Sa597 DIETARY-INDUCED BIOTIN DEFICIENCY AND TAMOXIFEN-INDUCED, INTESTINE-SPECIFIC DELETION OF THE BIOTIN TRANSPORTER IN ADULT MICE LEAD TO GUT MICROBIOME PERTURBATIONS

2021 ◽  
Vol 160 (6) ◽  
pp. S-567
Author(s):  
Julianne C. Yang ◽  
Subrata Sabui ◽  
Jonathan Skupsky Jonathan P. Jacobs ◽  
Hamid M. Said
Keyword(s):  
Gut Microbiome ◽  
Biotin Deficiency ◽  
Adult Mice ◽  
Specific Deletion

scholarly journals Pancreatic islet beta cell-specific deletion of G6pc2 reduces fasting blood glucose

2020 ◽  
Vol 64 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Karin J Bosma ◽  
Mohsin Rahim ◽  
Kritika Singh ◽  
Slavina B Goleva ◽  
Martha L Wall ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Beta Cell ◽  
Fasting Blood Glucose ◽  
Human Islets ◽  
Peripheral Tissues ◽  
Adult Mice ◽  
Mouse Islets ◽  
Glucose Stimulated Insulin Secretion ◽  
Pancreatic Islet Beta Cell ◽  
Specific Deletion

The G6PC1, G6PC2 and G6PC3 genes encode distinct glucose-6-phosphatase catalytic subunit (G6PC) isoforms. In mice, germline deletion of G6pc2 lowers fasting blood glucose (FBG) without affecting fasting plasma insulin (FPI) while, in isolated islets, glucose-6-phosphatase activity and glucose cycling are abolished and glucose-stimulated insulin secretion (GSIS) is enhanced at submaximal but not high glucose. These observations are all consistent with a model in which G6PC2 regulates the sensitivity of GSIS to glucose by opposing the action of glucokinase. G6PC2 is highly expressed in human and mouse islet beta cells however, various studies have shown trace G6PC2 expression in multiple tissues raising the possibility that G6PC2 also affects FBG through non-islet cell actions. Using real-time PCR we show here that expression of G6pc1 and/or G6pc3 are much greater than G6pc2 in peripheral tissues, whereas G6pc2 expression is much higher than G6pc3 in both pancreas and islets with G6pc1 expression not detected. In adult mice, beta cell-specific deletion of G6pc2 was sufficient to reduce FBG without changing FPI. In addition, electronic health record-derived phenotype analyses showed no association between G6PC2 expression and phenotypes clearly unrelated to islet function in humans. Finally, we show that germline G6pc2 deletion enhances glycolysis in mouse islets and that glucose cycling can also be detected in human islets. These observations are all consistent with a mechanism by which G6PC2 action in islets is sufficient to regulate the sensitivity of GSIS to glucose and hence influence FBG without affecting FPI.

scholarly journals PO-128 Effects of 30%, 50%, 70%VO2 max treadmill exercises on gut microbiome of atherosclerotic mice

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Wenting Shi ◽  
Jin Li ◽  
Pengyi Zhang
Keyword(s):  
Gut Microbiome ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Exercise Group ◽  
High Fat ◽  
Vo2 Max ◽  
Adult Mice ◽  
Medium Intensity ◽  
Before And After ◽  
Low Intensity Exercise

Objective  To observe the dynamic changes of gut microbiome in mice before and after different intensities of treadmill exercises, and to explore the effects of different intensities of treadmill exercises on gut microbiome of atherosclerotic (AS) mice. Methods  The 50 male ApoE-/- mice aged 8 weeks were randomly divided into 2 groups, 10 mice in the general feeding group and the other 40 mice in the AS group, which were fed with normal and high-fat diet for 4 weeks respectively. Weight and blood test were taken before and after 4 weeks feeding. The serum Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL) levels were examined by blood test in ApoE-/- mice model, and atherosclerotic disease degeneration score of adult mice was used to determine the success of modeling after 4 weeks feeding. Then two mice selected from the normal and high-fat group respectively selected to test the maximum oxygen uptake (VO2 max) by the reformative Bedford method, and the running platform speed and slope corresponding to 30%, 50% and 70%VO2 max were determined. The 40 AS mice were randomly divided into the model blank group, the low-intensity exercise group, the medium-intensity exercise group and the high-intensity exercise group according to their weight for 4 weeks of exercises, respectively. The low-intensity exercise group was 30% VO2 max, with a slope of 10 degrees and a speed of 10 m/min. The medium intensity exercise group was 50% VO2 max with a slope of 10 degrees and a speed of 15 m/min. The high-intensity exercise group was 70% VO2 max with a slope of 10 degrees and a speed of 20 m/min. The exercises were performed for 4 weeks, 5 days a week, 20 minutes a day. The fresh feces were collected from 5 groups of mice before and after 4 weeks treadmill exercises. The number of gut Lactobacillus, Bacteroides, Firmicutes, Bifidobacterium, Verrucomicrobiaceae, Akkermansia , Escherichia coli, Collinsella and Clostridium in AS mice were analyzed by 16s sequencing.  Results 1. The TG, TC and LDL-C were significantly increased in the blood serum of the mice after the modeling, and the HDL-C was decreased, and the atherosclerotic disease degeneration score was significantly increased in the adult mice, and the modeling was successful. 2. The different intensity treadmill exercises can increase the number of gut probiotics in mice and decrease the number of harmful bacteria. The beneficial bacteria in gut tract of AS mice with moderate intensity of 50% VO2max was observed in the experiment: Bacteroides, Bifidobacterium and Verrucomicrobiaceae, Akkermansia were significantly increased, P<0.05. The harmful bacteria:Lactobacillus, Escherichia coli, Collinsella and Clostridium were significantly decreased, P<0.05. The ratio of Firmicutes / Bacteroidetes was increased. Conclusions  1. High-fat diet can lead to AS in ApoE-/- mice. 2. The different intensity treadmill exercises can reduce the weight of AS mice. 3. The number and abundance of probiotics of gut microbiome of AS mice could be promoted by different intensity treadmill exercises, among which the medium intensity aerobic exercise can significantly increase the number of beneficial bacteria such Bacteroidetes, Bifidobacteria, Verrucomicrobiaceae and Akkermansia, meanwhile, the structure of gut microbiome in AS mice was improved as well.

scholarly journals Citrus reticulatae pericarpium Extract Decreases the Susceptibility to HFD-Induced Glycolipid Metabolism Disorder in Mice Exposed to Azithromycin in Early Life

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanqi Lu ◽  
Yanting You ◽  
Xinghong Zhou ◽  
Qiuxing He ◽  
Ming Wang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
High Fat Diet ◽  
Early Life ◽  
Underlying Mechanism ◽  
Inflammatory Factors ◽  
Glycolipid Metabolism ◽  
Metabolism Disorder ◽  
Adult Mice ◽  
Gut Microbe ◽  
Old Mice

BackgroundStudies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process.PurposeThe study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated.Methods and ResultsThree-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects.ConclusionTaken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.

scholarly journals Endothelial Unc5B controls blood-brain barrier integrity

2021 ◽  
Author(s):  
Kevin Boyé ◽  
Luiz Henrique Medeiros Geraldo ◽  
Jessica furtado ◽  
Laurence Pibouin-fragner ◽  
Mathilde Poulet ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Proper Function ◽  
Downstream Signaling ◽  
Adult Mice ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Specific Deletion ◽  
Blood Brain Barrier Integrity ◽  
Bbb Opening

Blood-brain barrier (BBB) integrity is critical for proper function of the central nervous system (CNS). Here, we showed that the endothelial Netrin1 receptor Unc5B controls BBB integrity by maintaining Wnt/β-catenin signaling. Inducible endothelial-specific deletion of Unc5B in adult mice led to region and size-selective BBB opening. Loss of Unc5B decreased BBB Wnt/β-catenin signaling, and β-catenin overexpression rescued Unc5B mutant BBB defects. Mechanistically, Netrin1 enhanced Unc5B interaction with the Wnt co-receptor LRP6, induced its phosphorylation and activated Wnt/β-catenin downstream signaling. Intravenous delivery of antibodies blocking Netrin1 binding to Unc5B caused a transient disruption of Wnt signaling and BBB breakdown, followed by neurovascular barrier resealing. These data identify Netrin-Unc5B signaling as a novel regulator of BBB integrity with potential therapeutic utility for CNS diseases.

scholarly journals The aging mouse microbiome has obesogenic characteristics

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Dana Binyamin ◽  
Nir Werbner ◽  
Meital Nuriel-Ohayon ◽  
Atara Uzan ◽  
Hadar Mor ◽  
...  
Keyword(s):  
Body Composition ◽  
Gut Microbiome ◽  
Fat Body ◽  
Fecal Microbiota Transplantation ◽  
Magnetic Bead ◽  
Fecal Microbiota ◽  
Metabolic Parameters ◽  
Aged Mice ◽  
Adult Mice ◽  
High Insulin

Abstract Background During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice. Methods Fecal and blood samples from adult (n = 42, 100–300 days) and aging (n = 32, 550–750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin. Results We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces. Conclusions We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.

Maternal gut microbiome regulates immunity to RSV infection in offspring

2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Wendy Fonseca ◽  
Carrie-Anne Malinczak ◽  
Kei Fujimura ◽  
Danny Li ◽  
Kathryn McCauley ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Maternal Plasma ◽  
Metabolic Reprogramming ◽  
Mucus Production ◽  
Intrinsic Factors ◽  
Adult Mice ◽  
Immune Alterations ◽  
Rsv Infection ◽  
Maternal Supplementation ◽  
Syncytial Virus

Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell–mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.

scholarly journals Astrocyte-Specific Deletion of Sox2 Promotes Functional Recovery After Traumatic Brain Injury

2017 ◽  
Vol 29 (1) ◽  
pp. 54-69 ◽  
Author(s):  
Chunhai Chen ◽  
Xiaoling Zhong ◽  
Derek K Smith ◽  
Wenjiao Tai ◽  
Jianjing Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Recovery ◽  
Cell Activation ◽  
Adult Brain ◽  
Astrocyte Activation ◽  
Compensatory Response ◽  
Adult Mice ◽  
Specific Deletion

Abstract Injury to the adult brain induces activation of local astrocytes, which serves as a compensatory response that modulates tissue damage and recovery. However, the mechanism governing astrocyte activation during brain injury remains largely unknown. Here we provide in vivo evidence that SOX2, a transcription factor critical for stem cells and brain development, is also required for injury-induced activation of adult cortical astrocytes. Genome-wide chromatin immunoprecipitation-seq analysis of mouse cortical tissues reveals that SOX2 binds to regulatory regions of genes associated with signaling pathways that control glial cell activation, such as Nr2e1, Mmd2, Wnt7a, and Akt2. Astrocyte-specific deletion of Sox2 in adult mice greatly diminishes glial response to controlled cortical impact injury and, most unexpectedly, dampens injury-induced cortical loss and benefits behavioral recovery of mice after injury. Together, these results uncover an essential role of SOX2 in somatic cells under pathological conditions and indicate that SOX2-dependent astrocyte activation could be targeted for functional recovery after traumatic brain injury.

Sign in / Sign up

Export Citation Format

Share Document