| First Author | Cheng L | Year | 2024 |
| Journal | Cell Host Microbe | Volume | 32 |
| Issue | 2 | Pages | 227-243.e6 |
| PubMed ID | 38198925 | Mgi Jnum | J:346162 |
| Mgi Id | MGI:7613877 | Doi | 10.1016/j.chom.2023.12.009 |
| Citation | Cheng L, et al. (2024) A Gpr35-tuned gut microbe-brain metabolic axis regulates depressive-like behavior. Cell Host Microbe 32(2):227-243.e6 |
| abstractText | 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(-/-) mice and individuals with depression have increased Parabacteroides distasonis, and its colonization to wild-type mice induces depression. Gpr35(-/-) 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. |
