ABSTRACT: Cell autonomous and non-autonomous interactions of a western-style diet and the vitamin D receptor in intestinal homeostasis and tumorigenesis
Project description:These data suggest that co-culture with macrophages increases expression of NDRG-1 in epithelial cell lines. The finding is confirmed in 1 mouse epithelial cell line, and in tissue derived from mice genetically and dietetically altered to increase macrophage infiltration of the small and large intestinal epithelium. NDRG1 is identified as a potential mediator of macrophage effects on tumorigenesis in the large and small intestine. Array data is part of a larger study involving the effects of Vitamin D, in concert with macrophages, on intestinal homeostasis and tumorigenesis, entitled Cell autonomous and non-autonomous interactions of a western-style diet and the vitamin D receptor in intestinal homeostasis and tumorigenesis Cells from human colon cancer cell lines were cultured either alone, with Vitamin D3, with THP1 macrophages, or with THP1 macrophages and Vitamin D3, in a system which allowed no physical contact but exchange of soluble factors between the cell types.
Project description:These data suggest that co-culture with macrophages increases expression of NDRG-1 in epithelial cell lines. The finding is confirmed in 1 mouse epithelial cell line, and in tissue derived from mice genetically and dietetically altered to increase macrophage infiltration of the small and large intestinal epithelium. NDRG1 is identified as a potential mediator of macrophage effects on tumorigenesis in the large and small intestine. Array data is part of a larger study involving the effects of Vitamin D, in concert with macrophages, on intestinal homeostasis and tumorigenesis, entitled Cell autonomous and non-autonomous interactions of a western-style diet and the vitamin D receptor in intestinal homeostasis and tumorigenesis
Project description:Western diet enhances intestinal tumorigenesis in Min/+ mice, associating with mucosal metabolic and inflammatory stress and loss of Apc heterozygosity We investigated the interaction of WD and heterozygous mutation in the Apc gene in the histologically normal intestinal mucosa of ApcMin/+ (Min/+) mice. AIN-93G diet vs. a diet modified from AIN-93G, with high fat and low fiber, vitamin D, calcium and folate. (66.4% of total fat from milk, and 33.6% from rapeseed and sunflower oil)
Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver
Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver Keywords: repeat sample
Project description:Obesity is associated with an increased risk of mucosal infections; however, the mechanistic basis of this phenomenon remains incompletely defined. Intestinal mucus barrier systems normally prevent infections, but are sensitive to changes in the luminal environment. Here we demonstrate that mice exposed to an obesogenic Western-style diet (WSD) suffer regiospecific failure of the mucus barrier in the small intestinal jejunum caused by diet-induced mucus condensation, which occurs independently of microbiota alterations. Mucus barrier disruption due to either WSD exposure or chromosomal Muc2 deletion results in collapse of the commensal jejunal microbiota, which in turn sensitises mice to atypical jejunal colonization by the enteric pathogen Citrobacter rodentium. We identify the jejunal mucus layer as a microbial habitat, and link the regiospecific mucus dependency of the microbiota to fundamental properties of the jejunal niche. Together, our data identifies a symbiotic mucus-microbiota relationship that normally prevents jejunal pathogen colonization, but is highly sensitive to disruption by exposure to a Western-style diet.
Project description:To investigate the effect of wetern-style diet on Paneth cells, we performed bulk RNAseq on sorted Paneth cells from mice fed for 3 months with western-style diet (NWD1) and control diet (AIN76A)
Project description:Little is known about how interactions between diet, intestinal stem cells (ISCs) and immune cells impact the early steps of intestinal tumorigenesis. Here, we show that a high fat diet (HFD) reduces the expression of the major histocompatibility complex II (MHC-II) genes in intestinal epithelial cells including ISCs. This decline in epithelial MHC-II expression in a HFD correlates with reduced diversity of the intestinal microbiome and is recapitulated in antibiotic treated and germ-free mice on a control diet. Mechanistically, pattern recognition receptor (PRR) and IFN g signaling regulate epithelial MHC-II expression where genetic ablation of these signaling pathways dampen MHC-II epithelial expression. Interestingly, upon loss of the tumor suppressor gene Apc in a HFD, MHC-II- ISCs harbor greater in vivo tumor-initiating capacity than their MHC-II+ counterparts when transplanted into immune-component hosts but not immune-deficient hosts, thus implicating a role for epithelial MHC-II-mediated immune surveillance in suppressing tumorigenesis. Finally, ISC-specific genetic ablation of MHC-II in engineered Apc-mediated intestinal tumor models increases tumor burden in a cell autonomous manner. These findings highlight how a HFD perturbs a microbiome – stem cell – immune cell crosstalk in the intestine and contributes to tumor initiation through the dampening of MHC-II expression in pre-malignant ISCs.
Project description:Lactobacillus plantarum is a common inhabitant of mammalian gastrointestinal tracts and specific strains belonging to this species are marketed as probiotics intended to confer beneficial health effects. To assist in determining the physiological status and host-microbe interactions of L. plantarum in the digestive tract we assessed changes in the transcriptome of L. plantarum WCFS1 during colonization of the cecum of germ-free mice. According to the transcript profiles L. plantarum WCFS1 was metabolically active and not under severe stress in this intestinal compartment. Carbohydrate metabolism was the most strongly affected functional gene category whereby many genes encoding diverse sugar transport and degradation pathways were induced in mice even compared to L. plantarum grown in a mouse chow-derived laboratory medium. This suggests that the ability of L. plantarum WCFS1 to consume diverse energy sources including plant-associated and host-derived carbohydrates was increased during its residence in the digestive tract. Many of these genes were also induced in L. plantarum colonizing germ-free mice fed a humanized Western-style diet. Similarly a core set of genes encoding cell surface-related properties were differentially expressed in mice. This set includes genes required for the D-alanylation and glycosylation of lipoteichoic acids that were strongly down-regulated in mice. In total L. plantarum exhibits a distinct in vivo transcriptome directed towards adaptation to the mouse intestinal environment. Keywords: cell type comparison Six-week old germ-free C57 Black-6 male mice were inoculated with a single dose of 109 CFU of exponential-phase L. plantarum WCFS1 cells. The mice were sacrificed 15 days later, after sufficient time had passed for several turnovers of the intestinal epithelium and its overlying mucosal layer. Four mice were fed on Chow diet and two mice were fed on western style diet. RNA was isolated from the cecum of these mice. The transcriptome of L. plantarum in these mice was compared to that of L. plantarum grown on MRS broth, Chow broth, or on chemically defined media with either glucose or lactose as carbon- and energy source.