Barki, N. et al. (2022) Chemogenetics defines the roles of short chain fatty acid receptors within the gut-brain axis. eLife, 11, e73777. (doi: 10.7554/eLife.73777) (PMID:35229717) (PMCID:PMC8887895)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
265414.pdf - Published Version Available under License Creative Commons Attribution. 2MB |
Abstract
Volatile small molecules, including the short-chain fatty acids (SCFAs), acetate and propionate, released by the gut microbiota from the catabolism of nondigestible starches, can act in a hormone-like fashion via specific G-protein-coupled receptors (GPCRs). The primary GPCR targets for these SCFAs are FFA2 and FFA3. Using transgenic mice in which FFA2 was replaced by an altered form called a Designer Receptor Exclusively Activated by Designer Drugs (FFA2-DREADD), but in which FFA3 is unaltered, and a newly identified FFA2-DREADD agonist 4-methoxy-3-methyl-benzoic acid (MOMBA), we demonstrate how specific functions of FFA2 and FFA3 define a SCFA–gut–brain axis. Activation of both FFA2/3 in the lumen of the gut stimulates spinal cord activity and activation of gut FFA3 directly regulates sensory afferent neuronal firing. Moreover, we demonstrate that FFA2 and FFA3 are both functionally expressed in dorsal root- and nodose ganglia where they signal through different G proteins and mechanisms to regulate cellular calcium levels. We conclude that FFA2 and FFA3, acting at distinct levels, provide an axis by which SCFAs originating from the gut microbiota can regulate central activity.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Milligan, Professor Graeme and Hughes, Dr David I and Tobin, Andrew and Bolognini, Dr Daniele and Barki, Ms Natasja and Jenkins, Mrs Laura and Riddell, Professor John and Hudson, Dr Brian |
| Creator Roles: | Barki, N.Conceptualization, Data curation, Investigation, Methodology, Validation, Writing – original draft Tobin, A.Conceptualization, Funding acquisition, Methodology, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review and editing Milligan, G.Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, ["credit_typename_" not defined], Writing – original draft, Writing – review and editing Bolognini, D.Formal analysis, Investigation, Methodology Jenkins, L.Formal analysis, Investigation, Methodology, Validation Hughes, D. I.Investigation, Methodology, Supervision Hudson, B.Methodology Riddell, J.Supervision |
| Authors: | Barki, N., Bolognini, D., Börjesson, U., Jenkins, L., Riddell, J., Hughes, D. I., Ulven, T., Hudson, B. D., Rexen Ulven, E., Dekker, N., Tobin, A. B., and Milligan, G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | eLife |
| Publisher: | eLife Sciences Publications |
| ISSN: | 2050-084X |
| ISSN (Online): | 2050-084X |
| Copyright Holders: | Copyright © 2022 Barki et al |
| First Published: | First published in eLife 11: e73777 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information