ArticleScientific reports2020
The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- DuodenalGut · 2022Trial
- Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes.BMC microbiology · 2022Trial
- Gut microbiota metabolic reprogramming drives the development of metabolic diseases in the host.Gut microbes · 2026Review
- Glucagon-like peptide-1: a critical link between gut microbiota dysbiosis and degenerative musculoskeletal diseases.Gut microbes · 2026Review
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- GLP-1 agonists and the gut microbiome: A bidirectional relationship.British journal of clinical pharmacology · 2026Review
- GLP-1 Receptor Agonists at the Crossroads of Circadian Biology, Sleep, and Metabolic Disease.International journal of molecular sciences · 2026Review
- Gut microbiota and metabolic disease risk in youth.Cell reports. Medicine · 2026Review
- Unveiling Butyrate as a Parkinson's Disease Therapy.Neuroscience bulletin · 2026Review
- Intermittent Fasting and Probiotics for Gut Microbiota Modulation in Type 2 Diabetes Mellitus: A Narrative Review.Nutrients · 2025Review
- Biological functions and pharmacological behaviors of bile acids in metabolic diseases.Journal of advanced research · 2025Review
- The Gut-Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications.Movement disorders clinical practice · 2025Review
- Bidirectional Interactions Between the Gut Microbiota and Incretin-Based Therapies.Life (Basel, Switzerland) · 2025Review
- The gut-brain axis in early Parkinson's disease: from prodrome to prevention.Journal of neurology · 2025Review
- Gut Microbiome Regulation of Gut Hormone Secretion.Endocrinology · 2025Review
- Review
- Article
- Mechanism of action of the bile acid receptor TGR5 in obesity.Acta pharmaceutica Sinica. B · 2024Review
- Review
- Yinchenhao Decoction Protects Against Acute Liver Injury in Mice With Biliary Acute Pancreatitis by Regulating the Gut Microflora-Bile Acids-Liver Axis.Gastroenterology research and practice · 2024Article
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
The gut microbiota participates in the control of energy homeostasis partly through fermentation of dietary fibers hence producing short-chain fatty acids (SCFAs), which in turn promote the secretion of the incretin Glucagon-Like Peptide-1 (GLP-1) by binding to the SCFA receptors FFAR2 and FFAR3 on enteroendocrine L-cells. We have previously shown that activation of the nuclear Farnesoid X Receptor (FXR) decreases the L-cell response to glucose. Here, we investigated whether FXR also regulates the SCFA-induced GLP-1 secretion. GLP-1 secretion in response to SCFAs was evaluated ex vivo in murine colonic biopsies and in colonoids of wild-type (WT) and FXR knock-out (KO) mice, in vitro in GLUTag and NCI-H716 L-cells activated with the synthetic FXR agonist GW4064 and in vivo in WT and FXR KO mice after prebiotic supplementation. SCFA-induced GLP-1 secretion was blunted in colonic biopsies from GW4064-treated mice and enhanced in FXR KO colonoids. In vitro FXR activation inhibited GLP-1 secretion in response to SCFAs and FFAR2 synthetic ligands, mainly by decreasing FFAR2 expression and downstream Gαq-signaling. FXR KO mice displayed elevated colonic FFAR2 mRNA levels and increased plasma GLP-1 levels upon local supply of SCFAs with prebiotic supplementation. Our results demonstrate that FXR activation decreases L-cell GLP-1 secretion in response to inulin-derived SCFA by reducing FFAR2 expression and signaling. Inactivation of intestinal FXR using bile acid sequestrants or synthetic antagonists in combination with prebiotic supplementation may be a promising therapeutic approach to boost the incretin axis in type 2 diabetes.
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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.