Project description:Arecoline is an alkaloid extracted from betel nut, which has various pharmacological effects. In the present study, we showed that arecoline aggravated experimental acute ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) in mice. We measured body weight and colon length, evaluated disease activity index, colon pathology sections, and levels of colonic inflammatory factors. Arecoline exacerbated the clinical signs of UC and the colonic inflammatory response in mice. The results of 16S rRNA sequencing of fecal samples showed a significant decrease in the percentage of probiotic bacteria Ligilactobacillus, Limosilactobacillus and Lactobacillus and a significant increase in the percentage of conditionally pathogenic bacteria Odoribacter and Bacteroides after arecoline treatment. Serum untargeted metabolomics showed that arecoline intervention reduced the levels of ergothioneine, pentostatin, diadenosine tetraphosphate and other metabolites and modulated nicotinate and nicotinamide metabolism, metabolic pathways, glyoxylate and dicarboxylate metabolism, and other metabolic pathways of intestinal microorganisms. According to the combined microbial and metabolite analysis, arecoline influences metabolite levels by modulating the intestinal microbiota. In summary, it was found that arecoline treatment exacerbated colonic injury and intestinal inflammatory responses in UC mice, disrupted the host's intestinal flora, and affected changes in flora metabolites, thereby exacerbating the development of colonic inflammation. Therefore, the consumption of betel nut can be associated with the risk of aggravating UC.
Project description:Butyrate can modulate the immune response and energy expenditure of animals and enhance intestinal health. The present study investigated changes in the intestinal microbiota composition and serum metabolites of young broilers in response to 3,000 ppm butyrate in the form of butyrate glycerides (BG) via pyrosequencing of bacterial 16S rRNA genes and nuclear magnetic resonance (NMR). The dietary treatment did not affect the alpha diversity of intestinal microbiota, but altered its composition. Thirty-nine key operational taxonomic units (OTUs) in differentiating cecal microbiota community structures between BG treated and untreated chickens were also identified. Bifidobacterium was, in particular, affected by the dietary treatment significantly, showing an increase in not only the abundance (approximately 3 fold, P ≤ 0.05) but also the species diversity. The (NMR)-based analysis revealed an increase in serum concentrations of alanine, low-density and very low-density lipoproteins, and lipids (P ≤ 0.05) by BG. More interestingly, the dietary treatment also boosted (P ≤ 0.05) serum concentrations of bacterial metabolites, including choline, glycerophosphorylcholine, dimethylamine, trimethylamine, trimethylamine-N-oxide, lactate, and succinate. In conclusion, the data suggest the modulation of intestinal microbiota and serum metabolites by BG dietary treatment and potential contribution of intestinal bacteria to lipid metabolism/energy homeostasis in broilers.
Project description:In this study the gene expression differences between two titanium surfaces produced at Maastricht University were investigated. These two surfaces were: flat titanium-coated polystyrene and a titanium-coated polystyrene surface imprinted with a pattern selected from an earlier screening study (Ti1018). This pattern was selected based on the osteoinductive properties observed. As a positive control cells on the flat surface were treated with dexamethasone.
Project description:IntroductionAtopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual's appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.MethodsIn this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.ResultsThe levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.DiscussionThese findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.
Project description:Sterol Response Element Binding Protein 2 (SREBP2) transcription factor is a master regulator of cholesterol homeostasis. Treatment with statins, inhibitors of cholesterol synthesis, activates intestinal SREBP2, which may hinder their cholesterol-lowering effects. Overactivation of SREBP2 in mouse liver was shown to have no effect on plasma cholesterol. However, the influence of activating intestinal SREBP2 on plasma cholesterol is not known. We have generated a novel transgenic mouse model with intestine specific overexpression of active SREBP2 (ISR2) driven by villin promoter. ISR2 mice showed overexpression of active SREBP2 specifically in the intestine. Microarray analysis of jejunal RNA from ISR2 mice showed a significant increase in genes involved in fatty acid and cholesterol synthesis. Cholesterol and triglyceride (TG) in jejunum and liver (mg/g protein) were significantly increased in ISR2 vs wild type mice. Serum Cholesterol was significantly increased in VLDL and LDL fractions whereas the level of serum triglycerides was decreased in ISR2 vs wild type mice. In conclusion, activation of intestinal SREBP2 alone seems to be sufficient to increase plasma cholesterol, highlighting the essential role of intestine in maintaining cholesterol homeostasis in the body.
Project description:Amomum tsao-ko, as an edible and medicinal variety, has been cultivated for more than 600 years in China. Recently, two cultivars, A. tsao-ko and Amomum paratsao-ko, were found in A. tsao-ko planting area. The two cultivars are often confused because of the similar phenotype and difficult to distinguish through sensory judgment. In this study, the non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics combined with near-infrared spectroscopy (NIRS) were used for dissecting the two cultivars with phenotypic differences. According to principal component analysis (PCA) loading diagram and orthogonal partial least squares discriminant analysis (OPLS-DA) S-plot of the metabolites, the accumulation of major components including 1,8-cineole, α-phellandrene, (E)-2-decenal, (-)-β-pinene, (E)-2-octenal, 1-octanal, D-limonene, and decanal, were present differences between the two cultivars. Seven metabolites potential differentiated biomarkers as β-selinene, decamethylcyclopentasiloxane, (E,Z)-2,6-dodecadienal, (E)-2-hexenal, (E)-2-decenal, isogeranial, 1,8-cineole and β-cubebene were determined. Although A. tsao-ko and A. paratsao-ko belong to the same genera and are similar in plant and fruit morphology, the composition and content of the main components were exposed significant discrepancy, so it is necessary to distinguish them. In this study, the discriminant model established by GC-MS or NIRS combined with multivariate analysis has achieved a good classification effect. NIRS has the advantages of simple, fast and nondestructive and can be used for rapid identification of varieties and fruit tissues.
Project description:Fragile X syndrome (FXS) is a neurodevelopmental disorder oftentimes associated with abnormal social behaviors and altered sensory responsiveness. It is hypothesized that the inappropriate filtering of sensory stimuli, including olfaction, can lead to aberrant social behavior in FXS. However, previous studies investigating olfaction in animal models of FXS have shown inconsistent results. Here, we found that Fmr1 knock-out (KO) mice, a mouse model of FXS, showed increased sniffing duration for non-social odors during their first exposure. Additionally, while wild-type (WT) males demonstrated differences in behavioral patterns between non-social odors while Fmr1 KO males did not show such distinction. We also showed that Fmr1 KO males spent significantly less time sniffing female urine odor compared to WT males. Moreover, we found an increased volume of the olfactory bulb in Fmr1 KO males. Overall, our findings suggest that the Fmr1 KO mice demonstrate atypical olfactory behaviors as well as structural changes in the olfactory bulb.
Project description:BackgroundCoffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development.MethodsWe measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort (n = 29 133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes.ResultsOverall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% confidence interval [CI] = 2.00 to 7.74) for tyrosine to 4.95 (95% CI = 2.64 to 9.29) for GCA and from 4.00 (95% CI = 2.42 to 6.62) for GCA to 6.77 (95% CI = 3.62 to 12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; odds ratio ranged from 0.16 to 0.37. Associations persisted following diet adjustment and for outcomes occurring greater than 10 years after blood collection.ConclusionsA broad range of compounds were associated with coffee drinking, incident liver cancer, and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee.
Project description:Lactulose is a common component in foods. However, the effect of lactulose on intestinal flora and overall metabolic levels remains unclear. Therefore, this study aims to explore the regulative role of lactulose on intestinal flora and serum metabolites via in vitro simulated colonic fermentation model and in vivo colitis mouse model. The results showed that lactulose significantly enriched beneficial bacteria including Dubosiella and Bifidobacterium, and reduced pathogenic bacteria such as Fusobacterium. Moreover, lactulose significantly inhibited dextran sodium sulfate-induced body weight loss, colon shortening, colonic inflammatory infiltration, and pro-inflammatory cytokines IL-6, TNF-α, IL-17, and IL-1β. Lactulose significantly affected serum metabolome in colitis mice and total 24 metabolites representing a high inter-group difference were obtained. Correlation analysis revealed that the changes in serum metabolites were closely associated with the role of intestinal flora, and thus affected phenotypic indicators. Our study provides a reference for nutritional characteristics and application scenarios of dietary lactulose.
Project description:H3K4me1 (ab8895 Abcam) and H3K27ac (ab4729 Abcam) antibodies were used for ChIP-seq in Ring1a-/- mouse ES cells and after 48h tamoxifen treatment in conditional knock-out of Ring1b in the Ring1a -/- background.