scholarly journals Caloric Restriction Remodels Energy Metabolic Pathways of Gut Microbiota and Promotes Host Autophagy

2020 ◽  
Author(s):  
Yuping Yang ◽  
Shaoqiu Chen ◽  
Yumin Liu ◽  
Yuanlong Hou ◽  
Xie Xie ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Pathways ◽  
Glyoxylate Cycle ◽  
Intestinal Flora ◽  
Tca Cycle ◽  
Probiotic Bacteria ◽  
Host Liver ◽  
Host Health ◽  
Microbial Symbiosis ◽  
First Time

AbstractCalorie restriction (CR) can improve the metabolic balance of adults and elevate the relative abundance of probiotic bacteria in the gut while promoting longevity. However, the interaction between remodeled intestinal flora and metabolic improvement, as well as the mechanism for probiotic bacterial increase, are still unclear. In this study, using a metabolomics platform, we demonstrate for the first time, that CR leads to increased levels of malate and its related metabolites in biological samples. Next, we investigated the effects of CR on the gut microbial genome and the expression of mRNA related to energy metabolism which revealed a partially elevated TCA cycle and a subsequently promoted glyoxylate cycle, from which large amounts of malate can be produced to further impact malate related pathways in the host liver. Through the identification of key “hungry” metabolites produced by the gut microbiota that function in the promotion of autophagy in the host, further insight has been gained about a functional metabolic network important for both host-microbial symbiosis and maintenance of host health.

scholarly journals Biotransformation of Timosaponin BII into Seven Characteristic Metabolites by the Gut Microbiota

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3861
Author(s):  
Guo-Ming Dong ◽  
Hang Yu ◽  
Li-Bin Pan ◽  
Shu-Rong Ma ◽  
Hui Xu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Rat Liver ◽  
Pharmacological Activity ◽  
Liver Homogenate ◽  
Intestinal Flora ◽  
Important Indicator ◽  
Metabolic Characteristics ◽  
Metabolic Behavior ◽  
First Time ◽  
Rat Liver Microsome

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.

scholarly journals Comprehensive Plasma Metabolomic Profile of Patients with Advanced Neuroendocrine Tumors (NETs). Diagnostic and Biological Relevance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2634
Author(s):  
Beatriz Soldevilla ◽  
Angeles López-López ◽  
Alberto Lens-Pardo ◽  
Carlos Carretero-Puche ◽  
Angeles Lopez-Gonzalvez ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Networks ◽  
Tca Cycle ◽  
Metabolomic Profile ◽  
Diagnostic Potential ◽  
The Tca Cycle ◽  
Novel Biomarkers ◽  
Potential Methods ◽  
Clinical Potential ◽  
First Time

Purpose: High-throughput “-omic” technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential. Methods: Plasma samples from 77 NETs and 68 controls were profiled by GC−MS, CE−MS and LC−MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential. Results: We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential. Conclusions: This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research.

scholarly journals The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Zhang ◽  
Yanmei Zhang ◽  
Lu Zeng ◽  
Guowei Chen ◽  
La Zhang ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Diabetic Kidney Disease ◽  
Intestinal Flora ◽  
Clinical Indicators ◽  
Serum Metabolites

Objective: Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related serum metabolites in DKD progression in this study.Methods: Fecal and serum samples obtained from predialysis DKD patients from January 2017 to December 2019 were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Forty-one predialysis patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): the DKD non-ESRD group (eGFR ≥ 15 ml/min/1.73 m2) (n = 22), and the DKD ESRD group (eGFR < 15 ml/min/1.73 m2) (n = 19). The metabolic pathways related to differential serum metabolites were obtained by the KEGG pathway analysis. Differences between the two groups relative to gut microbiota profiles and serum metabolites were investigated, and associations between gut microbiota and metabolite concentrations were assessed. Correlations between clinical indicators and both microbiota-related metabolites and gut microbiota were calculated by Spearman rank correlation coefficient and visualized by heatmap.Results: Eleven different intestinal floras and 239 different serum metabolites were identified between the two groups. Of 239 serum metabolites, 192 related to the 11 different intestinal flora were mainly enriched in six metabolic pathways, among which, phenylalanine and tryptophan metabolic pathways were most associated with DKD progression. Four microbiota-related metabolites in the phenylalanine metabolic pathway [hippuric acid (HA), L-(−)-3-phenylactic acid, trans-3-hydroxy-cinnamate, and dihydro-3-coumaric acid] and indole-3 acetic acid (IAA) in the tryptophan metabolic pathway positively correlated with DKD progression, whereas L-tryptophan in the tryptophan metabolic pathway had a negative correlation. Intestinal flora g_Abiotrophia and g_norank_f_Peptococcaceae were positively correlated with the increase in renal function indicators and serum metabolite HA. G_Lachnospiraceae_NC2004_Group was negatively correlated with the increase in renal function indicators and serum metabolites [L-(−)-3-phenyllactic acid and IAA].Conclusions: This study highlights the interaction among gut microbiota, serum metabolites, and clinical indicators in predialysis DKD patients, and provides new insights into the role of gut microbiota and microbiota-related serum metabolites that were enriched in the phenylalanine and tryptophan metabolic pathways, which correlated with the progression of DKD.

scholarly journals Rubidium chloride modulated the fecal microbiota community in mice

2020 ◽  
Author(s):  
Qian Chen ◽  
Zhiguo He ◽  
Yuting Zhuo ◽  
Shuzhen Li ◽  
Wenjing Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Community Diversity ◽  
Microbial Composition ◽  
Sulfate Reducing ◽  
Host Health ◽  
Bacterial Microbiome ◽  
Reducing Bacteria ◽  
First Time ◽  
The Relationship

Abstract Background: The microbiota plays an important role in host health. Although rubidium (Rb) has been used to study for depression and cancers, the interaction between microbial commensals and Rb is still unexplored. To gain the knowledge of the relationship between Rb and microbes, 51 mice receiving RbCl-based treatment and 13 untreated mice were evaluated of their characteristics and bacterial microbiome changes.Results: The 16S ribosomal RNA gene sequencing of feces showed RbCl generally maintained fecal microbial community diversity, while the shifts in fecal microbial composition were apparent after RbCl exposure for the first time. RbCl significantly enhanced the abundances of Rikenellaceae, Alistipes, Clostridium XlVa and sulfate-reducing bacteria including Deltaproteobacteria, Desulfovibrionales, Desulfovibrionaceae and Desulfovibrio. While, RbCl significantly inhibited the abundances of Tenericutes, Mollicutes, Anaeroplasmatales, Anaeroplasmataceae and Anaeroplasma lineages. Besides, with regarding to the composition of archaea, RbCl significantly enhanced the abundances of Crenarchaeota, Thermoprotei, Sulfolobales, Sulfolobaceae and Sulfolobus lineages. Conclusions: These results revealed that enrichments of Clostridium XlVa and Alistipes could affect the levels of serotonin, a critical signaling molecule of brain-gut-microbiota axis. Therefore, anticancer and anti-depressant effects of RbCl might be partly mediated by modifying brain-gut-microbiota axis.

scholarly journals Gut Microbiota, Combined with Metabolomics, Reveals the Mechanism of Curcumol on Liver Fibrosis in Mice

2022 ◽  
Author(s):  
Yang Zheng ◽  
Jiahui Wang ◽  
Jiaru Wang ◽  
Ruizhu Jiang ◽  
Tianjian Liang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Gut Microbiota ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Intestinal Flora ◽  
Pathological Process ◽  
Arachidonic Acid Metabolism ◽  
Liver Inflammation ◽  
16S Rrna Analysis ◽  
The Relationship

Abstract Background:Liver fibrosis is a reversible pathological process, and its prevention and treatment are of great significance to patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and plasma metabolomics to explore the mechanism of curcumol’s effect on liver fibrosis in mice. The results will help to clarify the relationship between the gut microbiota and metabolites in the process of liver fibrosis.Results:Molecular biological testing found that curcumol could significantly improve the pathological changes of liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol’s anti-hepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2.Conclusions:When liver fibrosis occurs, the intestinal flora and metabolic network will be altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby regulating liver inflammation.

Synthesis and Breakdown of the Universal Precursors to Biological Metabolism Promoted by Ferrous Iron

2018 ◽  
Author(s):  
Kamila B. Muchowska ◽  
Sreejith Jayasree VARMA ◽  
Joseph Moran
Keyword(s):  
Amino Acids ◽  
Chemical Reaction ◽  
Metabolic Pathways ◽  
Ferrous Iron ◽  
Reaction Network ◽  
Tca Cycle ◽  
Chemical Reaction Network ◽  
Metabolic Precursors ◽  
Tca Cycle Intermediates

How core biological metabolism initiated and why it uses the intermediates, reactions and pathways that it does remains unclear. Life builds its molecules from CO<sub>2 </sub>and breaks them down to CO<sub>2 </sub>again through the intermediacy of just five metabolites that act as the hubs of biochemistry. Here, we describe a purely chemical reaction network promoted by Fe<sup>2+ </sup>in which aqueous pyruvate and glyoxylate, two products of abiotic CO<sub>2 </sub>reduction, build up nine of the eleven TCA cycle intermediates, including all five universal metabolic precursors. The intermediates simultaneously break down to CO<sub>2 </sub>in a life-like regime resembling biological anabolism and catabolism. Introduction of hydroxylamine and Fe<sup>0 </sup>produces four biological amino acids. The network significantly overlaps the TCA/rTCA and glyoxylate cycles and may represent a prebiotic precursor to these core metabolic pathways.

Microencapsulation: A Prospective to Protect Probiotics

2020 ◽  
Vol 16 (6) ◽  
pp. 891-899 ◽  
Author(s):  
Wissam Zam
Keyword(s):  
Gastrointestinal Tract ◽  
Food Industry ◽  
Health Benefits ◽  
Probiotic Bacteria ◽  
Bacterial Cells ◽  
Beneficial Effects ◽  
Host Health ◽  
Resistant Strains ◽  
Selection Of

Probiotics are viable microorganisms widely used for their claimed beneficial effects on the host health. A wide number of researchers proved that the intake of probiotic bacteria has numerous health benefits which created a big market of probiotic foods worldwide. The biggest challenge in the development of these products is to maintain the viability of bacterial cells during the storage of the product as well as throughout the gastrointestinal tract transit after consumption, so that the claimed health benefits can be delivered to the consumer. Different approaches have been proposed for increasing the resistance of these sensitive microorganisms, including the selection of resistant strains, incorporation of micronutrients, and most recently the use of microencapsulation techniques. Microencapsulation has resulted in enhancing the viability of these microorganisms which allows its wide use in the food industry. In this review, the most common techniques used for microencapsulation of probiotics will be presented, as well as the most usual microcapsule shell materials.

scholarly journals The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 762
Author(s):  
Edward V. Prochownik ◽  
Huabo Wang
Keyword(s):  
Metabolic Pathways ◽  
Redox State ◽  
Pyruvate Dehydrogenase Complex ◽  
Tca Cycle ◽  
Vascular Supply ◽  
Extrinsic Factors ◽  
The Tca Cycle ◽  
Initial Substrate ◽  
Numerous Cell ◽  
Bio Synthesis

Pyruvate occupies a central metabolic node by virtue of its position at the crossroads of glycolysis and the tricarboxylic acid (TCA) cycle and its production and fate being governed by numerous cell-intrinsic and extrinsic factors. The former includes the cell’s type, redox state, ATP content, metabolic requirements and the activities of other metabolic pathways. The latter include the extracellular oxygen concentration, pH and nutrient levels, which are in turn governed by the vascular supply. Within this context, we discuss the six pathways that influence pyruvate content and utilization: 1. The lactate dehydrogenase pathway that either converts excess pyruvate to lactate or that regenerates pyruvate from lactate for use as a fuel or biosynthetic substrate; 2. The alanine pathway that generates alanine and other amino acids; 3. The pyruvate dehydrogenase complex pathway that provides acetyl-CoA, the TCA cycle’s initial substrate; 4. The pyruvate carboxylase reaction that anaplerotically supplies oxaloacetate; 5. The malic enzyme pathway that also links glycolysis and the TCA cycle and generates NADPH to support lipid bio-synthesis; and 6. The acetate bio-synthetic pathway that converts pyruvate directly to acetate. The review discusses the mechanisms controlling these pathways, how they cross-talk and how they cooperate and are regulated to maximize growth and achieve metabolic and energetic harmony.

scholarly journals Itaconate Alters Succinate and Coenzyme A Metabolism via Inhibition of Mitochondrial Complex II and Methylmalonyl-CoA Mutase

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 117
Author(s):  
Thekla Cordes ◽  
Christian M. Metallo
Keyword(s):  
Amino Acid ◽  
Metabolic Pathways ◽  
Mammalian Cells ◽  
Coenzyme A ◽  
Cultured Cells ◽  
Tca Cycle ◽  
Regulatory Function ◽  
Reversible Inhibitor ◽  
Complex Ii ◽  
Branched Chain

Itaconate is a small molecule metabolite that is endogenously produced by cis-aconitate decarboxylase-1 (ACOD1) in mammalian cells and influences numerous cellular processes. The metabolic consequences of itaconate in cells are diverse and contribute to its regulatory function. Here, we have applied isotope tracing and mass spectrometry approaches to explore how itaconate impacts various metabolic pathways in cultured cells. Itaconate is a competitive and reversible inhibitor of Complex II/succinate dehydrogenase (SDH) that alters tricarboxylic acid (TCA) cycle metabolism leading to succinate accumulation. Upon activation with coenzyme A (CoA), itaconyl-CoA inhibits adenosylcobalamin-mediated methylmalonyl-CoA (MUT) activity and, thus, indirectly impacts branched-chain amino acid (BCAA) metabolism and fatty acid diversity. Itaconate, therefore, alters the balance of CoA species in mitochondria through its impacts on TCA, amino acid, vitamin B12, and CoA metabolism. Our results highlight the diverse metabolic pathways regulated by itaconate and provide a roadmap to link these metabolites to potential downstream biological functions.

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