ArticleNature communications2024
Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Article
- The Gut-Heart-Kidney Axis in Heart Failure: Trimethylamine N-Oxide and Beyond-A State-of-the-Art Review.Biomedicines · 2026Review
- Phenylacetic Acid, a Gut Microbially Produced Metabolite, Reduces Atherosclerosis Burden and Impacts Host Lipid Homeostasis.Journal of the American Heart Association · 2026Article
- Integrated analysis of gut microbiota, serum metabolomics, and proteomics reveals novel associations with clinical symptoms in patients with cerebral infarction.BMC microbiology · 2026Article
- Effect of the gut microbiota metabolite phenylacetylglycine on cardiac CaBiophysical reports · 2026Article
- Unraveling the nexus in the neuro-neoplastic progression of colorectal cancer: Potential role of β2-adrenergic receptor (β2-AR).Journal of advanced research · 2026Review
- Microbiota-derived metabolites and cardiovascular implications in Inflammatory Bowel Disease (IBD).Molecular medicine (Cambridge, Mass.) · 2026Review
- Gut microbe-derivedProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Regulation of allergies across the body by microbial metabolites.Experimental & molecular medicine · 2026Review
- Microbial Metabolite 4EPS Inhibits AT1R to Reduce Blood Pressure and Aortic Aneurysm Outcome.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Gut-Heart Axis in Myocardial Repair: Mechanisms, Cross-Organ Networks, and Therapeutic Opportunities.Circulation research · 2026Review
- Dietary Nutrients, Gut Microbiota, and Cardiac Function: From Metabolic Mechanisms to Clinical Applications.Nutrients · 2026Review
- G Protein-Coupled Receptors in Irritable Bowel Syndrome: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Mixed short-chain fatty acids and high-fiber diet reshape SCFA profiles and attenuate post-infarction cardiac fibrosis in mice.Frontiers in cardiovascular medicine · 2026Article
- The gut microbiota-aromatic amino acid axis in cardiovascular disease: pathophysiological roles, translational biomarkers, and therapeutic targeting.Frontiers in cardiovascular medicine · 2026Review
- Comorbidity Between Mood Disorders and Chronic Somatic Diseases, With a Focus on Cardiometabolic Disease, and Its Mechanistic Crosstalk.Depression and anxiety · 2026Review
- The gut microbiome-cardiometabolic axis: insights into obesity, type 2 diabetes, and hypertension.Frontiers in endocrinology · 2026Review
- Gut Microbiota and Atherosclerosis: Integrative Multi-Omics and Mechanistic Insights.Current atherosclerosis reports · 2025Review
- Associations of Plasma Metabolite Phenylacetylglutamine on Coronary Plaque Characterization in Patients with ST-Segment Elevation Myocardial Infarction.Cardiovascular toxicology · 2025Article
- The slow delayed rectifier KScientific reports · 2025Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Allosteric modulation is a central mechanism for metabolic regulation but has yet to be described for a gut microbiota-host interaction. Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, has previously been clinically associated with and mechanistically linked to cardiovascular disease (CVD) and heart failure (HF). Here, using cells expressing β1- versus β2-adrenergic receptors (β1AR and β2AR), PAGln is shown to act as a negative allosteric modulator (NAM) of β2AR, but not β1AR. In functional studies, PAGln is further shown to promote NAM effects in both isolated male mouse cardiomyocytes and failing human heart left ventricle muscle (contracting trabeculae). Finally, using in silico docking studies coupled with site-directed mutagenesis and functional analyses, we identified sites on β2AR (residues E122 and V206) that when mutated still confer responsiveness to canonical β2AR agonists but no longer show PAGln-elicited NAM activity. The present studies reveal the gut microbiota-obligate metabolite PAGln as an endogenous NAM of a host GPCR.
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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 Socratic graph.