scholarly journals Gut Microbial Associations to Plasma Metabolites Linked to Cardiovascular Phenotypes and Risk

2019 ◽  
Vol 124 (12) ◽  
pp. 1808-1820 ◽  
Author(s):  
Alexander Kurilshikov ◽  
Inge C.L. van den Munckhof ◽  
Lianmin Chen ◽  
Marc J. Bonder ◽  
Kiki Schraa ◽  
...  

Rationale: Altered gut microbial composition has been linked to cardiovascular diseases (CVDs), but its functional links to host metabolism and immunity in relation to CVD development remain unclear. Objectives: To systematically assess functional links between the microbiome and the plasma metabolome, cardiometabolic phenotypes, and CVD risk and to identify diet-microbe-metabolism-immune interactions in well-documented cohorts. Methods and Results: We assessed metagenomics-based microbial associations between 231 plasma metabolites and microbial species and pathways in the population-based LLD (Lifelines DEEP) cohort (n=978) and a clinical obesity cohort (n=297). After correcting for age, sex, and body mass index, the gut microbiome could explain ≤11.1% and 16.4% of the variation in plasma metabolites in the population-based and obesity cohorts, respectively. Obese-specific microbial associations were found for lipid compositions in the VLDL, IDL, and LDL lipoprotein subclasses. Bacterial L-methionine biosynthesis and a Ruminococcus species were associated to cardiovascular phenotypes in obese individuals, namely atherosclerosis and liver fat content, respectively. Integration of microbiome-diet-inflammation analysis in relation to metabolic risk score of CVD in the population cohort revealed 48 microbial pathways associated to CVD risk that were largely independent of diet and inflammation. Our data also showed that plasma levels rather than fecal levels of short-chain fatty acids were relevant to inflammation and CVD risk. Conclusions: This study presents the largest metagenome-based association study on plasma metabolism and microbiome relevance to diet, inflammation, CVD risk, and cardiometabolic phenotypes in both population-based and clinical obesity cohorts. Our findings identified novel bacterial species and pathways that associated to specific lipoprotein subclasses and revealed functional links between the gut microbiome and host health that provide a basis for developing microbiome-targeted therapy for disease prevention and treatment.

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Shasha Xiang ◽  
Kun Ye ◽  
Mian Li ◽  
Jian Ying ◽  
Huanhuan Wang ◽  
...  

Abstract Background Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts. Results In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate. Conclusions Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs.


2021 ◽  
Author(s):  
Josue Castro Mejia ◽  
Bekzod Khakimov ◽  
Mads Lind ◽  
Eva Garne ◽  
Petronela Paulova ◽  
...  

Increasing evidence indicates that the gut microbiome (GM) plays an important role in the etiology of dyslipidemia. To date, however, no in depth characterization of the associations between GM and its metabolic attributes with deep profiling of lipoproteins distributions (LPD) among healthy individuals has been conducted. To determine associations and contributions of GM composition and its cofactors with distribution profiles of lipoprotein subfractions, we studied blood plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 healthy Danish subjects aged 19-89 years. Stratification of LPD segregated subjects into three clusters of profiles that reflected differences in the lipoprotein subclasses, corresponded well with limits of recommended levels of main lipoprotein fractions and were largely explained by host characteristics such as age and body mass index. Higher levels of HDL, particularly driven by large subfractions (HDL2a and HDL2b), were associated with a higher relative abundance of Ruminococcaceae and Christensenellaceae. Increasing levels of total cholesterol and LDL, which were primarily associated with large 1 and 2 subclasses, were positively associated with Lachnospiraceae and Coriobacteriaceae, and negatively with Bacteroidaceae and Bifidobacteriaceae. Metagenome sequencing showed a higher abundance of genes involved in the biosynthesis of multiple B-vitamins and SCFA metabolism among subjects with healthier LPD profiles. Metagenomic assembled genomes (MAGs) affiliated mainly to Eggerthellaceae and Clostridiales were identified as the contributors of these genes and whose relative abundance correlated positively with larger subfractions of HDL. The results of this study demonstrate that remarkable differences in composition and metabolic traits of the GM are associated with variations in LPD among healthy subjects. Findings from this study provide evidence for GM considerations in future research aiming to shade light on mechanisms of the GM - dyslipidemia axis.


Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1613 ◽  
Author(s):  
Ronald Hills ◽  
Benjamin Pontefract ◽  
Hillary Mishcon ◽  
Cody Black ◽  
Steven Sutton ◽  
...  

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.


2021 ◽  
Author(s):  
Artur Trzebny ◽  
Anna Slodkowicz-Kowalska ◽  
Johanna Björkroth ◽  
Miroslawa Dabert

AbstractThe animal gut microbiota consist of many different microorganisms, mainly bacteria, but archaea, fungi, protozoans, and viruses may also be present. This complex and dynamic community of microorganisms may change during parasitic infection. In the present study, we investigated the effect of the presence of microsporidians on the composition of the mosquito gut microbiota and linked some microbiome taxa and functionalities to infections caused by these parasites. We characterised bacterial communities of 188 mosquito females, of which 108 were positive for microsporidian DNA. To assess how bacterial communities change during microsporidian infection, microbiome structures were identified using 16S rRNA microbial profiling. In total, we identified 46 families and four higher taxa, of which Comamonadaceae, Enterobacteriaceae, Flavobacteriaceae and Pseudomonadaceae were the most abundant mosquito-associated bacterial families. Our data suggest that the mosquito gut microbial composition varies among host species. In addition, we found a correlation between the microbiome composition and the presence of microsporidians. The prediction of metagenome functional content from the 16S rRNA gene sequencing suggests that microsporidian infection is characterised by some bacterial species capable of specific metabolic functions, especially the biosynthesis of ansamycins and vancomycin antibiotics and the pentose phosphate pathway. Moreover, we detected a positive correlation between the presence of microsporidian DNA and bacteria belonging to Spiroplasmataceae and Leuconostocaceae, each represented by a single species, Spiroplasma sp. PL03 and Weissella cf. viridescens, respectively. Additionally, W. cf. viridescens was observed only in microsporidian-infected mosquitoes. More extensive research, including intensive and varied host sampling, as well as determination of metabolic activities based on quantitative methods, should be carried out to confirm our results.


2019 ◽  
Vol 13 (11) ◽  
pp. 1439-1449 ◽  
Author(s):  
Marjolein A Y Klaassen ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Jingyuan Fu ◽  
Cisca Wijmenga ◽  
...  

Abstract Background and Aims Crohn’s disease [CD] is a chronic inflammatory disorder of the gastrointestinal tract characterised by alternating periods of exacerbation and remission. We hypothesised that changes in the gut microbiome are associated with CD exacerbations, and therefore aimed to correlate multiple gut microbiome features to CD disease activity. Methods Faecal microbiome data generated using whole-genome metagenomic shotgun sequencing of 196 CD patients were of obtained from the 1000IBD cohort [one sample per patient]. Patient disease activity status at time of sampling was determined by re-assessing clinical records 3 years after faecal sample production. Faecal samples were designated as taken ‘in an exacerbation’ or ‘in remission’. Samples taken ‘in remission’ were further categorised as ‘before the next exacerbation’ or ‘after the last exacerbation’, based on the exacerbation closest in time to the faecal production date. CD activity was correlated with gut microbial composition and predicted functional pathways via logistic regressions using MaAsLin software. Results In total, 105 bacterial pathways were decreased during CD exacerbation (false-discovery rate [FDR] <0.1) in comparison with the gut microbiome of patients both before and after an exacerbation. Most of these decreased pathways exert anti-inflammatory properties facilitating the biosynthesis and fermentation of various amino acids [tryptophan, methionine, and arginine], vitamins [riboflavin and thiamine], and short-chain fatty acids [SCFAs]. Conclusions CD exacerbations are associated with a decrease in microbial genes involved in the biosynthesis of the anti-inflammatory mediators riboflavin, thiamine, and folate, and SCFAs, suggesting that increasing the intestinal abundances of these mediators might provide new treatment opportunities. These results were generated using bioinformatic analyses of cross-sectional data and need to be replicated using time-series and wet lab experiments.


2020 ◽  
Author(s):  
Tian Qin ◽  
Jingyuan Fu ◽  
Henkjan J. Verkade

Abstract Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jiawei Wan ◽  
Yanbei Wu ◽  
Quynhchi Pham ◽  
Robert Li ◽  
Liangli Yu ◽  
...  

Abstract Objectives The aim of this study is to evaluate the effects of rice containing different levels of resistant starch on the gut microbiome using a rodent model. Methods Rice with low resistant starch (0.11%), medium resistant starch (1.07%) and high resistant starch (8.61%) were cooked, grounded into powders and used to formulate diet to represent all the carbohydrates in mice diet that consist of low fat (LF, 10 kcal %) or high fat (HF, 39 kcal %). C57BL/6 mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat and low resistant starch diet (LL); (2) high-fat and low resistant starch diet (HL); (3) low-fat and medium resistant starch diet (LM); (4) high-fat and medium resistant starch diet (HM); (5) low-fat and high resistant starch diet (LH); (6) high-fat and high resistant starch diet (HH). Mice were fed with diets for 8 weeks then gut microbiome composition was determined using 16S rDNA sequencing of cecal contents. Results We found that the gut microbiome was significantly different at different levels of resistant starch (P < 0.01) but not at different fat levels. OTU (operational taxonomic unit) richness was reduced in LF and HF high-resistant groups as compared to others. OTU diversity was reduced in LF and HF medium and high-resistant groups as compared to low-resistant groups. Decreased Firmicutes to Bacteroidetes ratio, which related to lower risk of obesity, was observed in mice fed LF and HF high-resistant diet as compared to others. Moreover, at the family level, LF, HF high-resistant diet mainly increased the abundances of Bacteroidaceae and S24_7, the bacteria positively correlated with SCFAs (short-chain fatty acids) levels. We also observed a decrease in abundances of Odoribacteraceae, Rikenellaceae, Lachnospiraceae, Ruminococcaceae and Desulfovibrionaceae in LF and HF high resistant starch group. Desulfovibrionaceae and genus Odoribecter in Odoribacteraceae are reported to be opportunistic pathogens, Lachnospiraceae, Ruminococcaceae, Odoribacteraceae and Rikenellaceae are associated with obesity. Conclusions Overall, our results demonstrated that resistant starch exerted concentration-dependent effect on the gut microbiome in mice which may have protective effect against obesity. Funding Sources USDA, ARS.


2015 ◽  
Vol 6 (1) ◽  
pp. 97-111 ◽  
Author(s):  
U. Etxeberria ◽  
N. Arias ◽  
N. Boqué ◽  
M.T. Macarulla ◽  
M.P. Portillo ◽  
...  

The gastrointestinal tract harbours a ‘superorganism’ called the gut microbiota, which is known to play a crucial role in the onset and development of diverse diseases. This internal ecosystem, far from being a static environment, can be manipulated by diet and dietary components. Feeding animals with high-fat sucrose (HFS) diets entails diet-induced obesity, a model which is usually used in research to mimic the obese phenotype of Western societies. The aim of the present study was to identify gut microbiota dysbiosis and associated metabolic changes produced in male Wistar rats fed a HFS diet for 6 weeks and compare it with the basal microbial composition. For this purpose, DNA extracted from faeces at baseline and after treatment was analysed by amplification of the V4-V6 region of the 16S ribosomal DNA (rDNA) gene using 454 pyrosequencing. Short-chain fatty acids, i.e. acetate, propionate and butyrate, were also evaluated by gas chromatography-mass spectrometry. At the end of the treatment, gut microbiota composition significantly differed at phylum level (Firmicutes, Bacteroidetes and Proteobacteria) and class level (Erisypelotrichi, Deltaproteobacteria, Bacteroidia and Bacilli). Interestingly, the class Clostridia showed a significant decrease after HFS diet treatment, which correlated with visceral adipose tissue, and is likely mediated by dietary carbohydrates. Of particular interest, Clostridium cluster XIVa species were significantly reduced and changes were identified in the relative abundance of other specific bacterial species (Mitsuokella jalaludinii, Eubacterium ventriosum, Clostridium sp. FCB90-3, Prevotella nanceiensis, Clostridium fusiformis, Clostridium sp. BNL1100 and Eubacterium cylindroides) that, in some cases, showed opposite trends to their relative families. These results highlight the relevance of characterising gut microbial population differences at species level and contribute to understand the plausible link between diet and specific gut bacterial species that are able to influence the inflammatory status, intestinal barrier function and obesity development.


mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Yueqiong Ni ◽  
Jun Li ◽  
Gianni Panagiotou

ABSTRACT As diet is considered the major regulator of the gut ecosystem, the overall objective of this work was to demonstrate that a detailed knowledge of the phytochemical composition of food could add to our understanding of observed changes in functionality and activity of the gut microbiota. We used metatranscriptomic data from a human dietary intervention study to develop a network that consists of >400 compounds present in the administered plant-based diet linked to 609 microbial targets in the gut. Approximately 20% of the targeted bacterial proteins showed significant changes in their gene expression levels, while functional and topology analyses revealed that proteins in metabolic networks with high centrality are the most “vulnerable” targets. This global view and the mechanistic understanding of the associations between microbial gene expression and dietary molecules could be regarded as a promising methodological approach for targeting specific bacterial proteins that impact human health. IMPORTANCE It is a general belief that microbiome-derived drugs and therapies will come to the market in coming years, either in the form of molecules that mimic a beneficial interaction between bacteria and host or molecules that disturb a harmful interaction or proteins that can modify the microbiome or bacterial species to change the balance of “good” and “bad” bacteria in the gut microbiome. However, among the numerous factors, what has proven the most influential for modulating the microbial composition of the gut is diet. In line with this, we demonstrate here that a systematic analysis of the interactions between the small molecules present in our diet and the gut bacterial proteome holds great potential for designing dietary interventions to improve human health.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Yoshiki Vázquez-Baeza ◽  
Guo-Chong Chen ◽  
Carmen R. Isasi ◽  
...  

Abstract Background Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos. Results The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus. Conclusions Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.


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