Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling
Open accessAbstract
The gastrointestinal microbiota is emerging as a unique and inexhaustible source for metabolites with potential to modulate G‐protein coupled receptors (GPCRs). The ghrelin receptor [growth hormone secretagogue receptor (GHSR)‐1a] is a GPCR expressed throughout both the gut and the brain and plays a crucial role in maintaining energy balance, metabolism, and the central modulation of food intake, motivation, reward, and mood. To date, few studies have investigated the potential of the gastrointestinal microbiota and its metabolites to modulate GPCR signaling. Here we investigate the ability of short‐chain fatty acids (SCFAs), lactate, and different bacterial strains, including Bifidobacterium and Lactobacillus genera, to modulate GHSR‐1a signaling. We identify, for what is to our knowledge the first time, a potent effect of microbiota‐derived metabolites on GHSR‐1a signaling with potential significant consequences for host metabolism and physiology. We show that SCFAs, lactate, and bacterial supernatants are able to attenuate ghrelin‐mediated signaling through the GHSR‐1a. We suggest a novel route of communication between the gut microbiota and the host via modulation of GHSR‐1a receptor signaling. Together, this highlights the emerging therapeutic potential in the exploration of the microbiota metabolome in the specific targeting of key GPCRs, with pleiotropic actions that span both the CNS and periphery.—Torres‐Fuentes, C., Golubeva, A. V., Zhdanov, A. V., Wallace, S., Arboleya, S., Papkovsky, D. B., El Aidy, S., Ross, P., Roy, B. L., Stanton, C., Dinan, T. G., Cryan, J. F., Schellekens, H. Short‐chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling. FASEB J. 33, 13546‐13559 (2019). www.fasebj.org
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- Authors
- Torres‐Fuentes, C., Golubeva, A. V., Zhdanov, A. V., Wallace, S., Arboleya, S., Papkovsky, D. B., Aidy, S. E., Ross, P., Roy, B. L., Stanton, C., Dinan, T. G., Cryan, J. F., & Schellekens, H.
- Affiliations
- University College Cork (IE)
- Teagasc - The Irish Agriculture and Food Development Authority (IE)
- School of Biochemistry and Cell Biology University College Cork Cork Ireland
- Alimentary Pharmabiotic Centre (APC) Microbiome Ireland, University College Cork Cork Ireland
- Cremo SA Fribourg Switzerland
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2019-10-09
- Volume
- 33
- Issue
- 12
- Pages
- 13546-13559
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2975275554
- Cited by
- 154
- References
- 71
- Citations by year
- 2026: 11 · 2025: 29 · 2024: 26 · 2023: 21 · 2022: 18 · 2021: 33 · 2020: 16
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Rovira & Virgili repository (submittedVersion, cc-by)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Science Foundation Ireland (SFI/12/RC/, 12/RC/2276, 12/RC/2273, 12/RC/, SFI/12/RC/2273.)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- short-chain fatty acids, gut microbiota metabolites, growth hormone secretagogue receptor, GHS-R1a, G protein-coupled receptor signaling, lactate, Bifidobacterium, Lactobacillus, gut-brain axis, appetite regulation, energy balance, bacterial supernatant
- MeSH terms
- Gastrointestinal Microbiome, Bacteria, Fatty Acids, Volatile, Gene Expression Regulation, Humans, Signal Transduction, Lactic Acid, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Ghrelin, Receptors, Ghrelin, HEK293 Cells, TOR Serine-Threonine Kinases
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