ArticleProceedings of the National Academy of Sciences of the United States of America2015
Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 191 citations in OpenAlex.
- A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules.Cell host & microbe · 2025Pooled it
- Bacterial cell envelope components of gut commensals: effects in host-microbe interaction.Annals of medicine · 2026Review
- Bacterial lipid structural diversity mediates commensalism and pathogenesis.Nature reviews. Microbiology · 2026Review
- Non-redundant cardiolipin synthase family proteins shape lipid composition and stress resilience inbioRxiv : the preprint server for biology · 2026Article
- Article
- Endocannabinoids and related lipids in host metabolism-gut microbiome signalling.Nature reviews. Endocrinology · 2026Review
- Comparative Metabolomics Reveals the Production of Sulfated Metabolites by Human Gut Bacteria.Journal of the American Chemical Society · 2026Article
- Transcriptomics-based analysis to explore the effects of culture media and cell models on the function of B. pseudocatenulatum strains of intestinal origin.BMC genomics · 2026Article
- The human microbiome as a source of novel bioactive natural products: structures, bioactivities, and biosynthetic insights.Journal of natural medicines · 2026Review
- The microbiome regulates host metabolic health and diseases through microbial enzymes.Nature reviews. Gastroenterology & hepatology · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- Mass spectrometry-based metabolomics approaches to interrogate host-microbiome interactions in mammalian systems.Natural product reports · 2026Review
- Bacteroides-derived endocannabinoid-like commendamide attenuates skeletal muscle ferroptosis in vitro: implications for Duchenne muscular dystrophy.Journal of translational medicine · 2026Article
- Ornithine lipids and other acyloxyacyl amino lipids: the coming-of-age story of a group of non-canonical membrane lipids.Applied microbiology and biotechnology · 2026Review
- Dual immunomodulatory effects ofFrontiers in microbiology · 2026Article
- Article
- Fiber-Dependent Microbiome Glycine Lipids Ameliorate Steatotic Liver Disease in Mice via Mitochondrial Enhancement.Gastro hep advances · 2026Article
- Tetracycline Antibiotics Induce Biosynthesis of Pro-Inflammatory Metabolites in the ImmunobioticACS central science · 2025Article
- The role of metaorganismal lipid metabolism in human health and disease.Immunometabolism (Cobham, Surrey) · 2025Article
- Development of a Transcriptional Biosensor for Hydrogen Sulfide That Functions under Aerobic and Anaerobic Conditions.ACS synthetic biology · 2025Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The trillions of bacteria that make up the human microbiome are believed to encode functions that are important to human health; however, little is known about the specific effectors that commensal bacteria use to interact with the human host. Functional metagenomics provides a systematic means of surveying commensal DNA for genes that encode effector functions. Here, we examine 3,000 Mb of metagenomic DNA cloned from three phenotypically distinct patients for effectors that activate NF-κB, a transcription factor known to play a central role in mediating responses to environmental stimuli. This screen led to the identification of 26 unique commensal bacteria effector genes (Cbegs) that are predicted to encode proteins with diverse catabolic, anabolic, and ligand-binding functions and most frequently interact with either glycans or lipids. Detailed analysis of one effector gene family (Cbeg12) recovered from all three patient libraries found that it encodes for the production of N-acyl-3-hydroxypalmitoyl-glycine (commendamide). This metabolite was also found in culture broth from the commensal bacterium Bacteroides vulgatus, which harbors a gene highly similar to Cbeg12. Commendamide resembles long-chain N-acyl-amides that function as mammalian signaling molecules through activation of G-protein-coupled receptors (GPCRs), which led us to the observation that commendamide activates the GPCR G2A/GPR132. G2A has been implicated in disease models of autoimmunity and atherosclerosis. This study shows the utility of functional metagenomics for identifying potential mechanisms used by commensal bacteria for host interactions and outlines a functional metagenomics-based pipeline for the systematic identification of diverse commensal bacteria effectors that impact host cellular functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.