Bile acid signaling pathways from the enterohepatic circulation to the central nervous system
Open accessAbstract
Bile acids are best known as detergents involved in the digestion of lipids. In addition, new data in the last decade have shown that bile acids also function as gut hormones capable of influencing metabolic processes via receptors such as FXR (farnesoid X receptor) and TGR5 (Takeda G protein-coupled receptor 5). These effects of bile acids are not restricted to the gastrointestinal tract, but can affect different tissues throughout the organism. It is still unclear whether these effects also involve signaling of bile acids to the central nervous system (CNS). Bile acid signaling to the CNS encompasses both direct and indirect pathways. Bile acids can act directly in the brain via central FXR and TGR5 signaling. In addition, there are two indirect pathways that involve intermediate agents released upon interaction with bile acids receptors in the gut. Activation of intestinal FXR and TGR5 receptors can result in the release of fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1), both capable of signaling to the CNS. We conclude that when plasma bile acids levels are high all three pathways may contribute in signal transmission to the CNS. However, under normal physiological circumstances, the indirect pathway involving GLP-1 may evoke the most substantial effect in the brain.
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BA receptors are present in the brain, and BAs can be synthesized locally or actively transported across the BBB by BA transporters from circulation.
“BA receptors are present in the brain, and BAs can either be synthesized locally or actively transported across the BBB by BA transporters from circulation (297, 301, 302).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [297]
BAs are important modulators of the MGB axis, functioning directly via BA receptors in the ENS and brain or indirectly via GLP-1 or the FXR-FGF15/19 axis.
“these metabolites have emerged as important modulators of the MGB axis, functioning directly via BA receptors in the ENS and brain or indirectly via GLP-1 or the FXR-FGF15/19 axis (297, 319).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [297]
Some reports suggest bile acids can cross the blood-brain barrier, whereas other bile acid conjugates signal directly to the brain as neuroactive ligands by binding FXR and TGR5 in the CNS or indirectly by binding these receptors in the gastrointestinal tract and initiating a signaling cascade.
“Some reports suggest that bile acids can cross the BBB, whereas other bile acid conjugates have been shown to signal directly to the brain as neuroactive ligands, either by binding to farnesoid X receptor and Takeda G protein-coupled receptor 5 (TGR5) present in the CNS or indirectly by binding these receptors in the gastrointestinal tract and initiating a signaling cascade (411).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [411]
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The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
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- Authors
- Mertens, K. L., Kalsbeek, A., Soeters, M. R., & Eggink, H. M.
- Affiliations
- University of Amsterdam (NL)
- Netherlands Institute for Neuroscience (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Eggink, Hannah M.
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2017-11-07
- Volume
- 11
- Pages
- 617-617
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC5681992
- OpenAlex
- W2767947916
- Cited by
- 287
- References
- 195
- Citations by year
- 2026: 25 · 2025: 35 · 2024: 39 · 2023: 30 · 2022: 56 · 2021: 34 · 2020: 35 · 2019: 21 · 2018: 11 · 2017: 1
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Funders
- Diabetes Fonds (2011.80.1423)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Keywords
- bile acids, enterohepatic circulation, central nervous system, farnesoid X receptor, TGR5, FGF19, glucagon-like peptide-1, gut-brain signaling, bile acid receptors, gastrointestinal hormones
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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