scholarly journals Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 373 ◽  
Author(s):  
Yingchun Han ◽  
Bryan Glueck ◽  
David Shapiro ◽  
Aaron Miller ◽  
Sanjoy Roychowdhury ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ethanol Exposure ◽  
Endothelial Barrier ◽  
Saline Control ◽  
Control Group ◽  
Liver Sinusoidal Endothelial Cells ◽  
Microbial Composition ◽  
Barrier Integrity ◽  
Synbiotic Supplementation ◽  
Binge Ethanol

Alcohol overconsumption disrupts the gut microbiota and intestinal barrier, which decreases the production of beneficial microbial metabolic byproducts and allows for translocation of pathogenic bacterial-derived byproducts into the portal-hepatic circulation. As ethanol is known to damage liver sinusoidal endothelial cells (LSEC), here we evaluated dietary supplementation with a previously studied synbiotic on gut microbial composition, and hepatocyte and LSEC integrity in mice exposed to ethanol. We tested a chronic-binge ethanol feeding mouse model in which C57BL/6 female mice were fed ethanol (5% vol/vol) for 10 days and provided a single ethanol gavage (5 g/kg body weight) on day 11, 6 h before euthanasia. An ethanol-treatment group also received oral supplementation daily with a synbiotic; and an ethanol-control group received saline. Control mice were pair-fed and isocalorically substituted maltose dextran for ethanol over the entire exposure period; they received a saline gavage daily. Ethanol exposure decreased gut microbial abundance and diversity. This was linked with diminished expression of adherens junction proteins in hepatocytes and dysregulated expression of receptors for advanced glycation end-products; and this coincided with reduced expression of endothelial barrier proteins. Synbiotic supplementation mitigated these effects. These results demonstrate synbiotic supplementation, as a means to modulate ethanol-induced gut dysbiosis, is effective in attenuating injury to hepatocyte and liver endothelial barrier integrity, highlighting a link between the gut microbiome and early stages of acute liver injury in ethanol-exposed mice.

scholarly journals A Designer Synbiotic Attenuates Chronic-Binge Ethanol-Induced Gut-Liver Injury in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 97 ◽  
Author(s):  
Sanjoy Roychowdhury ◽  
Bryan Glueck ◽  
Yingchun Han ◽  
Mahmoud Ali Mohammad ◽  
Gail A. M. Cresci
Keyword(s):  
Liver Injury ◽  
Tight Junction ◽  
Biological Effects ◽  
Proximal Colon ◽  
Ethanol Exposure ◽  
Saline Control ◽  
Hepatocyte Injury ◽  
Junction Protein ◽  
Synbiotic Supplementation ◽  
Binge Ethanol

Gut dysbiosis and altered short-chain fatty acids are associated with ethanol-induced liver injury. SCFA are fermentation byproducts of the gut microbiota known to have many beneficial biological effects. We tested if a designer synbiotic could protect against ethanol-induced gut-liver injury. C57BL/6 female mice were exposed to chronic-binge ethanol feeding consisting of ethanol (5% vol/vol) for 10 days, followed by a single gavage (5 g/kg body weight) 6 h before euthanasia. A group of mice also received oral supplementation daily with a designer synbiotic, and another group received fecal slurry (FS); control animals received saline. Control mice were isocalorically substituted maltose dextran for ethanol over the entire exposure period. Ethanol exposure reduced expression of tight junction proteins in the proximal colon and induced hepatocyte injury and steatosis. Synbiotic supplementation not only mitigated losses in tight junction protein expression, but also prevented ethanol-induced steatosis and hepatocyte injury. Ethanol exposure also increased hepatic inflammation and oxidative stress, which was also attenuated by synbiotic supplementation. Mice receiving FS were not protected from ethanol-induced liver injury or steatosis. Results were associated with luminal SCFA levels and SCFA transporter expression in the proximal colon and liver. These results indicate supplementation with a designer synbiotic is effective in attenuating chronic-binge ethanol-induced gut-liver injury and steatosis in mice, and highlight the beneficial effects of the gut microbial fermentation byproducts.

scholarly journals The Prophylactic Use of Bovine Colostrum in a Murine Model of TNBS-Induced Colitis

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 492 ◽  
Author(s):  
Laura Menchetti ◽  
Giulio Curone ◽  
Iulia Elena Filipescu ◽  
Olimpia Barbato ◽  
Leonardo Leonardi ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical Signs ◽  
Interleukin 10 ◽  
Bovine Colostrum ◽  
Saline Control ◽  
Control Group ◽  
Microbial Composition ◽  
Expression Levels ◽  
Pre Treatment ◽  
Prophylactic Use

This study investigated the effects of a short-term administration of bovine colostrum (BC) in a TNBS model of induced colitis. Colitis was induced by TNBS treatment after seven days of BC (BC group, n = 12) or saline (control group, n = 12) administration in mice. Clinical signs, histopathological characteristics, expression levels of Toll-like receptor 4 (TLR4), pro- and anti-inflammatory cytokines, and microbial composition were assessed. BC was well tolerated and did not induce any histological damage or clinical symptoms. After TNBS treatment, the BC group showed a reduction in body weight (BW) loss compared to Control (p < 0.05). Moreover, expression levels of TLR4 (p < 0.01), Interleukin-1β (IL-1β; p < 0.001), Interleukin-8 (IL-8; p < 0.001), and Interleukin-10 (IL-10; p < 0.001) were lower in mice administered with BC. Finally, Escherichia coli were higher (p < 0.05), while Enterococci (p < 0.001), Lactobacillus spp. (p < 0.001), and Bifidobacterium spp. (p < 0.05) were lower in Control than BC group. This study confirms that pre-treatment with BC modulates the expression of genes and the count of microbes involved in the etiopathogenesis of colitis.

Abstract 606: Antithrombin Nanoparticle Therapy Safely Restores Endothelial Barrier Integrity and Reduces Vessel Hypercoagulability in Atherosclerotic Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Rohun U Palekar ◽  
Andrew P Jallouk ◽  
Hua Pan ◽  
Samuel A Wickline
Keyword(s):  
Endothelial Barrier ◽  
Thrombin Inhibitor ◽  
Saline Control ◽  
Resonance Spectroscopy ◽  
Therapeutic Effects ◽  
Thrombotic Risk ◽  
Barrier Integrity ◽  
Vascular Barrier Integrity

Introduction: Thrombin plays a major role in regulating signaling pathways responsible for atherogenesis, hypercoagulability and plaque permeability. Herein, we report the therapeutic effects of perfluorocarbon core nanoparticles (PFC-NP) conjugated to the thrombin inhibitor D-phenylalanyl-L-prolyl-L-chloromethylketone (PPACK-NP) on vascular barrier integrity and hypercoagulability. Methods and Results: ApoE-/- mice were fed a Western diet for 4 months, and received 3 doses/week of saline or 1 ml/kg PPACK-NP for the final month of feeding. Endothelial barrier integrity was assessed by quantifying the ability of atherosclerotic aortas to take up circulating semipermeable PFC-NP (~250 nm diameter). Whole aortas (arch to iliacs) were excised after 2 hour in vivo exposure to PFC-NP and underwent fluorine magnetic resonance spectroscopy ( 19 F-MRS) to quantify plaque-permeating PFC-NP. 19 F-MRS data revealed a significant decrease in plaque permeability to PFC-NP after PPACK-NP treatment compared to saline control (0.081 ± 0.011 μl PFC-NP/g aorta, N = 5 vs. 0.122 ± 0.014 μl PFC-NP/g aorta, N = 8 for PPACK-NP treated vs. saline control, p = 0.027). To assess hypercoagulability, carotid artery injury was induced photochemically to measure the time to complete occlusion as an index of thrombotic risk. Occlusion times were significantly prolonged with PPACK-NP treatment compared to untreated mice (49.8 ± 6.7 min, N = 5 vs. 26.1 ± 4.6 min, N = 9 for PPACK-NP treated vs. saline control, p = 0.019), indicating a decrease in vessel hypercoagulability after therapeutic intervention. Furthermore, PPACK-NP treatment of human aortic endothelial cells in vitro abrogated thrombin-mediated activation of surface PAR-1 receptors as measured by flow cytometry, suggesting a potential dual role for PPACK-NP in the localized modulation of both thrombosis and PAR-1 signaling. Moreover, this sustained therapeutic benefit is obtained without systemic anticoagulation as all clotting parameters and bleeding times are completely normalized within 60 minutes after i.v. injection. Conclusion: Thrombin inhibition with PPACK-NP is effective in restoring vascular barrier integrity and reducing focal thrombotic risk within a single month without incurring bleeding risk.

scholarly journals Ultrafine particles altered gut microbial population and metabolic profiles in a sex-specific manner in an obese mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kundi Yang ◽  
Mengyang Xu ◽  
Jingyi Cao ◽  
Qi Zhu ◽  
Monica Rahman ◽  
...  
Keyword(s):  
Ultrafine Particles ◽  
Microbial Population ◽  
Phosphate Buffer Solution ◽  
Biodiesel Fuel ◽  
Control Group ◽  
Obese Mouse ◽  
Rrna Gene ◽  
Obese Mice ◽  
Microbial Composition ◽  
Increased Risk

AbstractEmerging evidence has highlighted the connection between exposure to air pollution and the increased risk of obesity, metabolic syndrome, and comorbidities. Given the recent interest in studying the effects of ultrafine particle (UFP) on the health of obese individuals, this study examined the effects of gastrointestinal UFP exposure on gut microbial composition and metabolic function using an in vivo murine model of obesity in both sexes. UFPs generated from light-duty diesel engine combustion of petrodiesel (B0) and a petrodiesel/biodiesel fuel blend (80:20 v/v, B20) were administered orally. Multi-omics approaches, including liquid chromatography–mass spectrometry (LC–MS) based targeted metabolomics and 16S rRNA gene sequence analysis, semi-quantitatively compared the effects of 10-day UFP exposures on obese C57B6 mouse gut microbial population, changes in diversity and community function compared to a phosphate buffer solution (PBS) control group. Our results show that sex-specific differences in the gut microbial population in response to UFP exposure can be observed, as UFPs appear to have a differential impact on several bacterial families in males and females. Meanwhile, the alteration of seventy-five metabolites from the gut microbial metabolome varied significantly (ANOVA p < 0.05) across the PBS control, B0, and B20 groups. Multivariate analyses revealed that the fuel-type specific disruption to the microbial metabolome was observed in both sexes, with stronger disruptive effects found in females in comparison to male obese mice. Metabolic signatures of bacterial cellular oxidative stress, such as the decreased concentration of nucleotides and lipids and increased concentrations of carbohydrate, energy, and vitamin metabolites were detected. Furthermore, blood metabolites from the obese mice were differentially affected by the fuel types used to generate the UFPs (B0 vs. B20).

scholarly journals Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Mouse Model ◽  
High Fat Diet ◽  
Liver Diseases ◽  
Liver Weight ◽  
Control Group ◽  
High Fat ◽  
Herbal Formulation ◽  
Plants Extract

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.

scholarly journals Metatranscriptomic analysis of colonic microbiota’s functional response to different dietary fibers in growing pigs

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Jie Xu ◽  
Rongying Xu ◽  
Menglan Jia ◽  
Yong Su ◽  
Weiyun Zhu
Keyword(s):  
Gene Expression ◽  
Functional Response ◽  
Relative Abundance ◽  
Expression Profiles ◽  
Nutrient Digestibility ◽  
Growing Pigs ◽  
Control Group ◽  
Dietary Fibers ◽  
Microbial Composition ◽  
Colonic Microbiota

Abstract Background Dietary fibers are widely considered to be beneficial to health as they produce nutrients through gut microbial fermentation while facilitating weight management and boosting gut health. To date, the gene expression profiles of the carbohydrate active enzymes (CAZymes) that respond to different types of fibers (raw potato starch, RPS; inulin, INU; pectin, PEC) in the gut microbes of pigs are not well understood. Therefore, we investigated the functional response of colonic microbiota to different dietary fibers in pigs through metatranscriptomic analysis. Results The results showed that the microbial composition and CAZyme structure of the three experimental groups changed significantly compared with the control group (CON). Based on a comparative analysis with the control diet, RPS increased the abundance of Parabacteroides, Ruminococcus, Faecalibacterium and Alloprevotella but decreased Sutterella; INU increased the relative abundance of Fusobacterium and Rhodococcus but decreased Bacillus; and PEC increased the relative abundance of the Streptococcus and Bacteroidetes groups but decreased Clostridium, Clostridioides, Intestinibacter, Gemmiger, Muribaculum and Vibrio. The gene expression of CAZymes GH8, GH14, GH24, GH38, GT14, GT31, GT77 and GT91 downregulated but that of GH77, GH97, GT3, GT10 and GT27 upregulated in the RPS diet group; the gene expression of AA4, AA7, GH14, GH15, GH24, GH26, GH27, GH38, GH101, GT26, GT27 and GT38 downregulated in the INU group; and the gene expression of PL4, AA1, GT32, GH18, GH37, GH101 and GH112 downregulated but that of CE14, AA3, AA12, GH5, GH102 and GH103 upregulated in the PEC group. Compared with the RPS and INU groups, the composition of colonic microbiota in the PEC group exhibited more diverse changes with the variation of CAZymes and Streptococcus as the main contributor to CBM61, which greatly promoted the digestion of pectin. Conclusion The results of this exploratory study provided a comprehensive overview of the effects of different fibers on nutrient digestibility, gut microbiota and CAZymes in pig colon, which will furnish new insights into the impacts of the use of dietary fibers on animal and human health.

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