ArticleHepatology (Baltimore, Md.)2018
Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 321 papers, 3 of them syntheses that pooled it.
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Who cites it
321 citing papers in PubMed, 3 syntheses or guidelines pooled it, 521 citations in OpenAlex.
- Effects of Weight Loss Interventions on Gut Microbiota-Derived Metabolites Linked to Cardiometabolic Health: A Systematic Review and Meta-Analysis.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Pooled it
- Global bibliometric analysis of traditional Chinese medicine regulating gut microbiota in the treatment of diabetes from 2004 to 2024.Frontiers in pharmacology · 2025Pooled it
- Roles of the gut microbiome in weight management.Nature reviews. Microbiology · 2023Pooled it
- Changes in bile acid subtypes and improvements in lipid metabolism and atherosclerotic cardiovascular disease risk: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial.The American journal of clinical nutrition · 2024Trial
- The gut microbiome-bile acid-FXR interplay: a pivotal axis in metabolic and gastrointestinal diseases.Gut microbes · 2026Review
- Intestinal FXR agonism synergizes with leptin to improve obesity by reducing appetite via secretin.EMBO reports · 2026Article
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Gut‑liver‑kidney axis: A systems biology framework for understanding and treating chronic kidney disease (Review).International journal of molecular medicine · 2026Review
- Chronic administration of a calafate (Berberis microphylla) polyphenol-rich extract modulates gut microbiota and metabolic homeostasis associated with thermogenic activation in high-fat diet-fed mice.Journal of physiology and biochemistry · 2026Article
- Foods as Modulators of GLP-1 Secretion.Nutrients · 2026Review
- SMRT regulation of nuclear receptors orchestrates bile acid homeostasis.Experimental & molecular medicine · 2026Article
- Grain proteins ameliorate glucose metabolism disorders by activating intestinal AhR and the hepatic NLK/FOXO1 pathway via gut microbiota-derived indole metabolites.Journal of advanced research · 2026Article
- Nanocellulose Alleviates Intrahepatic Cholestasis of Pregnancy via Gut Microbiota-Mediated Bile Acid Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microbiome and aging: Trajectories of microbiome age across human ecosystems and their systemic effects.iMeta · 2026Review
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- Article
- Adipose Tissue Browning in MASLD and Its Molecular Mechanisms and Metabolic Crosstalk.Current obesity reports · 2026Review
- Mechanism-First Psychobiotics: Fermented Vegetables, Dairy, and Soy for Depression and Anxiety.International journal of molecular sciences · 2026Review
- Intestinal FXR deficiency uncouples steatosis protection from liver inflammation and fibrosis in MASH-diet fed mice.Scientific reports · 2026Article
- Phytochemicals remodel antitumor immunity via the "microbiota-metabolite-receptor" axis: focus on colorectal cancer and immunotherapy.Medical oncology (Northwood, London, England) · 2026Review
261 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Bile acids activate farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (aka Takeda G protein-coupled receptor-5 [TGR5]) to regulate bile acid metabolism and glucose and insulin sensitivity. FXR and TGR5 are coexpressed in the enteroendocrine L cells, but their roles in integrated regulation of metabolism are not completely understood. We reported recently that activation of FXR induces TGR5 to stimulate glucagon-like peptide-1 (GLP-1) secretion to improve insulin sensitivity and hepatic metabolism. In this study, we used the intestine-restricted FXR agonist fexaramine (FEX) to study the effect of activation of intestinal FXR on the gut microbiome, bile acid metabolism, and FXR and TGR5 signaling. The current study revealed that FEX markedly increased taurolithocholic acid, increased secretion of fibroblast growth factors 15 and 21 and GLP-1, improved insulin and glucose tolerance, and promoted white adipose tissue browning in mice. Analysis of 16S ribosomal RNA sequences of the gut microbiome identified the FEX-induced and lithocholic acid-producing bacteria Acetatifactor and Bacteroides. Antibiotic treatment completely reversed the FEX-induced metabolic phenotypes and inhibited taurolithocholic acid synthesis, adipose tissue browning, and liver bile acid synthesis gene expression but further increased intestinal FXR target gene expression. FEX treatment effectively improved lipid profiles, increased GLP-1 secretion, improved glucose and insulin tolerance, and promoted adipose tissue browning, while antibiotic treatment reversed the beneficial metabolic effects of FEX in obese and diabetic mice.
conclusionThis study uncovered a mechanism in which activation of intestinal FXR shaped the gut microbiota to activate TGR5/GLP-1 signaling to improve hepatic glucose and insulin sensitivity and increase adipose tissue browning; the gut microbiota plays a critical role in bile acid metabolism and signaling to regulate metabolic homeostasis in health and disease. (Hepatology 2018).
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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.