alpha diversity of term and moderate to late preterm group were significantly higher than other two preterm groups. However, moderate to late preterm group owned the highest alpha diversity which was higher than term group at day 365 after birth. Besides, the results shown the duration of opportunistic pathogen such as Klebsiella and Enterococcus which dominant colonization was different in different gestational age groups. As well as the probiotics, such as Bifidobacterium, which abundance enriched at different time point in different gestational age groups. We profiled the features of dynamic changes of gut microbiome from different gestational ages infants. The results of our research provide new insights for individualized interventions of specific microbes of preterm infants with different gestational ages at different time points after birth.

Dataset Information

The Dynamic Changes of Gut Microbiota in Muc2 Deficient Mice.

Publications

The Dynamic Changes of Gut Microbiota in <i>Muc2</i> Deficient Mice.

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