Metabolic & Cardiometabolic · Gut & Microbiome
intestinal FXR activation suppresses GLP-1
In plain terms: Does the gut bile-acid sensor FXR turn down the appetite-suppressing hormone GLP-1?
Yes — but only shown in animals and the lab so far.
🧭 Read this score with how it was built in mindStudies we had treated as independent turned out to share a research group
Two studies filed separately share a research group. Note this correction moved the verdict UP, not down: the clustered studies were the disconfirming ones, so discounting them let the rest of the evidence carry more weight.
📅 Last reviewed: 2026-07-15 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Animal studies (Animal)
How the studies fall
What the evidence shows
FXR activation represses proglucagon and blunts SCFA-induced GLP-1 (downregulates FFAR2) — the opposing brake to TGR5. Implies BA-binding dietary fiber (lowering luminal FXR tone) could synergize with SCFA production. Animal/cell-grade.
The evidence (14)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Li P, Zhu L, Yang X, Li W, Sun X, Yi B, Zhu S 2019 · J Cell Physiol | in-vitro | supports | moderate | FXR inversely regulates GLP-1 secretion in STC-1 L-cells by inhibiting CREB transcriptional activity. |
| Pathak P, Xie C, Nichols RG, Ferrell JM, Boehme S, Krausz KW, Patterson AD, Gonzalez FJ, Chiang JYL 2018 · (FXR/TauroLCA) | animal | contradicts | moderate | Intestine-restricted FXR agonist fexaramine INCREASED GLP-1 secretion via TGR5; FXR activation raised GLP-1. |
| Zheng X, Chen T, Jiang R, Zhao A, Wu Q, Kuang J, Sun D, Ren Z, Li M, Zhao M, Wang S, Bao Y, Li H, Hu C, Dong B, Li D, Wu J, Xia J, Wang X, Lan K, Rajani C, Xie G, Lu A, Jia W, Jiang C, Jia W 2021 · (HCA) | animal | supports | high | Hyocholic acids raise GLP-1 partly by INHIBITING intestinal FXR (with TGR5 agonism); FXR inhibition boosts GLP-1. |
| Li P, Zhang R, Zhou J, Guo P, Liu Y, Shi S 2024 · Gut Microbes | animal | supports | moderate | Bacterial GUS-driven bile-acid rise activated ileal FXR and suppressed L-cell GLP-1 |
| Trabelsi MS, Daoudi M, Prawitt J, Ducastel S, Touche V, Sayin SI, Perino A, Brighton CA, Sebti Y, Kluza J, Briand O, Dehondt H, Vallez E, Dorchies E, Baud G, Spinelli V, Hennuyer N, Caron S, Bantubungi K, Caiazzo R, Reimann F, Marchetti P, Lefebvre P, Bäckhed F, Gribble FM, Schoonjans K, Pattou F, Tailleux A, Staels B, Lestavel S 2015 · Nat Commun | animal | supports | high | Landmark FXR in L-cells represses proglucagon+GLP-1; FXR-KO raises GLP-1 (in-vitro+mouse) |
| Ducastel S, Touche V, Trabelsi MS, Boulinguiez A, Butruille L, Nawrot M, Peschard S, Chávez-Talavera O, Dorchies E, Vallez E, Annicotte JS, Lancel S, Briand O, Bantubungi K, Caron S, Bindels LB, Delzenne NM, Tailleux A, Staels B, Lestavel S 2020 · Sci Rep | animal | supports | high | FXR blunts SCFA-induced GLP-1 by lowering FFAR2 (colonoids+L-cells+mice); FXR-KO raises FFAR2+GLP-1 |
| Stefela A, Kaspar M, Drastik M, Kronenberger T, Micuda S, Dracinsky M, Klepetarova B, Kudova E, Pavek P 2021 · Front Pharmacol | in-vitro | mixed | low | Dual FXR antagonist/GPBAR1 agonist 7-ELCA stimulates GLP-1 from enteroendocrine cells; FXR blockade favors GLP-1. |
| Pathak P, Liu H, Boehme S, Xie C, Krausz KW, Gonzalez F, Chiang JYL 2017 · J Biol Chem | animal | contradicts | moderate | Dual FXR/TGR5 agonist INT-767 stimulated intestinal GLP-1 secretion; FXR activation augmented GLP-1. |
| Yun C, Yan S, Liao B, Ding Y, Qi X, Zhao M, Wang K, Zhuo Y, Nie Q, Ye C, Xia P, Ma M, Li R, Jiang C, Qiao J, Pang Y 2024 · Nat Metab | animal | supports | high | Yun 2024 NatMetab microbial agmatine FXR agonist promoting PCOS mice; confirms FXR-axis. ANIMAL |
| Lv J, Zhou L, Dai X, Landberg R, Meng H, Tian H, Zhang S, Liu T, Yin X, Zhang J, Song X, Bonny C, Blum S, Cao Y, Guo J, Peng W, Tan Y, Shi L 2026 · Gut microbes | animal | supports | moderate | Mouse HFD model: BSH-driven UDCA acts as intestinal FXR antagonist + TGR5 agonist, stimulating GLP-1 secretion; GR-7 BSH-inhibitor lowered UDCA and GLP-1. |
| Sun YH, Ding PL, Wang X, Wang YR, Zhu MZ, Wang K, Dai L, Dang YQ, Ji G, Li M, Zhou WJ 2026 · Pharmaceuticals (Basel, Switzerland) | animal | supports | low | HFD mouse model: LGZG inhibited intestinal FXR-Fgf15 axis while enriching TGR5-agonist/FXR-antagonist bile acids, raising serum GLP-1 (p<0.05) via TGR5, not FXR activation. |
| Stefela A, Dohnalova K, Lastuvkova H, Skoda J, Bajnokova M, Lestavel S, Touche V, Kaspar M, Kudova E, Hroch M, Micuda S, Kucera O, Pavek P 2025 · Pharmacol Res | animal | supports | moderate | FXR antagonist enhanced GLP-1 secretion and improved glucose metabolism in Western-diet mice |
| Niss K, Jakobsson ME, Westergaard D, Belling KG, Olsen JV, Brunak S 2020 · Mol Cell Endocrinol | in-vitro | supports | moderate | Niss 2020 GLUTag L-cell active FXR represses GLP-1 secretion |
| Kim KS, Peck BC, Hung YH, Koch-Laskowski K, Wood L, Dedhia PH, Spence JR, Seeley RJ, Sethupathy P, Sandoval DA 2022 · JCI Insight | animal | contradicts | moderate | FXR agonists increased GLP-1+ enteroendocrine cell number/differentiation in intestinal organoids; activation raised GLP-1. |
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