Yellow Wine Polyphenolic Compound Protects Against Doxorubicin-Induced Cardiotoxicity by Modulating the Composition and Metabolic Function of the Gut Microbiota

2021 ◽  
Author(s):  
Hui Lin ◽  
Liping Meng ◽  
Zhenzhu Sun ◽  
Shiming Sun ◽  
Xingxiao Huang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Gut Microbiota ◽  
Gas Chromatography Mass Spectrometry ◽  
Dependent Manner ◽  
Polyphenolic Compound ◽  
Dietary Polyphenols ◽  
Microbial Dysbiosis ◽  
Myocardial Apoptosis ◽  
Rdna Sequencing

Background: Dietary polyphenols help to prevent cardiovascular diseases, and interactions between polyphenols and gut microbiota are known to exist. In this study, we speculated that gut microbiota-mediated metabolite regulation might contribute to the anticardiotoxic effects of yellow wine polyphenolic compound (YWPC) in doxorubicin (DOX)-treated rats. Methods: 16S-rDNA sequencing was performed to analyze the effects of YWPC on the gut microbiota in DOX-treated rats (n=6). Antibiotics were used to investigate the contribution of the altered microbiome to the role of YWPC (n=6). Plasma metabolomics were also analyzed by untargeted gas chromatography-mass spectrometry systems. Results: YWPC ameliorated DOX-mediated cardiotoxicity, as evidenced by increased cardiac and mitochondrial function and reduced levels of inflammation and myocardial apoptosis ( P <0.05 for all). The low abundance of Escherichia – Shigella , Dubosiella , and Allobaculum , along with enrichment of Muribaculaceae_unclassified , Ralstonia , and Rikenellaceae_RC9_gut_group in the gut, suggested that YWPC ameliorated DOX-induced microbial dysbiosis. YWPC also influenced the levels of metabolites altered by DOX, resulting in lower arachidonic acid and linoleic acid metabolism and higher tryptophan metabolite levels ( P <0.05 for all). Correlational studies indicated that YWPC alleviated DOX-induced inflammation and mitochondrial dysfunction by modulating the gut microbial community and its associated metabolites. Antibiotic treatment exacerbated cardiotoxicity in DOX-treated rats, and its effect on the gut microbiota partly abolished the anticardiotoxic effects of YWPC, suggesting that the microbiota is required for the cardioprotective role of YWPC. Conclusions: YWPC protected against DOX-induced cardiotoxicity in a gut microbiota–dependent manner. This supports the use of dietary polyphenols as a therapeutic approach for the treatment of cardiovascular diseases via microbiota regulation.

scholarly journals Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhangjian Chen ◽  
Di Zhou ◽  
Shuo Han ◽  
Shupei Zhou ◽  
Guang Jia
Keyword(s):  
Titanium Dioxide ◽  
Gut Microbiota ◽  
Titanium Dioxide Nanoparticles ◽  
Oral Exposure ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Indirect Pathway ◽  
Rdna Sequencing ◽  
Underlying Mechanisms

Abstract Background Due to its excellent physicochemical properties and wide applications in consumer goods, titanium dioxide nanoparticles (TiO2 NPs) have been increasingly exposed to the environment and the public. However, the health effects of oral exposure of TiO2 NPs are still controversial. This study aimed to illustrate the hepatotoxicity induced by TiO2 NPs and the underlying mechanisms. Rats were administered with TiO2 NPs (29 nm) orally at exposure doses of 0, 2, 10, 50 mg/kg daily for 90 days. Changes in the gut microbiota and hepatic metabolomics were analyzed to explore the role of the gut-liver axis in the hepatotoxicity induced by TiO2 NPs. Results TiO2 NPs caused slight hepatotoxicity, including clear mitochondrial swelling, after subchronic oral exposure at 50 mg/kg. Liver metabolomics analysis showed that 29 metabolites and two metabolic pathways changed significantly in exposed rats. Glutamate, glutamine, and glutathione were the key metabolites leading the generation of energy-related metabolic disorders and imbalance of oxidation/antioxidation. 16S rDNA sequencing analysis showed that the diversity of gut microbiota in rats increased in a dose-dependent manner. The abundance of Lactobacillus_reuteri increased and the abundance of Romboutsia decreased significantly in feces of TiO2 NPs-exposed rats, leading to changes of metabolic function of gut microbiota. Lipopolysaccharides (LPS) produced by gut microbiota increased significantly, which may be a key factor in the subsequent liver effects. Conclusions TiO2 NPs could induce slight hepatotoxicity at dose of 50 mg/kg after long-term oral exposure. The indirect pathway of the gut-liver axis, linking liver metabolism and gut microbiota, played an important role in the underlying mechanisms.

scholarly journals The Emerging Role of Gut Microbiota in Cardiovascular Diseases

2021 ◽  
Author(s):  
Dilip Kumar ◽  
Sanjeev S. Mukherjee ◽  
Rabin Chakraborty ◽  
Rana Rathod Roy ◽  
Arindam Pandey ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Gut Microbiota

scholarly journals Sirt5 deficiency causes post-translational protein malonylation and dysregulated cellular metabolism in chondrocytes under obesity conditions

2020 ◽  
Author(s):  
Shouan Zhu ◽  
Albert Batushansky ◽  
Anita Jopkiewicz ◽  
Dawid Makosa ◽  
Kenneth M. Humphries ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Tca Cycle ◽  
Gas Chromatography Mass Spectrometry ◽  
Dependent Manner ◽  
Joint Injury ◽  
Primary Chondrocytes ◽  
Wide Range ◽  
Chondrocyte Metabolism ◽  
High Concentrations

ABSTRACTObjectiveObesity accelerates the development of osteoarthritis (OA) during aging and is associated with altered chondrocyte cellular metabolism. The objective of this study was to investigate the role of sirtuin 5 (SIRT5) in regulating chondrocyte protein lysine malonylation (MaK) and cellular metabolism under obesity-related conditions.MethodsMaK and SIRT5 were immunostained in knee articular cartilage of obese db/db mice and different aged C57BL6 mice with or without destabilization of the medial meniscus (DMM) surgery to induce OA. Primary chondrocytes were isolated from 7-day-old WT and Sirt5−/− mice and treated with varying concentrations of glucose and insulin to mimic obesity. Sirt5-dependent effects on MaK and metabolism were evaluated by Western blot, Seahorse Respirometry, and gas/chromatography-mass/spectrometry (GC-MS) metabolic profiling.ResultsMaK was significantly increased in cartilage of db/db mice and in chondrocytes treated with high concentrations of glucose and insulin (GluhiInshi). Sirt5 protein was increased in an age-dependent manner following joint injury, and Sirt5 deficient primary chondrocytes had increased MaK, decreased glycolysis rate, and reduced basal mitochondrial respiration. GC-MS identified 41 metabolites. Sirt5 deficiency altered 13 distinct metabolites under basal conditions and 18 metabolites under GluhiInshi treatment. Pathway analysis identified a wide range of Sirt5-dependent altered metabolic pathways that include amino acid metabolism, TCA cycle, and glycolysis.ConclusionThis study provides the first evidence that Sirt5 broadly regulates chondrocyte metabolism. We observed changes in Sirt5 and MaK levels in cartilage with obesity and joint injury, suggesting that the Sirt5-MaK pathway may contribute to altered chondrocyte metabolism that occurs during OA development.

scholarly journals Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

2021 ◽  
Author(s):  
Yiyangzi Ma ◽  
Ruru Guo ◽  
Yiduo Sun ◽  
Xin Li ◽  
Lun He ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lupus Erythematosus ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Healthy Controls ◽  
Germ Free ◽  
Autoimmune Antibodies ◽  
Expression Of Genes ◽  
Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

scholarly journals Impact of Nutrition on Pulmonary Arterial Hypertension

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 169
Author(s):  
María Callejo ◽  
Joan Albert Barberá ◽  
Juan Duarte ◽  
Francisco Perez-Vizcaino
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Animal Models ◽  
Gut Microbiota ◽  
Arterial Hypertension ◽  
Case Reports ◽  
Host Immune System ◽  
Dietary Polyphenols ◽  
Pulmonary Arterial ◽  
Near Future

Pulmonary arterial hypertension (PAH) is characterized by sustained vasoconstriction, vascular remodeling, inflammation, and in situ thrombosis. Although there have been important advances in the knowledge of the pathophysiology of PAH, it remains a debilitating, limiting, and rapidly progressive disease. Vitamin D and iron deficiency are worldwide health problems of pandemic proportions. Notably, these nutritional alterations are largely more prevalent in PAH patients than in the general population and there are several pieces of evidence suggesting that they may trigger or aggravate disease progression. There are also several case reports associating scurvy, due to severe vitamin C deficiency, with PAH. Flavonoids such as quercetin, isoflavonoids such as genistein, and other dietary polyphenols including resveratrol slow the progression of the disease in animal models of PAH. Finally, the role of the gut microbiota and its interplay with the diet, host immune system, and energy metabolism is emerging in multiple cardiovascular diseases. The alteration of the gut microbiota has also been reported in animal models of PAH. It is thus possible that in the near future interventions targeting the nutritional status and the gut dysbiosis will improve the outcome of these patients.

scholarly journals Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Chao Kang ◽  
Bin Wang ◽  
Kanakaraju Kaliannan ◽  
Xiaolan Wang ◽  
Hedong Lang ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Rrna Gene ◽  
Low Grade ◽  
High Fat ◽  
Microbial Dysbiosis ◽  
Low Grade Inflammation ◽  
Metabolic Endotoxemia

ABSTRACT Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation. IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP. Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP.

Role of Dietary Polyphenols and Inflammatory Processes on Disease Progression Mediated by the Gut Microbiota

2013 ◽  
Vol 16 (5) ◽  
pp. 435-437 ◽  
Author(s):  
J. Alfredo Martínez ◽  
Usune Etxeberría ◽  
Alicia Galar ◽  
Fermín I. Milagro
Keyword(s):  
Gut Microbiota ◽  
Disease Progression ◽  
Dietary Polyphenols ◽  
Inflammatory Processes

scholarly journals Implication of Gut Microbiota in Cardiovascular Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Wenyi Zhou ◽  
Yiyu Cheng ◽  
Ping Zhu ◽  
M. I. Nasser ◽  
Xueyan Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Programmed Cell Death ◽  
Gut Microbiota ◽  
Intestinal Flora ◽  
Short Chain Fatty Acids ◽  
Secondary Bile Acid ◽  
Cardiac Disorders ◽  
The Relationship

Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.

scholarly journals The Short-Term Effect of a High-Glycemic Diet on Mouse Obesity and Intestinal Microbiota Composition

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1602-1602
Author(s):  
Ying Zhu ◽  
Kelsey Smith ◽  
Sheldon Rowan ◽  
Andrew Greenberg
Keyword(s):  
Gut Microbiota ◽  
Glycemic Index ◽  
Relative Role ◽  
Microbiota Composition ◽  
Metabolic Complications ◽  
Rdna Sequencing ◽  
High Glycemic Index ◽  
Mouse Obesity ◽  
Similar Body

Abstract Objectives High glycemic index diet has been demonstrated to induce obesity and insulin resistance. The role of gut microbiota, as a key mediator of several metabolic syndromes, has not been elucidated. The objective of this project is to understand the effect of gut microbiota in a high-glycemic diet-induced obesity and associated metabolic complications. Methods Male C57Bl6/J mice aged 8–9 weeks were fed with a high-glycemic diet (HG, amylopectin-based) or low-glycemic diet (LG, amylose-based) ad libitum for 8 weeks. Body composition was determined by MRIs. Intraperitoneal glucose tolerance tests were performed after 6 weeks on diet. Mice were euthanized after 8 weeks on diet. Results After two weeks on diet, the HG group (n = 12) mice had a significantly higher body fat mass by MRI analysis, as compared to the LG group (n = 12) despite having similar body weight and equal food consumption. After 6 weeks, mice in the HG group had a significantly higher fasting glucose level compared to the LG group. There was no difference in fasting triglyceride level. Gonadal, subcutaneous and brown fat adipose tissue weight were significantly higher in the HG group after 8 weeks on diet. 16S rDNA sequencing on feces showed that the HG mice have a significantly higher Shannon diversity and different overall microbiome structure compared to the LG mice. The microbial community in the LG group was predominated by Bacteroidetes, particularly by Bacteroides thetaiotaomicron (Relative abundance 48.65 ± 12.88% versus HG 14.69 ± 0.07%), while the HG group was predominated by Firmicutes. Ongoing analysis will investigate the relative role of key microbial taxa on obesity and glucose homeostasis. Conclusions Consuming two weeks of a high-glycemic index diet induced adiposity and hyperglycemia along with a shift of the overall gut microbiota composition compared to a low-glycemic index diet. Funding Sources NIH, USDA, Robert C and Veronica Atkins Foundation

scholarly journals Role of Dietary Lipids in Modulating Inflammation through the Gut Microbiota

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 117 ◽  
Author(s):  
Paul J. Wisniewski ◽  
Robert A. Dowden ◽  
Sara C. Campbell
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Dietary Lipids ◽  
Taxonomic Resolution ◽  
Low Grade ◽  
Energy Regulation ◽  
Microbial Dysbiosis

Inflammation and its resolution is a tenuous balance that is under constant contest. Though several regulatory mechanisms are employed to maintain homeostasis, disruptions in the regulation of inflammation can lead to detrimental effects for the host. Of note, the gut and microbial dysbiosis are implicated in the pathology of systemic chronic low-grade inflammation which has been linked to several metabolic diseases. What remains to be described is the extent to which dietary fat and concomitant changes in the gut microbiota contribute to, or arise from, the onset of metabolic disorders. The present review will highlight the role of microorganisms in host energy regulation and several mechanisms that contribute to inflammatory pathways. This review will also discuss the immunomodulatory effects of the endocannabinoid system and its link with the gut microbiota. Finally, a brief discussion arguing for improved taxonomic resolution (at the species and strain level) is needed to deepen our current knowledge of the microbiota and host inflammatory state.

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