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Comparative characterization of the infant gut microbiome and their maternal lineage by a multi-omics approach
Here, the authors employ multi-omics on a cohort comprising three generations of family members, showing that fecal microbiota populations, functions, and metabolome of infants vary greatly from their maternal lineage, exhibiting a less diverse microbiota and differences in various metabolite classes including short- and branched-chain fatty acids.
- Tomás Clive Barker-Tejeda
- , Elisa Zubeldia-Varela
- & Alma Villaseñor
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| Open Access
Legume rhizodeposition promotes nitrogen fixation by soil microbiota under crop diversification
Sustainability in agriculture can be improved harnessing biological N2 fixation in legumes. Here, the authors combine different crops with peanut plants finding that maize and oilseed rape are the most successful combinations which have potential to enhance rhizosphere microbiota N2 fixation.
- Mengjie Qiao
- , Ruibo Sun
- & Yan Chen
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| Open Access
Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation
Growth factors rapidly raise cellular glycolysis. Here, authors unveil a mechanism where RTK/GLUT1-containing endocytic vesicles deliver glucose to glycolytic enzymes near mitochondria without upregulating cell surface glucose transporters.
- Ryouhei Tsutsumi
- , Beatrix Ueberheide
- & Yoshiro Saito
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Myeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies
Myeloid derived suppressor cells (MDSC) are associated with tumourigenesis and therapy response. Here, the authors show that beta 2-adrenergic receptor activation in MDSC leads to metabolic rewiring which regulates chemotherapy response in preclinical models of blood cancer.
- Saeed Daneshmandi
- , Jee Eun Choi
- & Hemn Mohammadpour
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| Open Access
Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles
The naked mole-rat exhibits extreme longevity, resistance to hypoxia and absence of cardiovascular disease. Here, Faulkes et al. identify mechanisms behind these traits by comparing cardiac metabolomes and transcriptomes of naked more-rats to other African mole-rat genera and evolutionary divergent mammals.
- Chris G. Faulkes
- , Thomas R. Eykyn
- & Dunja Aksentijevic
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| Open Access
Predicting and improving complex beer flavor through machine learning
Perception and appreciation of food flavour depends on many factors, posing a challenge for effective prediction. Here, the authors combine extensive chemical and sensory analyses of 250 commercial Belgian beers to train machine learning models that enable flavour and consumer appreciation prediction.
- Michiel Schreurs
- , Supinya Piampongsant
- & Kevin J. Verstrepen
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| Open Access
NMR and MS reveal characteristic metabolome atlas and optimize esophageal squamous cell carcinoma early detection
Metabolic changes often occur during the early stages of cancer development. Here, the authors develop metabolomics signatures from tissues, pre- and post-operative sera and urines in esophageal squamous cell carcinoma, which may aid in early diagnosis.
- Yan Zhao
- , Changchun Ma
- & Yan Lin
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| Open Access
PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness
Glucose metabolism is crucial for cellular energy regulation and affects the immune response. Here the authors show that nutritional supplementation of mannose may be beneficial during virus infections by rewiring glucose metabolic dysregulation and alleviating inflammatory tissue damage.
- Ronghui Liang
- , Zi-Wei Ye
- & Shuofeng Yuan
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Article
| Open Access
Metabolomic profiles of sleep-disordered breathing are associated with hypertension and diabetes mellitus development
Sleep-disordered breathing (SDB) is a prevalent disorder linked to higher cardiovascular disease risk. Here, the authors show that summary scores reflecting SDB metabolite signatures are associated with increased risks for incident hypertension and diabetes, potentially useful in guiding risk stratification.
- Ying Zhang
- , Bing Yu
- & Tamar Sofer
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| Open Access
Imputation of plasma lipid species to facilitate integration of lipidomic datasets
Advancements in plasma lipidomic profiling increase specificity of measurements but pose challenges in aligning datasets created at different times or platforms. Here the authors present a predictive framework for harmonising such datasets with different levels of granularity in their lipid measurements.
- Aleksandar Dakic
- , Jingqin Wu
- & Peter J. Meikle
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Article
| Open Access
Genetic influences on circulating retinol and its relationship to human health
Retinol, a form of vitamin A, plays an essential role in many biological processes throughout the human lifespan. Here the authors identify genetic variants that influence the level of circulating retinol and use this information to better understand how retinol impacts human health.
- William R. Reay
- , Dylan J. Kiltschewskij
- & Murray J. Cairns
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| Open Access
Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans
Fatty acid desaturation is central to metazoan lipid metabolism. Here, using C. elegans as a model, the authors show that both endogenous and microbiota-dependent small molecule signals converge to promote lipid desaturation via the nuclear receptor NHR-49/PPARα.
- Bennett W. Fox
- , Maximilian J. Helf
- & Frank C. Schroeder
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| Open Access
The impact of reproductive factors on the metabolic profile of females from menarche to menopause
Here, the authors explore the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits in over 65,000 UK Biobank to explore whether reproductive factors are likely to impact females’ metabolic profile later in life.
- Gemma L. Clayton
- , Maria Carolina Borges
- & Deborah A. Lawlor
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Short-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention
Here, the authors show that periodic restricted feeding (PRF) in Rhesus monkeys induces lasting weight loss not directly tied to reduced calories, while altering sex-specific metabolome and microbiome composition, in turn associated with long-term benefits.
- Hagai Yanai
- , Bongsoo Park
- & Isabel Beerman
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Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis
Whether Kupffer cells play a role in regulating the pathogenesis of fatty liver disease remains to be completely explored. Here, the authors show GPR3 activation stimulates glycolysis in Kupffer cells through GPR3-β-arrestin2-GAPDHPKM2 pathway and inhibits high-fat diet induced obesity and liver pathogenesis.
- Ting Dong
- , Guangan Hu
- & Jianzhu Chen
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| Open Access
Life-history stage determines the diet of ectoparasitic mites on their honey bee hosts
Varroa and Tropilaelaps mites threaten honeybee health. This study finds that mites alter feeding habits depends on their own, and hosts’, life history stage. Mites feed on the host hemolymph when parasitizing pupae during their reproductive stage but consume fat body during their dispersal stage.
- Bin Han
- , Jiangli Wu
- & Shufa Xu
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| Open Access
Muscle abnormalities worsen after post-exertional malaise in long COVID
In this longitudinal, case-controlled, cohort design study, authors show that post-exertional malaise is associated with severe exercise-induced myopathy, local and systemic metabolic disturbances and infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID.
- Brent Appelman
- , Braeden T. Charlton
- & Rob C. I. Wüst
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| Open Access
Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics
Interpreting untargeted mass spectrometry (MS) data is challenging due to incomplete reference libraries. Here, the authors created the nearest neighbor suspect spectral library from largescale public MS data, significantly enhancing the ability to hypothesize structures for unknown mass spectra.
- Wout Bittremieux
- , Nicole E. Avalon
- & Pieter C. Dorrestein
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| Open Access
Amino acid catabolite markers for early prognostication of pneumonia in patients with COVID-19
Here the authors show that elevated serum levels of deaminated amino acid catabolites involved in de novo nucleotide synthesis pathway correlate with later COVID-19 severity. These elevated levels are likely associated with abnormal proliferation of airway and vascular cells in the lung.
- Rae Maeda
- , Natsumi Seki
- & Yuki Sugiura
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Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma
Nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme for NAD synthesis, has been proposed as a potential target for cancer therapy. Here, the authors show synthetic lethality when combining NAMPT inhibition with Niacin restriction in neuroendocrine-type cancer.
- Miyuki Nomura
- , Mai Ohuchi
- & Nobuhiro Tanuma
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| Open Access
Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology
The authors developed a framework for joint protein-metabolite profiling at the single-cell level in human tissue combining targeted multiplexed protein imaging and untargeted spatial metabolomics in a single pipeline.
- Thomas Hu
- , Mayar Allam
- & Ahmet F. Coskun
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| Open Access
UniKP: a unified framework for the prediction of enzyme kinetic parameters
Prediction of enzyme kinetic parameters is essential for designing and optimising enzymes for various biotechnological and industrial applications. Here, authors presented a prediction framework (UniKP), which improves the accuracy of predictions for three enzyme kinetic parameters.
- Han Yu
- , Huaxiang Deng
- & Xiaozhou Luo
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| Open Access
The oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO2 in the yeast Komagataella phaffii
One carbon compounds such as CO2, methanol and formate are cost-effective and environmentally friendly microbial feedstocks for biomanufacturing. Here, the authors report the oxygen tolerant reductive glycine pathway in Komagataella phaffii can co-assimilate CO2, methanol and formate.
- Bernd M. Mitic
- , Christina Troyer
- & Diethard Mattanovich
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| Open Access
Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a
Here, the authors show that the gut commensal Parabacteroides distasonis alleviates insulin resistance via nicotinic acid-intestinal GPR109a axis activation, a process promoted by Dendrobium officinale polysaccharide.
- Yonggan Sun
- , Qixing Nie
- & Shaoping Nie
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| Open Access
A carbon-nitrogen negative feedback loop underlies the repeated evolution of cnidarian–Symbiodiniaceae symbioses
This study found that cnidarian animals including corals, anemones and jellyfish share a common mechanism to regulate their association with symbiotic algae. Despite evolving independently, these animals all use the same carbon-nitrogen negative feedback loop for algae control, shedding light on the repeated evolution of these marine symbiotic relationships.
- Guoxin Cui
- , Jianing Mi
- & Manuel Aranda
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Article
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Hepatocyte FBXW7-dependent activity of nutrient-sensing nuclear receptors controls systemic energy homeostasis and NASH progression in male mice
NASH, nonalcoholic steatohepatitis, a severe fatty liver disease with no cure, can manifest through loss-of-function of the E3 ligase FBXW7. Here, the authors show an underpinning of dysregulated ERRα and PPARα nuclear receptor activity, thus highlighting potential new avenues for antiNASH therapy.
- Hui Xia
- , Catherine R. Dufour
- & Vincent Giguère
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| Open Access
Coral endosymbiont growth is enhanced by metabolic interactions with bacteria
A new study reveals that bacterial partners supply essential metabolites to the vital microalgal symbionts of corals, including metabolites that boost symbiont growth. This breakthrough increases our understanding of coral microbial ecology and also opens the door to innovative ways of protecting coral reefs.
- Jennifer L. Matthews
- , Abeeha Khalil
- & Jean-Baptiste Raina
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Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring
Maternal thyroid hormone is important for fetal development. Here, the authors show that hyperthyroidism during pregnancy can program the offsprings’ glucose sensitivity and response to cold via activation of maternal thyroid hormone receptor β in a sex dependent manner
- Rebecca Oelkrug
- , Lisbeth Harder
- & Jens Mittag
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| Open Access
Endogenous renal adiponectin drives gluconeogenesis through enhancing pyruvate and fatty acid utilization
Adiponectin is a widely studied secretory protein produced by adipocytes. Here, the authors show that adiponectin is also expressed in the kidney where it is a major driver of fatty acid oxidation, from which the kidney derives energy for gluconeogenesis.
- Toshiharu Onodera
- , May-Yun Wang
- & Philipp E. Scherer
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| Open Access
Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia
Cancer cachexia is a multifactorial metabolic syndrome affecting a large fraction of patients with advanced cancer. Here the authors report a decrease in B vitamin-related liver enzymes in mouse models and gastric cancer patients with cachexia.
- Yasushi Kojima
- , Emi Mishiro-Sato
- & Masahiro Aoki
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| Open Access
Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals
The metabolic alterations underpinning aging processes and mortality in humans are not well understood. Here, the authors show that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality and longevity.
- Fenglei Wang
- , Anne-Julie Tessier
- & Marta Guasch-Ferré
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Article
| Open Access
Cold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice
During cold exposure, activated brown adipose tissue takes up a large amount of circulating glucose to fuel thermogenesis. Here, the authors show that cold stress enhances the packaging of miR-378a-3p into BAT-derived EVs, which are delivered to the liver and consequently stimulates gluconeogenesis.
- Jinhong Xu
- , Le Cui
- & Xiaohong Jiang
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Article
| Open Access
MAVS integrates glucose metabolism and RIG-I-like receptor signaling
MAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling. Here, the authors show how MAVS link RLR-mediated signaling and glucose metabolism, employing distinct mechanisms in different organelles.
- Qiao-qiao He
- , Yu Huang
- & Shi Liu
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Article
| Open Access
Portosystemic shunt placement reveals blood signatures for the development of hepatic encephalopathy through mass spectrometry
Patients with liver disease undergoing transjugular intrahepatic portosystemic shunt (TIPS) are at a higher risk of hepatic encephalopathy (HE). Here, the authors show intrahepatic shunting and specific metabolites, especially bile acids, as potential biomarkers and treatment targets for HE.
- Ana Carolina Dantas Machado
- , Stephany Flores Ramos
- & Amir Zarrinpar
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| Open Access
CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications
Osteoarthritis is a prevalent age-related disease. Here, the authors show that that CircRREB1 is highly expressed in second generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression.
- Zhe Gong
- , Jinjin Zhu
- & Shuying Shen
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Article
| Open Access
Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging
Single-cell analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, the authors utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging to enable high-throughput in situ profiling of single-cell lipidome.
- Hua Zhang
- , Yuan Liu
- & Lingjun Li
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| Open Access
Simultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics
Untargeted metabolomics enables simultaneous measurement of xenobiotic fate and effects in biological systems. This is demonstrated through discovering extensive biotransformation maps, measuring systemic exposures over time, and directly associating endogenous biochemical responses to internal dose.
- Tara J. Bowen
- , Andrew D. Southam
- & Mark R. Viant
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| Open Access
A BAHD-type acyltransferase concludes the biosynthetic pathway of non-bitter glycoalkaloids in ripe tomato fruit
During tomato fruit ripening, bitter and toxic steroidal glycoalkaloids (SGAs) are converted to nonbitter and less toxic forms, but proposed acylating enzyme in pathway remain unknown. Here, authors report BAHD-type acyltransferase that catalyze acylation step in biosynthesis of non-bitter SGAs in tomato.
- Prashant D. Sonawane
- , Sachin A. Gharat
- & Asaph Aharoni
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Article
| Open Access
Salicylic acid metabolism and signalling coordinate senescence initiation in aspen in nature
Deciduous trees exhibit autumn senescence driven by environmental seasonality. Here, the authors show that senescence timing in aspen tree genotypes depends on environmental changes but also on the ability of each genotype to sustain stress tolerance mediated by the phytohormone salicylic acid.
- Jenna Lihavainen
- , Jan Šimura
- & Stefan Jansson
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| Open Access
Deep-profiling of phospholipidome via rapid orthogonal separations and isomer-resolved mass spectrometry
The existence of large number of isomers poses challenges for lipidomic analysis. The authors integrate hydrophilic interaction liquid chromatography, trapped ion mobility, and isomer-resolved MS/MS into a single system, enabling deep profiling of phospholipidomes at fast speed and wide coverage.
- Tian Xia
- , Feng Zhou
- & Yu Xia
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Article
| Open Access
Mass spectrometry imaging for biosolids characterization to assess ecological or health risks before reuse
Mass spectrometry imaging is a suitable tool for the analysis of non-cohesive materials. Here, authors show that it can be used to detect persistent organic pollutants (POPs) and heavy metals (HMs) in biosolids using small amounts of material with speed and safety.
- Claire Villette
- , Loïc Maurer
- & Dimitri Heintz
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Article
| Open Access
Trackable and scalable LC-MS metabolomics data processing using asari
Reproducible and scalable data processing is key to the progress of metabolomics. Here, the authors present a software tool that offers predictable metabolomics feature detection and improved computational performance in large datasets.
- Shuzhao Li
- , Amnah Siddiqa
- & Shujian Zheng
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Article
| Open Access
Empowering drug off-target discovery with metabolic and structural analysis
The authors present a workflow integrating metabolic perturbations with protein structural analysis to identify drug off-targets, demonstrating how combining machine learning methods with mechanistic analyses can benefit off-target identification.
- Sourav Chowdhury
- , Daniel C. Zielinski
- & Eugene I. Shakhnovich
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Article
| Open Access
Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations
Here, the authors perform a whole-genome sequencing association analysis of genetic variants in ≤11,840 multi-ethnic participants with ≤1666 circulating metabolites, discovering 1985 novel variant-metabolite associations and insights into human disease.
- Elena V. Feofanova
- , Michael R. Brown
- & Bing Yu
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Article
| Open Access
Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem
Isotopologue spectral analysis was originally designed to assess metabolic fluxes from bulk samples. Here, the authors adapted this approach to infer fluxes from discrete regions in tissue by using mass spectrometry imaging, showing increased fatty acid synthesis flux in brain tumors of mice.
- Michaela Schwaiger-Haber
- , Ethan Stancliffe
- & Gary J. Patti
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Article
| Open Access
Spatially resolved multi-omics highlights cell-specific metabolic remodeling and interactions in gastric cancer
The spatial signature of metabolic remodeling in tumours remains to be explored. Here, the integration of mass spectrometry imaging-based spatial metabolomics and lipidomics with microarray-based spatial transcriptomics allows the visualisation of metabolic heterogeneity in gastric cancer.
- Chenglong Sun
- , Anqiang Wang
- & Jiuming He
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Article
| Open Access
Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation
Severe COVID-19 is characterized by an accumulation of and functional changes in neutrophils. Using metabolomics, the authors demonstrate that neutrophils display a reduction in GAPDH activity in severe COVID-19 and that GAPDH inhibition promotes neutrophil extracellular trap formation.
- Yafeng Li
- , Jessica S. Hook
- & Michalis Agathocleous
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Article
| Open Access
Methionine restriction constrains lipoylation and activates mitochondria for nitrogenic synthesis of amino acids
Methionine restriction (MR) provides metabolic benefits in many organisms. Here, the authors report that MR is sensed by yeast mitochondria as a sign of SAM deprivation; in response, the mitochondria redirect carbon metabolism to fuel nitrogen anabolism in a lipoate-dependent mechanism.
- Wen Fang
- , Liu Jiang
- & Cunqi Ye
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Article
| Open Access
PeakDecoder enables machine learning-based metabolite annotation and accurate profiling in multidimensional mass spectrometry measurements
Alternative algorithms exploiting advantages of multidimensional mass spectrometry in untargeted metabolomics are needed. Here, the authors develop and demonstrate PeakDecoder for confident and accurate metabolite profiling in 116 microbial sample runs and using a library built from 64 standards.
- Aivett Bilbao
- , Nathalie Munoz
- & Kristin E. Burnum-Johnson
Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks