scholarly journals Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2514
Author(s):  
Alicia Arredondo Eve ◽  
Xiaoji Liu ◽  
Yanling Wang ◽  
Michael J. Miller ◽  
Elizabeth H. Jeffery ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
De Novo ◽  
Plasma Metabolites ◽  
Glutathione Metabolism ◽  
Glutathione Synthesis ◽  
16S Sequencing ◽  
Hepatic Glutathione ◽  
Liver Health ◽  
Plasma Metabolite ◽  
Diet And Lifestyle

Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC–MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut–liver axis health.

scholarly journals An online atlas of human plasma metabolite signatures of gut microbiome composition

2021 ◽  
Author(s):  
Koen F. Dekkers ◽  
Sergi Sayols-Baixeras ◽  
Gabriel Baldanzi ◽  
Christoph Nowak ◽  
Ulf Hammar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
High Performance ◽  
Alpha Diversity ◽  
Plasma Metabolites ◽  
Uremic Toxin ◽  
Metagenomic Sequencing ◽  
Microbiome Composition ◽  
Plasma Metabolite

The human gut microbiota produces a variety of small compounds, some of which enter the bloodstream and impact host health. Conversely, various exogenous nutritional and pharmaceutical compounds affect the gut microbiome composition before entering circulation. Characterization of the gut microbiota—host plasma metabolite interactions is an important step towards understanding the effects of the gut microbiota on human health. However, studies involving large and deeply phenotyped cohorts that would reveal such meaningful interactions are scarce. Here, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for detailed characterization of the fecal microbiota and plasma metabolome, respectively, of 8,584 participants invited at age 50 to 64 of the Swedish CArdioPulmonary bioImage Study (SCAPIS). After adjusting for multiple comparisons, we identified 1,008 associations between species alpha diversity and plasma metabolites, and 318,944 associations between specific gut metagenomic species and plasma metabolites. The gut microbiota explained up to 50% of the variance of individual plasma metabolites (mean of 4.7%). We present all results as the searchable association atlas "GUTSY" as a rich resource for mining associations, and exemplify the potential of the atlas by presenting novel associations between oral medication and the gut microbiome, and microbiota species strongly associated with levels of the uremic toxin p-cresol sulfate. The association atlas can be used as the basis for targeted studies of perturbation of specific bacteria and for identification of candidate plasma biomarkers of gut flora composition.

scholarly journals Exocrine Pancreatic Function Modulates Plasma Metabolites Through Changes in Gut Microbiota Composition

2021 ◽  
Author(s):  
Maik Pietzner ◽  
Kathrin Budde ◽  
Malte Rühlemann ◽  
Henry Völzke ◽  
Georg Homuth ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Population Based ◽  
Exocrine Pancreatic Function ◽  
Pancreatic Function ◽  
Plasma Metabolites ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microbiota Composition ◽  
Plasma Metabolite ◽  
Gut Microbiota Composition

Abstract Purpose Exocrine pancreatic function is critically involved in regulating the gut microbiota composition. At the same time, its impairment acutely affects human metabolism. How these 2 roles are connected is unknown. We studied how the exocrine pancreas contributes to metabolism via modulation of gut microbiota. Design Fecal samples were collected in 2226 participants of the population-based Study of Health in Pomerania (SHIP/SHIP-TREND) to determine exocrine pancreatic function (pancreatic elastase enzyme-linked immunosorbent assay) and intestinal microbiota profiles (16S ribosomal ribonucleic acid gene sequencing). Plasma metabolite levels were determined by mass spectrometry. Results Exocrine pancreatic function was associated with changes in the abundance of 28 taxa and, simultaneously, with those of 16 plasma metabolites. Mediation pathway analysis revealed that a significant component of how exocrine pancreatic function affects the blood metabolome is mediated via gut microbiota abundance changes, most prominently, circulating serotonin and lysophosphatidylcholines. Conclusion These results imply that the effect of exocrine pancreatic function on intestinal microbiota composition alters the availability of microbial-derived metabolites in the blood and thus directly contributes to the host metabolic changes associated with exocrine pancreatic dysfunction.

scholarly journals Connection Between BMI-Related Plasma Metabolite Profile and Gut Microbiota

2018 ◽  
Vol 103 (4) ◽  
pp. 1491-1501 ◽  
Author(s):  
Filip Ottosson ◽  
Louise Brunkwall ◽  
Ulrika Ericson ◽  
Peter M Nilsson ◽  
Peter Almgren ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Principal Component ◽  
Metabolite Profile ◽  
Plasma Metabolites ◽  
Least Squares Regression ◽  
Metabolic Functions ◽  
Plasma Metabolome ◽  
Branched Chain ◽  
Plasma Metabolite

Abstract Context Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma metabolome might reflect differences in the gut microbiome. Objective To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota. Design Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography–mass spectrometry. Gut microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region) in fecal samples of 674 study participants. Results BMI was associated with 19 metabolites (P < 0.001 for all), of which glutamate provided the strongest direct association (P = 5.2e-53). By orthogonal partial least squares regression, a metabolite principal component predictive of BMI was constructed (PCBMI). In addition to glutamate, PCBMI was dominated by branched-chain amino acids (BCAAs) and related metabolites. Four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) were associated with both BMI and PCBMI (P < 8.0e-4 for all). When simultaneously regressing PCBMI and metabolite-associated gut bacteria against BMI, only PCBMI remained statistically significant. Conclusions We discovered associations between four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) and BMI-predictive plasma metabolites, including glutamate and BCAAs. Thus, these metabolites could be mediators between gut microbiota and obesity, pointing to potential future opportunities for targeting the gut microbiota in prevention of obesity.

scholarly journals Detection of Dysbiosis and Increased Intestinal Permeability in Brazilian Patients with Relapsing–Remitting Multiple Sclerosis

2021 ◽  
Vol 18 (9) ◽  
pp. 4621
Author(s):  
Felipe Papa Pellizoni ◽  
Aline Zazeri Leite ◽  
Nathália de Campos Rodrigues ◽  
Marcelo Jordão Ubaiz ◽  
Marina Ignácio Gonzaga ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Intestinal Permeability ◽  
Dietary Habits ◽  
Dietary Interventions ◽  
Chi Square ◽  
16S Sequencing ◽  
Intestinal Dysbiosis ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Dysbiosis, associated with barrier disruption and altered gut–brain communications, has been associated with multiple sclerosis (MS). In this study, we evaluated the gut microbiota in relapsing–remitting patients (RRMS) receiving disease-modifying therapies (DMTs) and correlated these data with diet, cytokines levels, and zonulin concentrations. Stool samples were used for 16S sequencing and real-time PCR. Serum was used for cytokine determination by flow cytometry, and zonulin quantification by ELISA. Pearson’s chi-square, Mann–Whitney, and Spearman’s correlation were used for statistical analyses. We detected differences in dietary habits, as well as in the gut microbiota in RRMS patients, with predominance of Akkermansia muciniphila and Bacteroides vulgatus and decreased Bifidobacterium. Interleukin-6 concentrations were decreased in treated patients, and we detected an increased intestinal permeability in RRMS patients when compared with controls. We conclude that diet plays an important role in the composition of the gut microbiota, and intestinal dysbiosis, detected in RRMS patients could be involved in increased intestinal permeability and affect the clinical response to DTMs. The future goal is to predict therapeutic responses based on individual microbiome analyses (personalized medicine) and propose dietary interventions and the use of probiotics or other microbiota modulators as adjuvant therapy to enhance the therapeutic efficacy of DMTs.

scholarly journals Regulation of intracellular glutathione levels in erythrocytes infected with chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

2002 ◽  
Vol 368 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Svenja MEIERJOHANN ◽  
Rolf D. WALTER ◽  
Sylke MÜLLER
Keyword(s):  
Oxidative Stress ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Differential Susceptibility ◽  
Protozoan Parasite ◽  
Chloroquine Resistance ◽  
Glutathione Metabolism ◽  
Glutathione Synthesis ◽  
Intracellular Glutathione ◽  
Glutamylcysteine Synthetase

Malaria is one of the most devastating tropical diseases despite the availability of numerous drugs acting against the protozoan parasite Plasmodium in its human host. However, the development of drug resistance renders most of the existing drugs useless. In the malaria parasite the tripeptide glutathione is not only involved in maintaining an adequate intracellular redox environment and protecting the cell against oxidative stress, but it has also been shown that it degrades non-polymerized ferriprotoporphyrin IX (FP IX) and is thus implicated in the development of chloroquine resistance. Glutathione levels in Plasmodium-infected red blood cells are regulated by glutathione synthesis, glutathione reduction and glutathione efflux. Therefore the effects of drugs that interfere with these metabolic processes were studied to establish possible differences in the regulation of the glutathione metabolism of a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodiumfalciparum. Growth inhibition of P. falciparum 3D7 by d,l-buthionine-(S,R)sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (γ-GCS), and by Methylene Blue (MB), an inhibitor of gluta thione reductase (GR), was significantly more pronounced than inhibition of P.falciparum Dd2 growth by these drugs. These results correlate with the higher levels of total glutathione in P. falciparum Dd2. Short-term incubations of Percoll-enriched trophozoite-infected red blood cells in the presence of BSO, MB and N,N1-bis(2-chloroethyl)-N-nitrosourea and subsequent determinations of γ-GCS activities, GR activities and glutathione disulphide efflux revealed that maintenance of intracellular glutathione in P. falciparum Dd2 is mainly dependent on glutathione synthesis whereas in P. falciparum 3D7 it is regulated via GR. Generally, P. falciparum Dd2 appears to be able to sustain its intracellular glutathione more efficiently than P. falciparum 3D7. In agreement with these findings is the differential susceptibility to oxidative stress of both parasite strains elicited by the glucose/glucose oxidase system.

scholarly journals Metabolic and endocrine changes induced by chronic heatexposure in broiler chickens : biological and endocrinological variables

1996 ◽  
Vol 75 (2) ◽  
pp. 205-216 ◽  
Author(s):  
P. A. Geraert ◽  
J. C. F. Padilha ◽  
S. Guillaumin
Keyword(s):  
Amino Acids ◽  
Ambient Temperature ◽  
Broiler Chickens ◽  
De Novo ◽  
Heat Exposure ◽  
Plasma Corticosterone ◽  
Plasma Metabolites ◽  
Exogenous Insulin ◽  
Plasma Insulin Concentration ◽  
Esterified Fatty Acids

Abstract:The present study was designed to investigate the effect of chronic heat exposure (32° constant) on plasma metabolites and hormone concentrations in broiler chickens. At 2 and 4 weeks of age, fifty-four male Shaver broiler chickens were allocated to one of three treatments: 22°ad lib. feeding (22AL), 32°ad lib. feeding (32AL) and 22°,pair-feeding with the 32AL group (22PF). Ambient temperature was kept constant at either 22 or 32° for 2 weeks. Plasma glucose, triacylglycerols, phospholipids, non-esterified fatty acids (NEFA), individual amino acids, uric acid, insulin, triiodothyronine (T3), thyroxine, corticosterone were determined. Sensitivity to exogenous insulin was also measured at 7 weeks of age. At 4 and 6 weeks of age, i.e. after 2 weeks at high ambient temperature, fasted 32AL chickens displayed similar concentrations of glucose and triacylglycerols to those of 22AL birds. When fed, 32AL chickens exhibited higher plasma levels of glucose and decreased concentrations of NEFAand amino acids. Feed restriction resulted in intermediate values. Concentrations of all plasmafree amino acids were decreased under heat exposure except for aspartic acid, glutamic acid andphenylalanine. At 6 weeks of age, plasma T3 was reduced irrespective of the nutritional state, while plasma corticosterone concentrations were increased in 32AL birds compared with 22AL birds. Heat exposure did not change plasma insulin concentration in either fasted or fed chickens. The 32AL chickens displayed significantly reduced sensitivity to exogenous insulin when fasted,but an enhanced response to insulin when fed, compared with both 22° groups. Such endocrinological changes could stimulate lipid accumulation through increasedde novolipogenesis, reduced lipolysis and enhanced amino acid catabolism under chronic heat exposure.

Toxic Doses of Acetaminophen Suppress Hepatic Glutathione Synthesis in Rats

Hepatology ◽  
2007 ◽  
Vol 2 (1) ◽  
pp. 8S-12S ◽  
Author(s):  
Bernhard H. Lauterburg ◽  
Jerry R. Mitchell
Keyword(s):  
Glutathione Synthesis ◽  
Hepatic Glutathione

scholarly journals Effects of Long-Term Hydrogen Intervention on Plasma Metabolites and Gut Microbiome of Rats in Health Status

2021 ◽  
Author(s):  
Fei Xie ◽  
Xue Jiang ◽  
Yang Yi ◽  
Zi-Jia Liu ◽  
Chen Ma ◽  
...  
Keyword(s):  
Health Status ◽  
Gut Microbiota ◽  
Biological Effects ◽  
Enrichment Analysis ◽  
The Body ◽  
Plasma Metabolites ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Rrna Gene

Abstract The potential for preventive and therapeutic applications of H2 have now been confirmed in various disease. However, the effects of H2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.

scholarly journals Nucleotide Biosynthesis Links Glutathione Metabolism to Ferroptosis Sensitivity

2021 ◽  
Author(s):  
Amy Tarangelo ◽  
Joon Tae Kim ◽  
Jonathan Z Long ◽  
Scott J Dixon
Keyword(s):  
Cell Death ◽  
De Novo ◽  
Apoptotic Cell ◽  
Lipid Peroxides ◽  
Nucleotide Metabolism ◽  
Apoptotic Cell Death ◽  
Death Process ◽  
Glutathione Metabolism ◽  
Dependent Manner ◽  
Nucleotide Synthesis

Nucleotide synthesis is a metabolically demanding process essential for cell division. Several anti-cancer drugs that inhibit nucleotide metabolism induce apoptosis. How inhibition of nucleotide metabolism impacts non-apoptotic cell death is less clear. Here, we report that inhibition of nucleotide metabolism by the p53 pathway is sufficient to suppress the non-apoptotic cell death process of ferroptosis. Mechanistically, stabilization of wild-type p53 and induction of the p53 target gene CDKN1A (p21) leads to decreased expression of the ribonucleotide reductase (RNR) subunits RRM1 and RRM2. RNR is the rate-limiting enzyme of de novo nucleotide synthesis that reduces ribonucleotides to deoxyribonucleotides in a glutathione-dependent manner. Direct inhibition of RNR conserves glutathione which can then be used to limit the accumulation of toxic lipid peroxides, preventing the onset of ferroptosis. These results support a mechanism linking p53-dependent regulation of nucleotide metabolism to non-apoptotic cell death.

scholarly journals The effects of gestational age on the composition and predicted function of gut microbiota in neonates and early infants

2021 ◽  
Vol 12 (2) ◽  
pp. 567-573
Author(s):  
Kaiyu Pan ◽  
Lianfang Yu ◽  
Chengyue Zhang ◽  
Jianhua Zhan ◽  
Rongliang Tu
Keyword(s):  
Gut Microbiota ◽  
Gestational Age ◽  
Full Term ◽  
Rrna Gene ◽  
Delivery Mode ◽  
16S Sequencing ◽  
Α Diversity ◽  
Preterm Group ◽  
Stool Samples ◽  
Predicted Function

Gut microbiota can influence cell differentiation, metabolism, and immune function and is key for the normal development and future health of early infants. Several factors have been reported to be related to the microbiota composition of neonates, such as gestational age, delivery mode, feeding method, antibiotics consumption, and ethnicity, among others. So we investigated the relationship between gestational age and the composition and predicted function of the gut microbiota of neonates and early infants by sequencing the 16S rRNA gene present in stool samples obtained from 100 prospectively enrolled full-term and preterm newborns. In the 3-day-old neonates samples, the prominent genera in the full-term group were Escherichia-Shigella, Streptococcus, Bifidobacterium, and Bacteroides, while in the preterm group, Staphylococcus, Streptococcus, Escherichia-Shigella and Clostridium were the most abundant genera identified. There were statistical difference between two groups(P<0.05). Moreover, the predominant genera in the full-term group were Bifidobacterium, Lactobacillus, Bacteroides, and Clostridium , whereas the main genera in the preterm group were Escherichia-Shigella, Clostridium, Bifidobacterium and Bacteroides, in stool samples from 30-42-day-old infants. We found the α-diversity in 3-day-old group was significantly lower than in the 30-42-day-old group whether it’s full-term or preterm (P<0.001). Functional inference analysis revealed higher levels of biodegradation and metabolism of carbohydrates, vitamins in the full-term group than in the preterm group, both in neonates and early infants, which may contribute to the stability of the microbiota in the full-term group. There were significant differences in the composition and predicted function of the gut microbiota of early infants due to gestational age. The 16S sequencing technology was an effective and reliable tool in the detection of gut microbiota in early infants.

Sign in / Sign up

Export Citation Format

Share Document