The fecal metabolome as a functional readout of the gut microbiome

The human gut microbiome plays a key role in human health1, but 16S characterization lacks quantitative functional annotation2. The fecal metabolome provides a functional readout of microbial activity and can be used as an intermediate phenotype mediating host–microbiome interactions3. In this comprehensive description of the fecal metabolome, examining 1,116 metabolites from 786 individuals from a population-based twin study (TwinsUK), the fecal metabolome was found to be only modestly influenced by host genetics (heritability (H2) = 17.9%). One replicated locus at the NAT2 gene was associated with fecal metabolic traits. The fecal metabolome largely reflects gut microbial composition, explaining on average 67.7% (±18.8%) of its variance. It is strongly associated with visceral-fat mass, thereby illustrating potential mechanisms underlying the well-established microbial influence on abdominal obesity. Fecal metabolic profiling thus is a novel tool to explore links among microbiome composition, host phenotypes, and heritable complex traits. Comprehensive fecal metabolic profiling in 786 individuals from TwinsUK provides insights into the influence of host genetics and gut microbial composition on metabolites that may mediate microbiome-associated phenotypes.

• Publication year

  2018

• Venue

  Nature Genetics

• Publication date

  2018-05-28

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1038/s41588-018-0135-7PMID 29808030PMCID 6104805
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Whole-genome sequencing identifies common-to-rare variants associated with human blood metabolites

  2017cited by this paper
• Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

  2017cited by this paper
• Genetic effects on gene expression across human tissues

  2017cited by this paper
• Ensembl 2018

  2017cited by this paper
• Microbiota-induced obesity requires farnesoid X receptor

  2016cited by this paper
• The gut microbiota and metabolic disease: current understanding and future perspectives

  2016cited by this paper
• Human gut microbes impact host serum metabolome and insulin sensitivity

  2016cited by this paper
• MG-RAST, a Metagenomics Service for Analysis of Microbial Community Structure and Function.

  2016cited by this paper
• Heritable components of the human fecal microbiome are associated with visceral fat

  2016cited by this paper
• Deep sequencing of 10,000 human genomes

  2016cited by this paper
• Genetic Determinants of the Gut Microbiome in UK Twins.

  2016cited by this paper
• Metabolomic profiling to dissect the role of visceral fat in cardiometabolic health

  2016cited by this paper
• Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome.

  2015cited by this paper
• Gut microbiota composition associated with stool consistency

  2015cited by this paper
• Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates

  2015cited by this paper
• Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality

  2015cited by this paper
• De novo clustering methods outperform reference-based methods for assigning 16S rRNA gene sequences to operational taxonomic units

  2015cited by this paper
• Dead or Alive: Molecular Assessment of Microbial Viability

  2014cited by this paper
• PharmGKB summary: uric acid-lowering drugs pathway, pharmacodynamics

  2014cited by this paper
• Human genetics shape the gut microbiome.

  2014cited by this paper
• Fitting Linear Mixed-Effects Models Using lme4

  2014cited by this paper
• High Resolution Mass Spectrometry Improves Data Quantity and Quality as Compared to Unit Mass Resolution Mass Spectrometry in High- Throughput Profiling Metabolomics

  2014cited by this paper
• An atlas of genetic influences on human blood metabolites

  2014cited by this paper
• PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2.

  2014cited by this paper
• Minireview: Gut microbiota: the neglected endocrine organ.

  2014cited by this paper
• Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods

  2013cited by this paper
• COHORT PROFILE Cohort Profile : TwinsUK and Healthy Ageing Twin Study

  2013cited by this paper
• A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice

  2013cited by this paper
• Guidelines for estimating repeatability

  2012cited by this paper
• Dual-Energy X-Ray Absorptiometry for Quantification of Visceral Fat

  2012cited by this paper
• Genome-wide Efficient Mixed Model Analysis for Association Studies

  2012cited by this paper
• Human gut microbiome viewed across age and geography

  2012cited by this paper
• On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies

  2012cited by this paper
• Improved heritability estimation from genome-wide SNPs.

  2012cited by this paper
• GCTA: a tool for genome-wide complex trait analysis.

  2011cited by this paper
• UCHIME improves sensitivity and speed of chimera detection

  2011cited by this paper
• MICE: Multivariate Imputation by Chained Equations in R

  2011cited by this paper
• Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample

  2010cited by this paper
• Gut microbiota: Changes throughout the lifespan from infancy to elderly

  2010cited by this paper
• Organization of GC/MS and LC/MS metabolomics data into chemical libraries

  2010cited by this paper
• Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems.

  2009cited by this paper
• Impact of Gut Microbiota on Intestinal and Hepatic Levels of Phase 2 Xenobiotic-Metabolizing Enzymes in the Rat

  2009cited by this paper
• A core gut microbiome in obese and lean twins

  2008cited by this paper
• Accuracy of body mass index in diagnosing obesity in the adult general population

  2008cited by this paper
• Microbial community gene expression in ocean surface waters

  2008cited by this paper
• gap: Genetic Analysis Package

  2007cited by this paper
• Microbial ecology: Human gut microbes associated with obesity

  2006cited by this paper
• The gut flora as a forgotten organ

  2006cited by this paper
• UniFrac: a New Phylogenetic Method for Comparing Microbial Communities

  2005cited by this paper
• Measurement of caffeine and five of the major metabolites in urine by high-performance liquid chromatography/tandem mass spectrometry.

  2005cited by this paper
• NAT2 and CYP1A2 phenotyping with caffeine: head-to-head comparison of AFMU vs. AAMU in the urine metabolite ratios.

  2003cited by this paper
• Methodology for Genetic Studies of Twins and Families

  1992cited by this paper
• Graph drawing by force‐directed placement

  1991cited by this paper
• Distributed under Creative Commons Cc-by 4.0 a Heritability-based Comparison of Methods Used to Cluster 16s Rrna Gene Sequences into Operational Taxonomic Units

  year unknowncited by this paper

• Metabolomic Markers of Left Ventricular Structure, Diastolic Function, and Risk of Coronary Heart Disease: A Longitudinal Study in American Indian Individuals.

  2026cites this paper
• Genome-wide association analyses highlight the role of the intestinal molecular environment in human gut microbiota variation.

  2026cites this paper
• Stool Metabolomics Reveals Catecholamine and Tryptophan-NAD+ Pathway Alterations in Autism Spectrum Disorder

  2026cites this paper
• Structured Exercise Modulates Gut Microbiota Composition and Protects Against Diet-Induced Dysbiosis in a Rat Model

  2026cites this paper
• Lactobacillus plantarum TY-S8 ameliorates hyperuricemia through the regulation of gut microbiota and tryptophan metabolism in mice.

  2026cites this paper
• Changes in the microbiome and metabolome in captive red kangaroos (Osphranter rufus) affected by macropod progressive periodontal disease.

  2026cites this paper
• Prospects for Using Multi-omics to Advance the Bioremediation of Organic Micropollutants in Aquatic Environments: A Review

  2026cites this paper
• Gut Health and Athletic Performance: Investigating the Influence of Nutrition on Microbiome Composition and Function

  2026cites this paper
• Advancing fecal volatilome profiling by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry and image pattern recognition.

  2026cites this paper
• Gut microbiota and metabolite disruption during breast cancer chemotherapy is associated with peripheral neuropathy sensory symptoms and pain.

  2026cites this paper
• Gut ecosystem dysfunction in parkinson's disease: deciphering faecal metabolome-metagenome links for novel diagnostic panels.

  2026cites this paper
• Modeling diet-gut microbiome interactions and prebiotic responses in Thai adults.

  2026cites this paper
• Decoding the Therapeutic Target SVEP1: Harnessing Molecular Trait GWASs to Unravel Mechanisms of Human Disease.

  2025cites this paper
• Distribution of gut microbiota across intestinal segments and their impact on human physiological and pathological processes

  2025cites this paper
• All roads lead to Rome: the plasticity of gut microbiome drives the extensive adaptation of the Yarkand toad-headed agama (Phrynocephalus axillaris) to different altitudes

  2025cites this paper
• Branched perfluorohexanesulfonic acid (PFHxS) and perfluoroheptanoic acid (PFHpA): 'Safer' per- and polyfluoroalkyl substances (PFASs) alternatives for their effects on gut microbiota and metabolic function in children.

  2025cites this paper
• Vitamin biosynthesis in the gut: interplay between mammalian host and its resident microbiota

  2025cites this paper
• Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma

  2025cites this paper
• Universal, untargeted detection of bacteria in tissues using metabolomics workflows

  2025cites this paper
• Integrated multi-omic and symptom clustering reveals lower-gastrointestinal disorders of gut-brain interaction heterogeneity

  2025cites this paper
• Microbiota intestinal y eje intestino-cerebro: una revisión de su interacción con el sistema nervioso central

  2025cites this paper
• Dried blood spots capture a wide range of metabolic pathways and biological changes associated with exercise

  2025cites this paper
• Metabolomic profiles in allergic rhinitis: a systematic review and meta-analysis.

  2025cites this paper
• Microbiota–Gut–Brain Axis: Mass-Spectrometry-Based Metabolomics in the Study of Microbiome Mediators—Stress Relationship

  2025cites this paper
• Deciphering the coordinated roles of the host genome, duodenal mucosal genes, and microbiota in regulating complex traits in chickens

  2025cites this paper
• Gut microbiome reveals the trophic variation and significant adaption of three sympatric forest-dwelling ungulates on the eastern Qinghai-Xizang Plateau

  2025cites this paper
• A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson’s Disease

  2025cites this paper
• Relationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology

  2025cites this paper
• Olsenella scatoligenes-derived skatole promotes smooth muscle cell proliferation and migration to aggravate atherosclerosis

  2025cites this paper
• Integrating Gut Microbiome and Metabolome to Gain Insight into Metabolic Dysfunction-Associated Steatotic Liver Disease

  2025cites this paper
• Microbial Metabolomes in Alzheimer’s Disease: From Pathogenesis to Therapeutic Potential

  2025cites this paper
• Resistance Training Reshapes the Gut Microbiome for Better Health

  2025cites this paper
• Comparative analysis of heavy metals, gut microbial community and metabolome between bean geese (Anser fabalis) wintering at Caizi and Shengjin lakes, China

  2025cites this paper
• Biomonitoring Xenobiotics in Human Biospecimens: Challenges, Advances, and the Future of Exposome Characterization

  2025cites this paper
• Interplay of gut microbiome and metabolome in various blood pressure phenotypes based on ambulatory BP monitoring reveal new insights in nondipper patients

  2025cites this paper
• Multi-omics analyses of the gut microbiome, fecal metabolome, and multimodal brain MRI reveal the role of Alistipes and its related metabolites in major depressive disorder

  2025cites this paper
• Integrated analysis of blood microbiome and metabolites reveals key biomarkers and functional pathways in myocardial infarction

  2025cites this paper
• Effect of Lactobacillus plantarum Extracellular Vesicles on Lipid Metabolism in Mice Fed a High‐Fat Diet

  2025cites this paper
• Lipidomics, Microbiota, and Intestinal Clostridioides difficile Infection Outcome

  2025cites this paper
• Characterization of gut microbiota and metabolites in individuals with constipation-predominant irritable bowel syndrome

  2025cites this paper
• From gut to gamete: how the microbiome influences fertility and preconception health

  2025cites this paper
• Dietary and Pharmacological Modulation of Aging-Related Metabolic Pathways: Molecular Insights, Clinical Evidence, and a Translational Model

  2025cites this paper
• Synergistic interactions between gut microbiota and its associated microbial metabolites in Hermetia illucens mediate the reduction of hexavalent chromium.

  2025cites this paper
• Faecal metabolites as a readout of habitual diet capture dietary interactions with the gut microbiome

  2025cites this paper
• Microbiota-mediated modulation of radiosensitivity: mechanisms and therapeutic prospects of oral and gut microbiota, metabolites, and probiotics

  2025cites this paper
• Standardization of Fecal Metabolomics Using Microbiome Preservation Kits: Implications for Multiomics Integration

  2025cites this paper
• Fecal metabolic variations of Apostichopus japonicus induced by dietary sea mud components in the recirculating aquaculture environment

  2025cites this paper
• Fecal Microbiome and Metabolomic Profiles of Mixed-Fed Infants Are More Similar to Formula-Fed than Breastfed Infants

  2025cites this paper
• Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum

  2025cites this paper
• Uncovering de novo polyamine biosynthesis in the gut microbiome and its alteration in inflammatory bowel disease

  2025cites this paper
• Evaluation of solutions for stabilizing feces in metabolomics studies using GC × GC-TOFMS

  2025cites this paper
• Fecal metabolomics to understand intestinal dysfunction in male dairy beef calves at arrival to the rearing farm

  2025cites this paper
• Longitudinal characterization of the metabolome of dairy cows transitioning from one lactation to the next: Investigations in fecal samples.

  2025cites this paper
• Multi-Omics Analysis Revealed the Molecular Mechanisms Affecting Average Daily Gain in Cattle

  2025cites this paper
• Microbiome-metabolome generated bile acids gatekeep infliximab efficacy in Crohn's disease by licensing M1 suppression and Treg dominance.

  2025cites this paper
• Advanced computational tools, artificial intelligence and machine-learning approaches in gut microbiota and biomarker identification

  2025cites this paper
• Revealing Spatial Heterogeneity across the Gut Tissue-Lumen Interface through MALDI Mass Spectrometry Imaging

  2025cites this paper
• Gut-associated metabolites and diabetes pathology: a systematic review

  2025cites this paper
• EFFECTS OF CLOSTRIDIUM BUTYRICUM SUPPLEMENTATION ON FECAL MICROBIOTA AND METABOLITES IN CAPTIVE RED KANGAROO (MACROPUS RUFUS)

  2025cites this paper
• Linking oxysterols and different stages of mild cognitive impairment: insights from gut metabolites and N6-methyladenosine

  2025cites this paper
• Insights into human respiratory microbiome under dysbiosis and its analysis tool

  2025cites this paper
• Multi-omics approach identifies gut microbiota variations associated with depression

  2025cites this paper
• NMR-based metabolomics: Where are we now and where are we going?

  2025cites this paper
• Unraveling the Relation of Parkinson's Disease and Metabolites: A Combined Analysis of Stool and Plasma Metabolites Based on Untargeted Metabolomics Technology

  2025cites this paper
• Variations in Intestinal Microbiota Among Three Species in the Cervidae Family Under the Same Feeding Conditions

  2025cites this paper
• Associations of fecal and blood microbiota-related metabolites with gut microbiota and type 2 diabetes in HIV infection.

  2025cites this paper
• Chemical activity profiling reveals how exposure to drugs or dietary compounds alters gut microbial biotransformation capacity

  2025cites this paper
• The role of the gut and intestinal dysbiosis in the pathogenesis of Spondyloarthritis.

  2025cites this paper
• Dendrobium nobile Lindl. Polysaccharides ameliorate the inflammatory microenvironment in the retina of diabetic rats: a multi-omics study of the gut-blood-retina axis.

  2025cites this paper
• Genetic regulation of fatty acid content in adipose tissue

  2025cites this paper
• Faecal amino acids stability: investigating optimal sampling conditions for analysis

  2025cites this paper
• Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment

  2025cites this paper
• Problems and prospects of metabolomic studies in the alteration of the gut microbiome.

  2025cites this paper
• Makgeolli Lees as a Novel Prebiotic Candidate: Effects on Human Gut Microbiota and Metabolites

  2025cites this paper
• Comparative Analysis of Fecal Microbiota and Metabolomic Profiles in Male and Female Leizhou Goats Offered a 10% Crude Protein Diet Among Four Energy Levels

  2025cites this paper
• Early life gut microbial and metabolic shifts reflected in stool consistency- a gut transit time proxy

  2025cites this paper
• Characterization of Vitreous Microbiota Dysbiosis Associated with Proliferative Diabetic Retinopathy

  2025cites this paper
• Synbiotic modulation of adult gut microbiome by 2′-fucosyllactose and Bifidobacterium longum subsp. infantis EFEL8008

  2025cites this paper
• Microbial-Purine Metabolic Crosstalk Regulates Colitis-Related Intestinal Fibrosis: A Multi-Omics and Cohort Analysis Approach.

  2025cites this paper
• Effect of fecal microbiota transplantation on gut microbiota functional profile in recipients of allogeneic hematopoietic cell transplantation

  2025cites this paper
• Emerging concepts and shifting paradigms for understanding the microbial basis of inflammatory bowel diseases

  2025cites this paper
• New insights into the molecular biology of Alzheimer’s-like cerebral amyloidosis achieved through multi‐omics approaches

  2025cites this paper
• Enteric delivery of indole-3-carboxylic acid unlocks therapeutic potential of postbiotic metabolite cascade.

  2025cites this paper
• Activated carbon ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota

  2025cites this paper
• Dynamics of gut metabolome and microbiota maturation during early life

  2025cites this paper
• Microbial lipid shifts in a multi-stage simulated gut

  2025cites this paper
• Harnessing Metabolomics to Advance Nutrition-Based Therapeutics for Inflammation: A Systematic Review of Randomized Clinical Trials

  2025cites this paper
• Microbiome based precision medicine through integrated multiomics and machine learning.

  2025cites this paper
• Gut microbial metabolites and cardiometabolic disorders: new targets for prevention and treatment.

  2025cites this paper
• Effect of Yoga and Meditation on Human Gut Microbiota: A Systematic Review

  2025cites this paper
• Phenotype-driven parallel embedding for microbiome multi-omic data integration

  2025cites this paper
• Longitudinal characterization of fecal amino acid, biogenic amines and amino acid-related metabolites in dairy heifers from birth to first calving

  2025cites this paper
• Synthetic microbial community in pristine environment promotes the growth of the endangered plant Lilium tsingtauense

  2025cites this paper
• Longitudinal characterization of fecal lipids in dairy heifers from birth to first calving.

  2025cites this paper
• Metabolomics analysis of gut metabolites in patients with colorectal polyps and in healthy individuals

  2025cites this paper
• Development of an untargeted metabolomics analytical protocol for fecal samples by liquid chromatography–mass spectrometry

  2025cites this paper
• Intestinal metabolites predict treatment resistance of patients with depression and anxiety

  2024cites this paper
• Integrated 16S rRNA sequencing and metabolomic analysis reveals the potential protective mechanism of Germacrone on diabetic nephropathy in mice

  2024cites this paper
• Lung Mycobacterium tuberculosis infection perturbs metabolic pathways in non-pulmonary tissues

  2024cites this paper
• The Role of the FODMAP Diet in IBS

  2024cites this paper