Cited by 154Gut microbiota and healthRegulation of Appetite and ObesityGastrointestinal motility and disorders

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Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling

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Torres‐Fuentes, Cristina, Golubeva, Anna V., Zhdanov, Alexander V., Wallace, Shauna, Arboleya, Silvia, Papkovsky, Dimitri B., Aidy, Sahar El, Ross, Paul, Roy, Bernard L., Stanton, Catherine, Dinan, Timothy G., Cryan, John F., Schellekens, Harriet·2019·The FASEB Journal

DOI 10.1096/fj.201901433r

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Abstract

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: Torres‐Fuentes, Cristina
Golubeva, Anna V.
Zhdanov, Alexander V.
Arboleya, Silvia
Aidy, Sahar El
Stanton, Catherine
Dinan, Timothy G.
Cryan, John F.
Venue: The FASEB Journal
Publisher: Wiley
Published: 2019-10-09
Volume: 33
Issue: 12
Pages: 13546-13559
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.201901433r
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
Licence: cc-by
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling

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