Could a metabolite produced in the gut help protect the brain after stroke? Zhang et al. present “Kynurenic acid mitigates post stroke brain damage through the gut-brain neural circuit” via bit.ly/3UXVvLC This study identifies a previously unrecognised gut–brain neural circuit involving kynurenic acid (KYNA). Intestinal KYNA levels were reduced in patients with acute ischaemic stroke, and KYNA levels were associated with neurological recovery at three months in both training and validation cohorts. In experimental stroke models, oral KYNA supplementation improved poststroke cerebral injury by activating GPR35 on enteric neurons and triggering vagal signalling. This pathway ultimately influenced brain regions including the nucleus tractus solitarius, hippocampus and hypothalamus, promoting anti-inflammatory microglial polarisation and enhancing neuronal α7 nicotinic acetylcholine receptor activity. The findings provide striking evidence that intestinal metabolites can influence neurological recovery through a defined gut–brain neural pathway and identify KYNA–GPR35–vagus signalling as a potential therapeutic avenue for stroke recovery. #GutBrainAxis #Microbiome