DRAM for distilling microbial metabolism to automate the curation of microbiome function

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 48(16), P. 8883 - 8900

Published: July 22, 2020

Abstract Microbial and viral communities transform the chemistry of Earth's ecosystems, yet specific reactions catalyzed by these biological engines are hard to decode due absence a scalable, metabolically resolved, annotation software. Here, we present DRAM (Distilled Refined Annotation Metabolism), framework translate deluge microbiome-based genomic information into catalog microbial traits. To demonstrate applicability across diverse genomes, evaluated performance on defined, in silico soil community previously published human gut metagenomes. We show that accurately assigned contributions geochemical cycles automated partitioning carbohydrate metabolism at substrate levels. DRAM-v, mode DRAM, established rules identify virally-encoded auxiliary metabolic genes (AMGs), resulting categorization thousands putative AMGs from soils guts. Together DRAM-v provide critical profiling capabilities decipher mechanisms underpinning microbiome function.

Language: Английский

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Free Fatty Acid Receptors in Health and Disease

Physiological Reviews, Journal Year: 2019, Volume and Issue: 100(1), P. 171 - 210

Published: Sept. 5, 2019

Fatty acids are metabolized and synthesized as energy substrates during biological responses. Long- medium-chain fatty derived mainly from dietary triglycerides, short-chain (SCFAs) produced by gut microbial fermentation of the otherwise indigestible fiber, constitute major sources free (FFAs) in metabolic network. Recently, increasing evidence indicates that FFAs serve not only but also natural ligands for a group orphan G protein-coupled receptors (GPCRs) termed acid (FFARs), essentially intertwining metabolism immunity multiple ways, such via inflammation regulation secretion peptide hormones. To date, several FFARs activated various chain lengths have been identified characterized. In particular, FFAR1 (GPR40) FFAR4 (GPR120) long-chain saturated unsaturated acids, while FFAR3 (GPR41) FFAR2 (GPR43) SCFAs, acetate, butyrate, propionate. this review, we discuss recent reports on key physiological functions FFAR-mediated signaling transduction pathways immune We attempt to reveal future research opportunities developing therapeutics disorders.

Language: Английский

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Gut Microbiota and Cardiovascular Disease

Circulation Research, Journal Year: 2020, Volume and Issue: 127(4), P. 553 - 570

Published: July 30, 2020

Fecal microbial community changes are associated with numerous disease states, including cardiovascular (CVD). However, such data merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, transplantation studies, specific microbiota-dependent pathways, and downstream metabolites have all shown to influence host metabolism CVD, sometimes through identified receptors. Multiple metaorganismal pathways (involving both microbe host) impact animal models show striking clinical associations human studies. For example, trimethylamine N-oxide and, recently, phenylacetylglutamine whose blood levels incident risks large-scale Importantly, link these other metabolites/pathways mechanistic model Phenylacetylglutamine, was recently promote adverse phenotypes the via interaction multiple ARs (adrenergic receptors)-a class key receptors that regulate homeostasis. In this review, we summarize recent advances microbiome research related cardiometabolic helped move field forward from associative causative results. We focus on compounds/pathways, attention paid short-chain fatty acids, secondary bile N-oxide, phenylacetylglutamine. also discuss novel therapeutic strategies directly targeting improve outcomes.

Language: Английский

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NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 7, 2020

Abstract Nicotinamide adenine dinucleotide (NAD + ) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells adapt environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation xenobiotics. These effects are mainly achieved by driving effect of NAD on metabolic pathways enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple -dependent enzymes involved physiology either post-synthesis chemical modification DNA, RNA proteins, or releasing second messenger cyclic ADP-ribose (cADPR) NAADP . Prolonged disequilibrium metabolism disturbs physiological functions, resulting diseases diseases, cancer, aging neurodegeneration disorder. In this review, we summarize recent advances our understanding molecular mechanisms -regulated responses stresses, contribution deficiency various via manipulating cellular communication networks potential new avenues for therapeutic intervention.

Language: Английский

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Reappraising the role of inflammation in heart failure

Nature Reviews Cardiology, Journal Year: 2020, Volume and Issue: 17(5), P. 269 - 285

Published: Jan. 22, 2020

Language: Английский

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Inflammation in Heart Failure

Journal of the American College of Cardiology, Journal Year: 2020, Volume and Issue: 75(11), P. 1324 - 1340

Published: March 1, 2020

It has long been observed that heart failure (HF) is associated with measures of systemic inflammation. In recent years, there have significant advancements in our understanding how inflammation contributes to the pathogenesis and progression HF. However, although numerous studies validated association between HF severity prognosis, clinical trials anti-inflammatory therapies proven mostly unsuccessful. On this backdrop emerges yet unmet goal targeting precise phenotypes within syndrome HF; if such definitions can be realized, better roles played by specific inflammatory mediators, expectation targeted may improve prognosis patients whose driven pathobiology. Here, authors describe mechanistic links HF, discuss traditional novel biomarkers, summarize latest evidence from therapies.

Language: Английский

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Pathophysiology of Hypertension

Circulation Research, Journal Year: 2021, Volume and Issue: 128(7), P. 847 - 863

Published: April 1, 2021

Dr Irvine Page proposed the Mosaic Theory of Hypertension in 1940s advocating that hypertension is result many factors interact to raise blood pressure and cause end-organ damage. Over years, modified his paradigm, new concepts regarding oxidative stress, inflammation, genetics, sodium homeostasis, microbiome have arisen allow further refinements Theory. A constant feature this approach understanding various nodes are interdependent these almost certainly vary between experimental models individuals with hypertension. This review discusses provides an introduction other reviews compendium Circulation Research .

Language: Английский

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Health benefits of resistant starch: A review of the literature

Journal of Functional Foods, Journal Year: 2022, Volume and Issue: 93, P. 105094 - 105094

Published: May 2, 2022

Starch is an essential source of energy for the human diet. Resistant starch portion that not digested in small intestine and fermented colon by microorganisms, resulting formation short-chain fatty acids, which may be associated with some metabolic effects. In this regard, review aims to present relevant research on health benefits consuming resistant its effects physiological properties such as intestinal health, glycemic balance, lipid metabolism, body weight evaluated. However, effect reducing risk diet-dependent disorders diabetes, obesity, disorders, promising but still inconclusive.

Language: Английский

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TMAO: how gut microbiota contributes to heart failure

Translational research, Journal Year: 2020, Volume and Issue: 228, P. 109 - 125

Published: Aug. 22, 2020

An increasing amount of evidence reveals that the gut microbiota is involved in pathogenesis and progression various cardiovascular diseases. In patients with heart failure (HF), splanchnic hypoperfusion causes ischemia intestinal edema, allowing bacterial translocation metabolites to enter blood circulation via an impaired barrier. This results local systemic inflammatory responses. Gut microbe-derived are implicated pathology multiple diseases, including HF. These landmark findings suggest influences host's metabolic health, either directly or indirectly by producing several metabolites. this review, we mainly discuss a newly identified microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears participate pathologic processes HF can serve as early warning marker identify individuals who at risk disease progression. We also potential gut–TMAO–HF axis new target for treatment highlight current controversies potentially exciting directions future research.

Language: Английский

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Dysbiosis of Gut Microbiota and Short‐Chain Fatty Acids in Acute Ischemic Stroke and the Subsequent Risk for Poor Functional Outcomes

Journal of Parenteral and Enteral Nutrition, Journal Year: 2020, Volume and Issue: 45(3), P. 518 - 529

Published: May 30, 2020

The intestinal microbiota and its metabolites have been reported to play an important role in stroke. Gut microbiota-originating short-chain fatty acids (SCFAs) modulate brain functions directly or indirectly through immune, endocrine, vagal, other humoral pathways. However, relatively few investigations evaluated the gut microbiome SCFAs spectrum their potential associations with stroke outcomes acute ischemic (AIS) patients different severities.We used 16S rRNA gene sequencing gas chromatography compare fecal microbial composition SCFA between AIS (n = 140) healthy controls 92). Their 90-day poor functional were by logistic regression models.We found that distinguished from controls. A lack of SCFAs-producing bacteria a low level defined dysbiosis patients, especially those increased severity. levels negatively correlated severity prognosis. Reduced levels, acetate, associated risk even after adjustments.Dysbiosis subsequent for outcomes, indicating could be prognostic markers therapeutic targets

Language: Английский

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