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A Gpr35-tuned gut microbe-brain metabolic axis regulates depressive-like behavior.
- Source :
-
Cell host & microbe [Cell Host Microbe] 2024 Feb 14; Vol. 32 (2), pp. 227-243.e6. Date of Electronic Publication: 2024 Jan 09. - Publication Year :
- 2024
-
Abstract
- Gene-environment interactions shape behavior and susceptibility to depression. However, little is known about the signaling pathways integrating genetic and environmental inputs to impact neurobehavioral outcomes. We report that gut G-protein-coupled receptor, Gpr35, engages a microbe-to-brain metabolic pathway to modulate neuronal plasticity and depressive behavior in mice. Psychological stress decreases intestinal epithelial Gpr35, genetic deletion of which induces depressive-like behavior in a microbiome-dependent manner. Gpr35 <superscript>-/-</superscript> mice and individuals with depression have increased Parabacteroides distasonis, and its colonization to wild-type mice induces depression. Gpr35 <superscript>-/-</superscript> and Parabacteroides distasonis-colonized mice show reduced indole-3-carboxaldehyde (IAld) and increased indole-3-lactate (ILA), which are produced from opposing branches along the bacterial catabolic pathway of tryptophan. IAld and ILA counteractively modulate neuroplasticity in the nucleus accumbens, a brain region linked to depression. IAld supplementation produces anti-depressant effects in mice with stress or gut epithelial Gpr35 deficiency. Together, these findings elucidate a gut microbe-brain signaling mechanism that underlies susceptibility to depression.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Bacteroidetes
Brain
Gastrointestinal Microbiome physiology
Microbiota
Subjects
Details
- Language :
- English
- ISSN :
- 1934-6069
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell host & microbe
- Publication Type :
- Academic Journal
- Accession number :
- 38198925
- Full Text :
- https://doi.org/10.1016/j.chom.2023.12.009