Resveratrol and the Interaction between Gut Microbiota and Arterial Remodelling

Arterial remodelling refers to the alteration in the structure of blood vessel that contributes to the progression of hypertension and other cardiovascular complications. Arterial remodelling is orchestrated by the crosstalk between the endothelium and vascular smooth muscle cells (VSMC). Vascular inflammation participates in arterial remodelling. Resveratrol is a natural polyphenol that possesses anti-oxidant and anti-inflammatory properties and has beneficial effects in both the endothelium and VSMC. Resveratrol has been studied for the protective effects in arterial remodelling and gut microbiota, respectively. Gut microbiota plays a critical role in the immune system and inflammatory processes. Gut microbiota may also regulate vascular remodelling in cardiovascular complications via affecting endothelium function and VSMC proliferation. Currently, there is new evidence showing that gut microbiota regulate the proliferation of VSMC and the formation of neointimal hyperplasia in response to injury. The change in population of the gut microbiota, as well as their metabolites (e.g., short-chain fatty acids) could critically contribute to VSMC proliferation, cell cycle progression, and migration. Recent studies have provided strong evidence that correlate the effects of resveratrol in arterial remodelling and gut microbiota. This review aims to summarize recent findings on the resveratrol effects on cardiovascular complications focusing on arterial remodelling and discuss the possible interactions of resveratrol and the gut microbiota that modulate arterial remodelling.

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The Protective Effects of 2’-Fucosyllactose Against E. Coli O157 Infection Are Mediated by the Regulation of Gut Microbiota and the Inhibition of Pathogen Adhesion

Nutrients ◽

10.3390/nu12051284 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1284 ◽

Cited By ~ 2

Author(s):

Yuanyifei Wang ◽

Yan Zou ◽

Jin Wang ◽

Hui Ma ◽

Bowei Zhang ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Inflammation ◽

Foodborne Pathogen ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Intestinal Barrier Function ◽

Protective Effects ◽

E Coli ◽

Beneficial Effects

As the richest component in human milk oligosaccharides (HMOs), 2’-fucosyllactose (2’-FL) can reduce the colonization of harmful microbiota in vivo, thus lowering the risk of infection; however, the mechanism for this is still unclear. In this study, a model of Escherichia coli O157 infection in healthy adult mice was established to explore the effect of 2’-FL intervention on E. coli O157 colonization and its protective effects on mice. The results showed that 2’-FL intake reduced E. coli O157 colonization in mice intestine by more than 90% (p < 0.001), and it also reduced intestinal inflammation, increased the content of fecal short-chain fatty acids, and enhanced intestinal barrier function. These beneficial effects were attributed to the increased expression of mucins such as MUC2 (increased by more than 20%, p < 0.001), and inhibition of E. coli O157 cell adhesion (about 30% reduction, p < 0.001), and were associated with the modulation of gut microbiota composition. 2’-FL significantly increased the abundance of Akkermansia, a potential probiotic, which may represent the fundamental means by which 2’-FL enhances the expression of mucin and reduces the colonization of harmful bacteria. The current study may support the use of 2’-FL in the prevention of foodborne pathogen infections in human.

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Gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice

Food & Function ◽

10.1039/d1fo00709b ◽

2021 ◽

Author(s):

Chenyang Lu ◽

Ju Chen ◽

Congmin Yi ◽

Jiaojiao Han ◽

Qiuyue Shi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Gut Microbiota ◽

Protective Effects ◽

Collagen Induced Arthritis ◽

Tuna Oil ◽

Beneficial Effects ◽

Chronic Autoimmune Disease

Rheumatoid arthritis is emerging as a chronic autoimmune disease worldwide. In this study, the components of tuna oil (TO) were firstly measured, and the beneficial effects of TO on collagen-induced...

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Abstract 47: FXR1 Regulates Inflammatory MRNA Stability and VSMC Proliferation by Modulation of HuR Activity

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.47 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Allison Herman ◽

Ross England ◽

Dale Haines ◽

Sheri Kelemen ◽

Mitali Ray ◽

...

Keyword(s):

Mrna Stability ◽

Fragile X ◽

Vascular Inflammation ◽

Critical Role ◽

Vascular Diseases ◽

Muscle Cells ◽

Vsmc Proliferation ◽

Inflammatory Conditions ◽

Mass Spec ◽

Inflammatory Proteins

Vascular smooth muscle cells (VSMC) play a critical role in the etiology and progression of many vascular diseases including atherosclerosis and restenosis. Our laboratory has found that one anti-inflammatory interleukin, IL-19, is atheroprotective and can decrease vascular inflammation by reduction in mRNA stability of inflammatory transcripts by reduction of activity of HuR, an mRNA stability protein. HuR translocates from the nucleus to the cytoplasm where it recognizes AU-rich elements present almost exclusively in the 3’UTR of pro-inflammatory genes. Proteins and pathways which limit HuR translocation are understudied, but may reduce inflammatory mRNA stability. Using MASS SPEC to identify HuR-interacting proteins under different inflammatory conditions, we identified one protein, Fragile X-related protein (FXR1), which interacts with HuR in inflammatory, but not basal conditions, a novel interaction. FXR1 mRNA expression is enhanced in muscle cells, but nothing has been reported on expression of FXR1 in VSMC or function for FXR1 in vascular disease. The FXR1 promoter contains multiple cholesterol-response elements, and in this study we demonstrate that FXR1 expression is increased in injured arteries and TNFα and oxLDL stimulated human VSMC, but also by IL-19. RNA EMSA demonstrates that FXR1 directly interacts with ARE in 3’UTR. SiRNA knock down of FXR1 in VSMC increases stability of inflammatory mRNA and protein abundance as well as VSMC proliferation, while overexpression of FXR1 reduces both their abundance and stability in addition to reducing proliferation. Since FXR1 appears to be a novel repressor of inflammatory proteins, and is also induced by IL-19, our overall hypothesis is that FXR1 expression and HuR interaction is an inflammation responsive, counter-regulatory mechanism to reduce abundance of pro-inflammatory proteins and therefore reduce inflammation.

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Abstract 15691: The Novel High Mobility Group Protein Hmgxb4 Promotes Neointimal Formation in Response to Arterial Injury

Circulation ◽

10.1161/circ.142.suppl_3.15691 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

xiangqin he ◽

Kunzhe Dong ◽

Jian Shen ◽

Islam Osman ◽

Guoqing Hu ◽

...

Keyword(s):

Smooth Muscle ◽

Neointimal Hyperplasia ◽

Critical Role ◽

High Mobility ◽

Arterial Injury ◽

The Novel ◽

Neointimal Formation ◽

Vsmc Proliferation ◽

And Migration

Introduction: Restenosis after percutaneous intervention is predominantly attributed to proliferation and migration of vascular smooth muscle cells (VSMCs). However, the key regulators responsible for VSMC proliferation and migration remain to be identified. Hypothesis: We previously reported that the novel high mobility group (HMG) nuclear protein HMGXB4 (HMG-Box containing 4) plays a critical role in the de-differentiation of vascular smooth muscle cells in vitro and in acute inflammatory response to septic shock. We hypothesize that HMGXB4 is critical for neointimal hyperplasia in response to inflammatory stimuli. Methods and Results: We found that the expression of HMGXB4 is dramatically induced in ligation or wire injury-induced neointimal hyperplasia and correlated with the activation of inflammatory signaling in mice. Using an inducible smooth muscle-specific Hmgxb4 KO (knockout) mice model, we found specific KO of Hmgxb4 in VSMCs ameliorates ligation- or wire- injury induced neointimal formation. Among an array of growth factors and inflammation cytokines, we found that TNFα and INFγ effectively induces the expression of HMGXB4 in VSMCs and correlates with the VSMC proliferation in vitro. Furthermore, we found deletion of HMGXB4 attenuates while over-expression of HMGXB4 promotes inflammation cytokines-induced VSMC proliferation in vitro. These results suggest injury-induced inflammatory signal triggers HMGXB4 induction, which, in turn, promotes the VSMC proliferation and neointimal formation. Conclusions: Our study not only demonstrates a critical role of HMGXB4 in promoting neointimal hyperplasia in response the arterial injury, but also suggests HMGXB4 is a potential novel target for the management of restenosis in human.

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Gut Microbiome: Profound Implications for Diet and Disease

Nutrients ◽

10.3390/nu11071613 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1613 ◽

Cited By ~ 83

Author(s):

Ronald Hills ◽

Benjamin Pontefract ◽

Hillary Mishcon ◽

Cody Black ◽

Steven Sutton ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Bacterial Species ◽

Intestinal Bacteria ◽

Short Chain Fatty Acids ◽

E Coli ◽

Beneficial Effects ◽

Microbial Profile ◽

Irritable Bowel ◽

Prebiotic Fiber

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease.

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Altered Gut Microbiota in Korean Children with Autism Spectrum Disorders

Nutrients ◽

10.3390/nu13103300 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3300

Author(s):

Sungji Ha ◽

Donghun Oh ◽

Sunghee Lee ◽

Jaewan Park ◽

Jaeun Ahn ◽

...

Keyword(s):

Gut Microbiota ◽

Neurodevelopmental Disorder ◽

Critical Role ◽

Short Chain Fatty Acids ◽

Bioinformatic Analysis ◽

Autism Spectrum ◽

Korean Children ◽

Children With Asd ◽

Genetic Information Processing ◽

Behavioral Impairments

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and behavioral impairments. Recent studies have suggested that gut microbiota play a critical role in ASD pathogenesis. Herein, we investigated the fecal microflora of Korean ASD children to determine gut microbiota profiles associated with ASD. Specifically, fecal samples were obtained from 54 children with ASD and 38 age-matched children exhibiting typical development. Systematic bioinformatic analysis revealed that the composition of gut microbiota differed between ASD and typically developing children (TDC). Moreover, the total amounts of short-chain fatty acids, metabolites produced by bacteria, were increased in ASD children. At the phylum level, we found a significant decrease in the relative Bacteroidetes abundance of the ASD group, whereas Actinobacteria abundance was significantly increased. Furthermore, we found significantly lower Bacteroides levels and higher Bifidobacterium levels in the ASD group than in the TDC group at the genus level. Functional analysis of the microbiota in ASD children predicted that several pathways, including genetic information processing and amino acid metabolism, can be associated with ASD pathogenesis. Although more research is needed to determine whether the differences between ASD and TDC are actually related to ASD pathogenesis, these results provide further evidence of altered gut microbiota in children with ASD, possibly providing new perspectives on the diagnosis and therapeutic approaches for ASD patients.

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Cereus sinensis Polysaccharide Alleviates Antibiotic-Associated Diarrhea Based on Modulating the Gut Microbiota in C57BL/6 Mice

Frontiers in Nutrition ◽

10.3389/fnut.2021.751992 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mingxiao Cui ◽

Yu Wang ◽

Jeevithan Elango ◽

Junwen Wu ◽

Kehai Liu ◽

...

Keyword(s):

Gut Microbiota ◽

High Throughput Sequencing ◽

Interleukin 2 ◽

Intestinal Flora ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Gas Chromatography Mass Spectrometry ◽

Enzyme Linked Immunosorbent Assay ◽

Beneficial Effects ◽

Antibiotic Associated Diarrhea

The present study investigated whether the purified polysaccharide from Cereus sinensis (CSP-1) had beneficial effects on mice with antibiotic-associated diarrhea (AAD). The effects of CSP-1 on gut microbiota were evaluated by 16S rRNA high-throughput sequencing. Results showed that CSP-1 increased the diversity and richness of gut microbiota. CSP-1 enriched Phasecolarctobacterium, Bifidobacterium and reduced the abundance of Parabacteroides, Sutterella, Coprobacillus to near normal levels, modifying the gut microbial community. Microbial metabolites were further analyzed by gas chromatography-mass spectrometry (GC-MS). Results indicated CSP-1 promoted the production of various short-chain fatty acids (SCFAs) and significantly improved intestinal microflora dysfunction in AAD mice. In addition, enzyme linked immunosorbent assay and hematoxylin-eosin staining were used to assess the effects of CSP-1 on cytokine levels and intestinal tissue in AAD mice. Results demonstrated that CSP-1 inhibited the secretion of interleukin-2 (IL-2), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and improved the intestinal barrier. Correspondingly, the daily records also showed that CSP-1 promoted recovery of diarrhea status score, water intake and body weight in mice with AAD. In short, CSP-1 helped alleviate AAD by regulating the inflammatory cytokines, altering the composition and richness of intestinal flora, promoting the production of SCFAs, improving the intestinal barrier as well as reversing the dysregulated microbiota function.

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Longitudinal Multi-Omics Study of a Mother-Infant Dyad from Breastfeeding to Weaning: An Individualized Approach to Understand the Interactions Among Diet, Fecal Metabolome and Microbiota Composition

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.688440 ◽

2021 ◽

Vol 8 ◽

Author(s):

Giorgia Conta ◽

Federica Del Chierico ◽

Sofia Reddel ◽

Federico Marini ◽

Fabio Sciubba ◽

...

Keyword(s):

Breast Milk ◽

Gut Microbiota ◽

Single Mother ◽

Critical Role ◽

Short Chain Fatty Acids ◽

Lactation Period ◽

Common Component ◽

Sequence Of Events ◽

16S Rna ◽

Stool Samples

The development of the human gut microbiota is characterized by a dynamic sequence of events from birth to adulthood, which make the gut microbiota unique for everyone. Its composition and metabolism may play a critical role in the intestinal homeostasis and health. We propose a study on a single mother-infant dyad to follow the dynamics of an infant fecal microbiota and metabolome changes in relation to breast milk composition during the lactation period and evaluate the changes induced by introduction of complementary food during the weaning period. Nuclear Magnetic Resonance (NMR)-based metabolomics was performed on breast milk and, together with 16S RNA targeted-metagenomics analysis, also on infant stool samples of a mother-infant dyad collected over a period running from the exclusive breastfeeding diet to weaning. Breast milk samples and neonatal stool samples were collected from the 4th to the 10th month of life. Both specimens were collected from day 103 to day 175, while from day 219–268 only stool samples were examined. An exploratory and a predictive analysis were carried out by means of Common component and specific weight analysis and multi-block partial least squares discriminant analysis, respectively. Stools collected during breastfeeding and during a mixed fruit/breastfeeding diet were characterized by high levels of fucosyl-oligosaccharides and glycolysis intermediates, including succinate and formate. The transition to a semi-solid food diet was characterized by several changes in fecal parameters: increase in short-chain fatty acids (SCFAs) levels, including acetate, propionate and butyrate, dissapearance of HMOs and the shift in the community composition, mainly occurring within the Firmicutes phylum. The variations in the fecal metabolome reflected the infant’s diet transition, while the composition of the microbiota followed a more complex and still unstable behavior.

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Modulation of the Gut Microbiota by Olive Oil Phenolic Compounds: Implications for Lipid Metabolism, Immune System, and Obesity

Nutrients ◽

10.3390/nu12082200 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2200

Author(s):

Marta Farràs ◽

Laura Martinez-Gili ◽

Kevin Portune ◽

Sara Arranz ◽

Gary Frost ◽

...

Keyword(s):

Clinical Trials ◽

Immune System ◽

Lipid Metabolism ◽

Phenolic Compounds ◽

Gut Microbiota ◽

Olive Oil ◽

Cholesterol Metabolism ◽

Virgin Olive Oil ◽

Short Chain Fatty Acids ◽

Beneficial Effects

There is extensive information of the beneficial effects of virgin olive oil (VOO), especially on cardiovascular diseases. Some VOO healthy properties have been attributed to their phenolic-compounds (PCs). The aim of this review is to present updated data on the effects of olive oil (OO) PCs on the gut microbiota, lipid metabolism, immune system, and obesity, as well as on the crosstalk among them. We summarize experiments and clinical trials which assessed the specific effects of the olive oil phenolic-compounds (OOPCs) without the synergy with OO-fats. Several studies have demonstrated that OOPC consumption increases Bacteroidetes and/or reduces the Firmicutes/Bacteroidetes ratio, which have both been related to atheroprotection. OOPCs also increase certain beneficial bacteria and gut-bacteria diversity which can be therapeutic for lipid-immune disorders and obesity. Furthermore, some of the mechanisms implicated in the crosstalk between OOPCs and these disorders include antimicrobial-activity, cholesterol microbial metabolism, and metabolites produced by bacteria. Specifically, OOPCs modulate short-chain fatty-acids produced by gut-microbiota, which can affect cholesterol metabolism and the immune system, and may play a role in weight gain through promoting satiety. Since data in humans are scarce, there is a necessity for more clinical trials designed to assess the specific role of the OOPCs in this crosstalk.

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Grape Seed Procyanidin B2 Protects Porcine Ovarian Granulosa Cells against Oxidative Stress-Induced Apoptosis by Upregulating let-7a Expression

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1076512 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

Jia-Qing Zhang ◽

Xian-Wei Wang ◽

Jun-Feng Chen ◽

Qiao-Ling Ren ◽

Jing Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Critical Role ◽

Grape Seed ◽

Luciferase Reporter ◽

Tunel Staining ◽

Protective Effects ◽

Beneficial Effects ◽

Protein Levels ◽

Underlying Mechanisms ◽

Induced Apoptosis

Oxidative stress is a causal factor and key promoter of all kinds of reproductive disorders related to granulosa cell (GC) apoptosis that acts by dysregulating the expression of related genes. Various studies have suggested that grape seed procyanidin B2 (GSPB2) may protect GCs from oxidative injury, though the underlying mechanisms are not fully understood. Therefore, whether the beneficial effects of GSPB2 are associated with microRNAs, which have been suggested to play a critical role in GC apoptosis by regulating the expression of protein-coding genes, was investigated in this study. The results showed that GSPB2 treatment protected GCs from a H2O2-induced apoptosis, as detected by an MTT assay and TUNEL staining, and increased let-7a expression in GCs. Furthermore, let-7a overexpression markedly increased cell viability and inhibited H2O2-induced GC apoptosis. Furthermore, the overexpression of let-7a reduced the upregulation of Fas expression in H2O2-treated GCs at the mRNA and protein levels. Dual-luciferase reporter assay results indicated that let-7a directly targets the Fas 3′-UTR. Furthermore, the overexpression of let-7a enhanced the protective effects of GSPB2 against GC apoptosis induced by H2O2. These results indicate that GSPB2 inhibits H2O2-induced apoptosis of GCs, possibly through the upregulation of let-7a.

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