Project description:Milk and soy are reported to contain bioactive molecules with antibacterial and immunomodulatory actions, which may be beneficial to people with IBD. The aim of this study was to determine whether diets containing ruminant milk or soy solids reduce intestinal inflammation in Il10-/- mice. Male Il10-/- mice and C57BL/6J mice were fed diets containing 40% (w/w) sheep, goat, or cow whole milk powder, 40% (w/w) soy solids (NOW® Foods Soy Milk Powder, Instant), or one of two control diets (casein-free modified-AIN76A or standard AIN76A) from 4 to 11 weeks of age. Diets were based on AIN76A, which was included as an inter-experimental control for inflammation. For all diets except AIN76A, total protein, fat, carbohydrate and energy were kept as similar as possible. Weight and food intake were measured throughout the experiment (three times weekly), and intestinal tissue was taken for histopathology evaluation of inflammation and analysis of gene expression. Analysis of mouse weight and feed intake both showed a significant strain-diet interaction: Il10-/- mice fed the cow and goat milk diets ate less and gained less weight than all the other diet groups. This diet effect was not evident for the C57BL/6J mice. Il10-/- mice on the cow and goat milk diets had reduced colon histological injury scores relative to those on the other diets. Il10-/- mice on the cow and goat milk diets also had reduced expression of many immune/inflammatory-related genes and pathways.
Project description:The majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. One concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals genistein and daidzein which are normally present in soy beans. In the current study, we used a piglet model to look at this question. Piglets were either fed breast milk from the sow or were fed two different infant formulas (cow's milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food. Blood glucose and lipids were measured. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver.Microarray analysis was carried out to see if changes in liver gene expression could explain these effects of formula feeding. It was found that overall gene expression profiles were influenced by formula feeding compared to breast fed neonates. Gender-independent and unique effects of formula influenced cholesterol and iron metabolism. Further, soy formula feeding in comparison to milk-based formula failed to reveal any estrogenic actions on hepatic gene expression in either male or female pigs. Piglets (female, male) were either fed breast milk from the sow or were fed two different infant formulas (cow's milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food.
Project description:The majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. One concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals – genistein and daidzein which are normally present in soy beans. In the current study, we used a piglet model to look at this question. Piglets were either fed breast milk from the sow or were fed two different infant formulas (cow’s milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food. Blood glucose and lipids were measured. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver.Microarray analysis was carried out to see if changes in liver gene expression could explain these effects of formula feeding. It was found that overall gene expression profiles were influenced by formula feeding compared to breast fed neonates. Gender-independent and unique effects of formula influenced cholesterol and iron metabolism. Further, soy formula feeding in comparison to milk-based formula failed to reveal any estrogenic actions on hepatic gene expression in either male or female pigs.
Project description:Lcn2 is involved in host defense against pathogens, but the function in intestinal mucosal immunity and inflammation remains largely unknown. Genetic ablation of Lcn2 results in early-onset colitis and spontaneous emergence of right-sided colonic tumors in the setting of IL-10 deficiency (Lcn2-/-;IL10-/- mice). To address whether inflammation or other mechanisms drives the site-specific tumor locations gene expression analyses in proximal versus distal colons of Lcn2-/- IL10-/- mice were performed. Differential expression between distal colon versus cecum and proximal colon samples were analyses using Affymetrix MoGene 2.0 ST arrays on formalin-fixed, paraffin-embedded tissue sections of Lcn2-/-; IL10-/-mice.
Project description:The perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice. Given the frequent correlation between functional changes and transcriptional changes, we investigated the effect of diet (soy- vs. milk-based) on cardiac gene expression and how it relates to the additional factors of sex and disease. We found that gene expression in the heart is altered more by diet than by sex or an inherited disease. We also found that the healthy male heart may be sensitized to dietary perturbations of gene expression in that it displays a gene expression profile more similar to diseased hearts than to healthy female hearts. These observations may in part account for divergence in HCM phenotypes between males and females and between diets. Hearts from male and female wild-type or HCM C57BL/6 mice fed either a soy or casein-based diet were excised at 2 months of age. Total RNA was extracted from left ventricles. Biotin-labeled amplified RNA was hybridized to MG_U74Av2 Affymetrix microarrays.
Project description:The perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice. Given the frequent correlation between functional changes and transcriptional changes, we investigated the effect of diet (soy- vs. milk-based) on cardiac gene expression and how it relates to the additional factors of sex and disease. We found that gene expression in the heart is altered more by diet than by sex or an inherited disease. We also found that the healthy male heart may be sensitized to dietary perturbations of gene expression in that it displays a gene expression profile more similar to diseased hearts than to healthy female hearts. These observations may in part account for divergence in HCM phenotypes between males and females and between diets.
Project description:Epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are involved in the initiation and maintenance of intestinal inflammation. LMD is a technique that allows the extraction of specific cell types, such as colonic epithelial cells, to analyse gene expression. LMD of colon epithelial cells followed by microarray analysis could be of more value than microarray analysis of intact colon for determining which pathways are active in the colon mucosa in the early and late stages of inflammation due to increased sensitivity to changes in specific cell populations. An experiment was performed using microarray analysis of intact colon samples and microdissected colon epithelial cell samples from Il10-/- and C57BL/6J mice at 6 and 12 weeks of age to study the molecular changes that occur in early and late inflammation stages in colon epithelium of a mouse model of colitis. Results showed that intact colon and colon epithelial cell gene expression profiles were similar in terms of pathways between Il10-/- and C57BL/6J mice at 12 weeks of age and between Il10-/- mice at 12 and 6 weeks of age. More immune-related pathways were identified at 6 weeks of age in epithelial cells than intact colon. This suggests that LMD and targeting of specific cell types may be of particular use when studying the early stages of inflammation before the intestinal morphology is detectably altered, by increasing analysis sensitivity to mucosal gene expression changes. 2x2 factorial with two tissue types analysed. Two strains of mouse (Il10 knockout mouse and the background strain C57BL/6J) were sampled at 2 timepoints (6 and 12 weeks of age) and intact proximal colon and colon epithelium harvested from each mouse (6 mice per group except for group colon epithelium C57 mouse 12 weeks where only 5 samples reached quality control standards).
Project description:Soy-based diets have triggered the interest of the research community due to their beneficial effects on a wide variety of pathologies like breast and prostate cancer, diabetes, and atherosclerosis. However, the molecular details underlying these effects are far from being completely understood and several recent attempts have been made to elucidate the soy-induced liver transcriptome changes in different animal models. Here we used Next Generation Sequencing to identify a set of two microRNAs specifically modulated by short-term soy-enriched diet in young male mice and estimate their impact on the liver transcriptome assessed by microarray. Clustering and topological community detection (CTCD) network analysis of STRING generated interactions of transcriptome data led to the identification of five topological communities of genes characteristically altered and putatively targeted by microRNAs upon soy diet intervention.
Project description:Soy-based diets have triggered the interest of the research community due to their beneficial effects on a wide variety of pathologies like breast and prostate cancer, diabetes, and atherosclerosis. However, the molecular details underlying these effects are far from being completely understood and several recent attempts have been made to elucidate the soy-induced liver transcriptome changes in different animal models. Here we used Next Generation Sequencing to identify a set of two microRNAs specifically modulated by short-term soy-enriched diet in young male mice and estimate their impact on the liver transcriptome assessed by microarray. Clustering and topological community detection (CTCD) network analysis of STRING generated interactions of transcriptome data led to the identification of five topological communities of genes characteristically altered and putatively targeted by microRNAs upon soy diet intervention.
Project description:That commensal bacteria can influence intestinal inflammation has been observed using other models of chronic colitis. Loss of IL-10, a major immunosuppressive cytokine, induces spontaneous colitis in mice. The incidence of spontaneous polyp formation in IL-10-deficient mice was also completely eliminated in the absence of STING We used microarrays to evaluate the inflammatory cytokine expression in the colon from IL10 KO mice and IL10/STING KO mice.