scholarly journals Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver

2021 ◽  
Vol 10 (3) ◽  
pp. 541
Author(s):  
Haripriya Gupta ◽  
Ki Tae Suk ◽  
Dong Joon Kim
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Potential ◽  
Strong Association ◽  
Short Chain Fatty Acids ◽  
Experimental Models ◽  
Future Research ◽  
Low Grade ◽  
Brain Disorders ◽  
Alcohol Abstinence ◽  
Alcoholic Liver Diseases

Over the last decade, increased research into the cognizance of the gut–liver–brain axis in medicine has yielded powerful evidence suggesting a strong association between alcoholic liver diseases (ALD) and the brain, including hepatic encephalopathy or other similar brain disorders. In the gut–brain axis, chronic, alcohol-drinking-induced, low-grade systemic inflammation is suggested to be the main pathophysiology of cognitive dysfunctions in patients with ALD. However, the role of gut microbiota and its metabolites have remained unclear. Eubiosis of the gut microbiome is crucial as dysbiosis between autochthonous bacteria and pathobionts leads to intestinal insult, liver injury, and neuroinflammation. Restoring dysbiosis using modulating factors such as alcohol abstinence, promoting commensal bacterial abundance, maintaining short-chain fatty acids in the gut, or vagus nerve stimulation could be beneficial in alleviating disease progression. In this review, we summarize the pathogenic mechanisms linked with the gut–liver–brain axis in the development and progression of brain disorders associated with ALD in both experimental models and humans. Further, we discuss the therapeutic potential and future research directions as they relate to the gut–liver–brain axis.

scholarly journals Guidelines for Transparency on Gut Microbiome Studies in Essential and Experimental Hypertension

Hypertension ◽  
2019 ◽  
Vol 74 (6) ◽  
pp. 1279-1293 ◽  
Author(s):  
Francine Z. Marques ◽  
Hamdi A. Jama ◽  
Kirill Tsyganov ◽  
Paul A. Gill ◽  
Dakota Rhys-Jones ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Environmental Factors ◽  
Gut Microbiota ◽  
Environmental History ◽  
Gut Microbiome ◽  
Blood Pressure Measurement ◽  
Short Chain Fatty Acids ◽  
Experimental Models ◽  
Human Studies ◽  
Experimental Hypertension

Hypertension is a complex and modifiable condition in which environmental factors contribute to both onset and progression. Recent evidence has accumulated for roles of diet and the gut microbiome as environmental factors in blood pressure regulation. However, this is complex because gut microbiomes are a unique feature of each individual reflecting that individual’s developmental and environmental history creating caveats for both experimental models and human studies. Here, we describe guidelines for conducting gut microbiome studies in experimental and clinical hypertension. We provide a complete guide for authors on proper design, analyses, and reporting of gut microbiota/microbiome and metabolite studies and checklists that can be used by reviewers and editors to support robust reporting and interpretation. We discuss factors that modulate the gut microbiota in animal (eg, cohort, controls, diet, developmental age, housing, sex, and models used) and human studies (eg, blood pressure measurement and medication, body mass index, demographic characteristics including age, cultural identification, living structure, sex and socioeconomic environment, and exclusion criteria). We also provide best practice advice on sampling, storage of fecal/cecal samples, DNA extraction, sequencing methods (including metagenomics and 16S rRNA), and computational analyses. Finally, we discuss the measurement of short-chain fatty acids, metabolites produced by the gut microbiota, and interpretation of data. These guidelines should support better transparency, reproducibility, and translation of findings in the field of gut microbiota/microbiome in hypertension and cardiovascular disease.

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 Comprehensive Bibliometric Analysis of the Kynurenine Pathway in Mood Disorders: Focus on Gut Microbiota Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiuqing Zhu ◽  
Jinqing Hu ◽  
Shuhua Deng ◽  
Yaqian Tan ◽  
Chang Qiu ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Citation Analysis ◽  
Mood Disorders ◽  
Bibliometric Analysis ◽  
The United States ◽  
Kynurenine Pathway ◽  
Current Status ◽  
Future Research ◽  
Low Grade

Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system.Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field.Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16).Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, “quinolinic acid.” All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were “kynurenine pathway,” “psychoneuroimmunology,” “indoleamine 2,3-dioxygenase,” and “proinflammatory cytokines,” and the most recent focus was “gut-brain axis,” thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field’s research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics “Alzheimer’s disease,” “prefrontal cortex,” and “acid,” were research frontiers.Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field’s hotspots and frontiers, thus facilitating future research.

scholarly journals Supplementation with Sodium Butyrate Modulates the Composition of the Gut Microbiota and Ameliorates High-Fat Diet-Induced Obesity in Mice

2019 ◽  
Vol 149 (5) ◽  
pp. 747-754 ◽  
Author(s):  
Wanjun Fang ◽  
Hongliang Xue ◽  
Xu Chen ◽  
Ke Chen ◽  
Wenhua Ling
Keyword(s):  
Gut Microbiota ◽  
Chronic Inflammation ◽  
Sodium Butyrate ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Principal Component ◽  
Short Chain Fatty Acids ◽  
Low Grade ◽  
Microbiota Composition ◽  
High Fat

ABSTRACT Background Short-chain fatty acids (SCFAs) have been reported to ameliorate obesity. However, the underlying mechanisms require further investigation. Objective The aim of this study was to determine the role of butyrate, an SCFA, in the regulation of obesity, low-grade chronic inflammation, and alterations of microbiota composition in mice. Methods Male C57BL/6J mice, 4–5 wk of age, were divided into 3 groups (n = 8 mice/group): low-fat diet (LFD; 10% energy from fat), high-fat diet (HFD; 45% energy from fat), or high-fat diet plus sodium butyrate (HSB). HSB mice received sodium butyrate at a concentration of 0.1 M in drinking water for 12 wk. Measures of inflammation, obesity, and intestinal integrity were assessed. Serum lipopolysaccharide (LPS) concentrations were measured in the 3 groups. Fecal samples were collected for gut microbiota analysis. Results In HFD mice, body weight gain and hepatic triglyceride (TG), serum interleukin-6 (IL-6), and serum tumor necrosis factor (TNF)-α levels were 1–4 times higher than those in LFD mice (P < 0.05); they were 34–42% lower in HSB mice compared with HFD mice (P < 0.05). The HFD group had 28%–48% lower mRNA expression of both Tjp1 and Ocln in the ileum and colon compared with levels in LFD or HSB mice (P < 0.05), whereas there was no difference in expression levels between LFD and HSB mice. Furthermore, in HSB mice, serum LPS concentration was 53% lower compared with that in HFD mice but still 23% higher than that in LFD mice (P < 0.05). Results from principal component analysis showed that HSB and LFD mice had a similar gut microbiota structure, which was significantly different from that in HFD mice (P < 0.05). Conclusions Sodium butyrate administration beneficially changed HFD-induced gut microbiota composition and improved intestinal barrier, leading to lower serum LPS concentrations. These changes may correspond with improvements in obesity-related lipid accumulation and low-grade chronic inflammation.

scholarly journals Role of Gut Microbiota and Their Metabolites on Atherosclerosis, Hypertension and Human Blood Platelet Function: A Review

2020 ◽  
Author(s):  
Asim K Duttaroy
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Human Blood ◽  
Blood Platelets ◽  
Strong Association ◽  
Plasma Lipid ◽  
Blood Platelet ◽  
Short Chain Fatty Acids ◽  
Cardiac Events ◽  
Cvd Risk

Emerging data have demonstrated a strong association between the gut microbiota and the development of cardiovascular disease (CVD) risk factors such as atherosclerosis, inflammation, obesity, insulin resistance, platelet hyperactivity, and plasma lipid abnormalities. Several studies in humans and animal models have demonstrated an association between gut microbial metabolites, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, and bile acid metabolites, amino acid breakdown products, with CVD. Human blood platelets are a critical contributor to the hemostatic process. Besides, these blood cells play a crucial role in developing atherosclerosis and, finally, contribute to cardiac events. Since the TMAO, and other metabolites of the gut microbiota, are associated with platelet hyperactivity, lipid disorders, and oxidative stress, the diet-gut microbiota interactions have become an important research area in the cardiovascular field. Platelets became hyperactive in people with diabetes mellitus, sedentary lifestyle, obesity, and insulin resistance and exhibited increased sensitivity at a baseline level and in response to agonists, ultimately contributing to increased aggregation plaque development. In addition to these factors, TMAO also contributes to platelet hyperactivity. Several approaches are now suggested to reduce plasma TMAO levels, such as microbiota modulation using probiotics, prebiotics, and oral broad-spectrum antibiotics. This review describes the association between microbiota-derived metabolites and CVD development.

scholarly journals Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
M. Nazmul Huda ◽  
Myungsuk Kim ◽  
Brian J. Bennett
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Disease Status ◽  
Short Chain Fatty Acids ◽  
Host Cells ◽  
Low Grade ◽  
Microbial Metabolites ◽  
Microbial Composition

Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.

scholarly journals Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jun-Ke Wang ◽  
Shu-Kun Yao
Keyword(s):  
Gut Microbiota ◽  
Peptide Yy ◽  
Strong Association ◽  
Gut Hormones ◽  
Functional Constipation ◽  
Short Chain Fatty Acids ◽  
Enteric Neurons ◽  
Slow Transit Constipation ◽  
Research Strategies ◽  
Transit Constipation

Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.

scholarly journals Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3041
Author(s):  
Chien-Ning Hsu ◽  
Chih-Yao Hou ◽  
Chien-Te Lee ◽  
Guo-Ping Chang-Chien ◽  
Sufan Lin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Adult Male ◽  
Therapeutic Potential ◽  
Environmental Pollutants ◽  
Renin Angiotensin System ◽  
Short Chain Fatty Acids ◽  
Male Rat ◽  
Sprague Dawley ◽  
Α Diversity ◽  
Pregnancy And Lactation

Maternal exposure to environmental pollutants affects fetal development, which can result in hypertension in adulthood. Gut microbiota-derived metabolite trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and short chain fatty acids (SCFAs) have been associated with hypertension. We tested a hypothesis that maternal 3,3-Dimethyl-1-butanol (DMB, a TMA inhibitor) therapy prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure-induced hypertension in adult offspring relevant to alterations of gut microbiota-derived metabolites, the mediation of aryl hydrocarbon receptor (AHR) signaling, and the renin-angiotensin system (RAS). Pregnant Sprague-Dawley rats were given weekly oral dose of TCDD 200 ng/kg for four doses (T), 1% DMB in drinking water (D), TCDD + DMB (TD), or vehicle (C) in pregnancy and lactation periods. Male progeny (n = 8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused hypertension in adult male offspring coinciding with reduced α-diversity, increased the Firmicutes to Bacteroidetes ratio, less abundant beneficial bacteria, impaired SCFA receptors’ expression, the activation of AHR signaling, and the aberrant activation of the RAS. Treatment with DMB during pregnancy and lactation rescued hypertension induced by perinatal TCDD exposure. This was accompanied by reshaping gut microbiota, mediating TMA-TMAO metabolic pathway, increasing acetic acid and its receptors, and restoring the AHR and RAS pathway. Our data provide new insights into the therapeutic potential of DMB, a microbiome-based metabolite treatment, for the prevention of hypertension of developmental origins.

scholarly journals Gut Microbiota Composition and Metabolites as the new Determinants of Cardiovascular Pathology Development

2020 ◽  
Vol 16 (2) ◽  
pp. 277-285 ◽  
Author(s):  
O. M. Drapkina ◽  
A. N. Kaburova
Keyword(s):  
Cardiovascular Risk ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Short Chain Fatty Acids ◽  
Noncommunicable Diseases ◽  
Future Perspective ◽  
Low Grade ◽  
Microbiota Composition ◽  
Gut Microbiota Composition ◽  
Secondary Bile Acids

Chronic noncommunicable diseases represent one of the key medical problems of the XXI century. In this group cardiovascular diseases (CVD) are known to be the leading cause of death which pathogenesis still has the potential to be more profoundly revealed in order to discover its yet unknown but essential factors. The last decades are marked by the active investigation into the gut bacterial role in the initiation and progression of CVD. The result of this investigation has been the appreciation of microbiome as the potentially new cardiovascular risk factor. The development of sequencing techniques, together with bioinformatics analysis allowed the scientists to intensively broaden the understanding of the gut microbiota composition and functions of its metabolites in maintaining the health and the development of atherosclerosis, arterial hypertension and heart failure. The interaction between macro- and microorganisms is mediated through the variety of pathways, among which the key players are thought to be trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA) and secondary bile acids. TMAO is known due to its role in atherosclerosis development and the increase in major cardiovascular events. In the majority of research SCFA and secondary bile acids have demonstrated protective role in CVD. The great attention is being paid to the role of lipopolysaccharide of gram negative bacteria in the development of systemic low-grade inflammation due to the metabolic endotoxemia which contributes to the progression of CVD. The described interactions draw attention to the opportunity to influence on the certain mechanisms of CVD pathogenesis through the modulation of microbiota composition and function. The review is aimed at highlighting the current data about the mechanisms by which the gut microbiota and its metabolites may increase cardiovascular risk and events rate as well as discussing the existing results and future perspective of bacterial systemic effects modulation.

scholarly journals High-fiber diets attenuate emphysema development via modulation of gut microbiota and metabolism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoon Ok Jang ◽  
Ock-Hwa Kim ◽  
Su Jung Kim ◽  
Se Hee Lee ◽  
Sunmi Yun ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Fiber ◽  
Therapeutic Potential ◽  
Treatment Plan ◽  
Short Chain Fatty Acids ◽  
High Fiber ◽  
Microbial Dysbiosis ◽  
Dietary Nutrients ◽  
Fiber Diet ◽  
High Fiber Diet

AbstractDietary fiber functions as a prebiotic to determine the gut microbe composition. The gut microbiota influences the metabolic functions and immune responses in human health. The gut microbiota and metabolites produced by various dietary components not only modulate immunity but also impact various organs. Although recent findings have suggested that microbial dysbiosis is associated with several respiratory diseases, including asthma, cystic fibrosis, and allergy, the role of microbiota and metabolites produced by dietary nutrients with respect to pulmonary disease remains unclear. Therefore, we explored whether the gut microbiota and metabolites produced by dietary fiber components could influence a cigarette smoking (CS)-exposed emphysema model. In this study, it was demonstrated that a high-fiber diet including non-fermentable cellulose and fermentable pectin attenuated the pathological changes associated with emphysema progression and the inflammatory response in CS-exposed emphysema mice. Moreover, we observed that different types of dietary fiber could modulate the diversity of gut microbiota and differentially impacted anabolism including the generation of short-chain fatty acids, bile acids, and sphingolipids. Overall, the results of this study indicate that high-fiber diets play a beneficial role in the gut microbiota-metabolite modulation and substantially affect CS-exposed emphysema mice. Furthermore, this study suggests the therapeutic potential of gut microbiota and metabolites from a high-fiber diet in emphysema via local and systemic inflammation inhibition, which may be useful in the development of a new COPD treatment plan.

Sign in / Sign up

Export Citation Format

Share Document