scholarly journals Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254321
Author(s):  
Ning Yan ◽  
Lijuan Wang ◽  
Yiwei Li ◽  
Ting Wang ◽  
Libo Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Low Grade ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gut Dysbiosis ◽  
Junction Protein ◽  
Significant Difference ◽  
Anti Inflammation

Atherosclerosis (AS) is closely associated with chronic low-grade inflammation and gut dysbiosis. Metformin (MET) presents pleiotropic benefits in the control of chronic metabolic diseases, but the impacts of MET intervention on gut microbiota and inflammation in AS remain largely unclear. In this study, ApoE-/- mice with a high-fat diet (HFD) were adopted to assess the MET treatment. After 12 weeks of MET intervention (100mg·kg-1·d-1), relevant indications were investigated. As indicated by the pathological measurements, the atherosclerotic lesion was alleviated with MET intervention. Moreover, parameters in AS including body weights (BWs), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and malondialdehyde (MDA) were elevated; whereas high-density lipoprotein (HDL) and total superoxide dismutase (T-SOD) levels were decreased, which could be reversed by MET intervention. Elevated pro-inflammatory interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and lipopolysaccaride (LPS) in AS were decreased after MET administration. However, anti-inflammatory IL-10 showed no significant difference between AS group and AS+MET group. Consistently, accumulated macrophages in the aorta of AS were conversely lowered with MET treatment. The results of 16S rRNA sequencing and analysis displayed that the overall community of gut microbiota in AS was notably changed with MET treatment mainly through decreasing Firmicutes, Proteobacteria, Romboutsia, Firmicutes/Bacteroidetes, as well as increasing Akkermansia, Bacteroidetes, Bifidobacterium. Additionally, we found that microbiota-derived short-chain fatty acids (SCFAs) including acetic acid, propionic acid, butyric acid and valeric acid in AS were decreased, which were significantly up-regulated with MET intervention. Consistent with the attenuation of MET on gut dysbiosis, decreased intestinal tight junction protein zonula occludens-1 (ZO)-1 in AS was restored after MET supplementation. Correlation analysis showed close relationships among gut bacteria, microbial metabolites SCFAs and inflammation. Collectively, MET intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation, thus can potentially serve as an inexpensive and effective intervention for the control of the atherosclerotic cardiovascular disease.

scholarly journals Gut Dysbiosis and Immune System in Atherosclerotic Cardiovascular Disease (ACVD)

2022 ◽  
Vol 10 (1) ◽  
pp. 108
Author(s):  
Ji Youn Yoo ◽  
Sarah Sniffen ◽  
Kyle Craig McGill Percy ◽  
Veera Bramhachari Pallaval ◽  
Bojjibabu Chidipi
Keyword(s):  
Cardiovascular Disease ◽  
Immune System ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Low Grade ◽  
Host Immune System ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gut Dysbiosis ◽  
Glucagon Like Peptide 1 ◽  
Inflammation Resolution

Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, such as trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated with common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota, and its metabolites, and the host immune system could reveal promising insights into ACVD development, prognostic factors, and treatments.

scholarly journals The Gut Dysbiosis and Immune System in Atherosclerotic Cardiovascular Disease (ACVD)

2021 ◽  
Author(s):  
Ji Youn Yoo ◽  
Sarah Sniffen ◽  
Kyle McGill Percy ◽  
Bojji Babu Chidipi ◽  
Veera Bramhachari Pallaval
Keyword(s):  
Cardiovascular Disease ◽  
Immune System ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Low Grade ◽  
Host Immune System ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gut Dysbiosis ◽  
Glucagon Like Peptide 1 ◽  
Inflammation Resolution

Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, namely trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated to common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota and its metabolites, and the host immune system could reveal promising insight into ACVD development, prognostic factors, and treatments.

scholarly journals The Gut Microbiota and Healthy Aging: A Mini-Review

Gerontology ◽  
2018 ◽  
Vol 64 (6) ◽  
pp. 513-520 ◽  
Author(s):  
Sangkyu Kim ◽  
S. Michal Jazwinski
Keyword(s):  
Gut Microbiota ◽  
Individual Variation ◽  
Gut Microbiome ◽  
Chronological Age ◽  
Low Grade ◽  
Beneficial Effects ◽  
Gut Dysbiosis ◽  
Age Related ◽  
Host Health ◽  
Nutrient Signaling

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.

scholarly journals Nuciferine modulates the gut microbiota and prevents obesity in high-fat diet-fed rats

2020 ◽  
Vol 52 (12) ◽  
pp. 1959-1975
Author(s):  
Yu Wang ◽  
Weifan Yao ◽  
Bo Li ◽  
Shiyun Qian ◽  
Binbin Wei ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
16S Rrna Gene Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Low Grade ◽  
Rrna Gene Sequencing

AbstractGut microbiota dysbiosis has a significant role in the pathogenesis of metabolic diseases, including obesity. Nuciferine (NUC) is a main bioactive component in the lotus leaf that has been used as food in China since ancient times. Here, we examined whether the anti-obesity effects of NUC are related to modulations in the gut microbiota. Using an obese rat model fed a HFD for 8 weeks, we show that NUC supplementation of HFD rats prevents weight gain, reduces fat accumulation, and ameliorates lipid metabolic disorders. Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that NUC changed the diversity and composition of the gut microbiota in HFD-fed rats. In particular, NUC decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio and bacteria involved in lipid metabolism, whereas it increased the relative abundance of SCFA-producing bacteria in HFD-fed rats. Predicted functional analysis of microbial communities showed that NUC modified genes involved in LPS biosynthesis and lipid metabolism. In addition, serum metabolomics analysis revealed that NUC effectively improved HFD-induced disorders of endogenous metabolism, especially lipid metabolism. Notably, NUC promoted SCFA production and enhanced intestinal integrity, leading to lower blood endotoxemia to reduce inflammation in HFD-fed rats. Together, the anti-obesity effects of NUC may be related to modulations in the composition and potential function of gut microbiota, improvement in intestinal barrier integrity and prevention of chronic low-grade inflammation. This research may provide support for the application of NUC in the prevention and treatment of obesity.

scholarly journals Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Qiang Zeng ◽  
Dongfang Li ◽  
Yuan He ◽  
Yinhu Li ◽  
Zhenyu Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Serum Lipids ◽  
Metabolic Diseases ◽  
Density Lipoprotein ◽  
16S Rrna Gene Sequencing ◽  
High Serum ◽  
Receiver Operating Curve ◽  
Rrna Gene ◽  
Metabolic Abnormalities ◽  
Clinical Indicators

Abstract The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders (Bacteroides, Parabacteroides, Blautia, Alistipes, Romboutsia and Roseburia). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia. A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia, Romboutsia, Ruminococcus2, Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides, Roseburia, Butyricicoccus, Alistipes, Parasutterella, Parabacteroides and Clostridium IV. Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

2015 ◽  
Vol 172 (4) ◽  
pp. R167-R177 ◽  
Author(s):  
Kristine H Allin ◽  
Trine Nielsen ◽  
Oluf Pedersen
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Short Chain Fatty Acids ◽  
Intestinal Content ◽  
Low Grade ◽  
Bacterial Fermentation ◽  
Underlying Mechanisms

Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gut microbiota in the pathophysiology and pathogenesis of type 2 diabetes.

scholarly journals Gut microbiota and energy balance: role in obesity

2014 ◽  
Vol 74 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Michael Blaut
Keyword(s):  
Energy Balance ◽  
Gut Microbiota ◽  
Dietary Fibre ◽  
Metabolic Diseases ◽  
De Novo ◽  
Peptide Yy ◽  
Intestinal Microbiome ◽  
Molar Ratio ◽  
Low Grade ◽  
Dietary Fibres

The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gut microbiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long- and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated.

Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity

2014 ◽  
Vol 5 (1) ◽  
pp. 33-43 ◽  
Author(s):  
M. Remely ◽  
E. Aumueller ◽  
D. Jahn ◽  
B. Hippe ◽  
H. Brath ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Gut Microbiota ◽  
Epigenetic Regulation ◽  
Control Group ◽  
Low Grade ◽  
Type 2 Diabetics ◽  
Significant Difference

Metabolic syndrome is associated with alterations in the structure of the gut microbiota leading to low-grade inflammatory responses. An increased penetration of the impaired gut membrane by bacterial components is believed to induce this inflammation, possibly involving epigenetic alteration of inflammatory molecules such as Toll-like receptors (TLRs). We evaluated changes of the gut microbiota and epigenetic DNA methylation of TLR2 and TLR4 in three groups of subjects: type 2 diabetics under glucagon-like peptide-1 agonist therapy, obese individuals without established insulin resistance, and a lean control group. Clostridium cluster IV, Clostridium cluster XIVa, lactic acid bacteria, Faecalibacterium prausnitzii and Bacteroidetes abundances were analysed by PCR and 454 high-throughput sequencing. The epigenetic methylation in the regulatory region of TLR4 and TLR2 was analysed using bisulfite conversion and pyrosequencing. We observed a significantly higher ratio of Firmicutes/ Bacteroidetes in type 2 diabetics compared to lean controls and obese. Major differences were shown in lactic acid bacteria, with the highest abundance in type 2 diabetics, followed by obese and lean participants. In comparison, F. prausnitzii was least abundant in type 2 diabetics, and most abundant in lean controls. Methylation analysis of four CpGs in the first exon of TLR4 showed significantly lower methylation in obese individuals, but no significant difference between type 2 diabetics and lean controls. Methylation of seven CpGs in the promoter region of TLR2 was significantly lower in type 2 diabetics compared to obese subjects and lean controls. The methylation levels of both TLRs were significantly correlated with body mass index. Our data suggest that changes in gut microbiota and thus cell wall components are involved in the epigenetic regulation of inflammatory reactions. An improved diet targeted to induce gut microbial balance and in the following even epigenetic changes of pro-inflammatory genes may be effective in the prevention of metabolic syndrome.

scholarly journals EEG Changes Related to Gut Dysbiosis in Diabetes—Review

2021 ◽  
Vol 11 (24) ◽  
pp. 11871
Author(s):  
Roxana Toderean ◽  
Mihai Dimian ◽  
Claudiu Cobuz
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Disorders ◽  
Neurological Disease ◽  
Metabolic Diseases ◽  
Composition Profile ◽  
Standard Methods ◽  
Gut Dysbiosis ◽  
Obesity And Diabetes ◽  
Patients With Diabetes ◽  
Eeg Changes

Humans are facing a devastating epidemic of metabolic syndrome that is linked to the worldwide dramatic increase in obesity and diabetes. Significant evidence suggests that the intestinal microbiota plays a major role in the pathogenesis of metabolic diseases. Due to the gut–brain axis link, dysbiosis in the gut microbiota have been demonstrated in both metabolic and neurological disease. Increasing evidence suggests that the gut microbiota is very important in maintaining health and changes in its composition may contribute to psychiatric and neurodegenerative disorders. It is also in research that changes in microbiota composition profile due to diabetes are modulated by the vagus nerve. Therefore, it is plausible that disruptions in the gut microbiota may be captured through electroencephalography signaling. Several studies which used standard methods of signal processing have highlighted some changes in electroencephalographic rhythms on patients with diabetes.

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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