Microbial products trigger chemosensory dialogues through intestinal G protein-coupled receptors.

A cyclic fatty acid activates intestinal serotonin production from enterochromaffin cells through olfactory receptor OR51E1, revealing a gut chemosensory pathway.

• Why it matters: Organisms need information relays that detect environmental cues and coordinate responses, but the specific intestinal GPCR pathways sensing microbial products remain unclear.
• What they did: Using GPCR-seq to screen libraries of gut metabolites and natural products, the study identified OR51E1 as mediating serotonin output and found β-carboline and 6-hydroxynicotinic acid (6-HNA) as GPR35 agonists.
• The result: The IBD-linked GPR35 variant T108M shows aberrant responses to 6-HNA, and Enterocloster bolteae generates high levels of 6-HNA, enabling faster mapping of host chemosensory responses.

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