传统中药方剂“肠康方”通过乳酸菌-吲哚-3-乳酸-芳香烃受体/白介素-22轴路，恢复肠易激综合征（IBS-D）患者肠道-大脑稳态。

Abstract

CKF ameliorates intestinal dysfunction and neurobehavioral abnormalities in IBS-D mice. • CKF boosts L. johnsonii and tryptophan-derived indoles, notably ILA. • L. johnsonii acts as a psychobiotic for IBS-D and comorbidities. • ILA improves IBS-D intestinal and behavioral deficits mainly via AhR activation. • CKF targets the L. johnsonii -ILA-AhR/IL-22 gut-brain axis. Background Gut dysbiosis contributes to irritable bowel syndrome (IBS) by disrupting intestinal barrier functions and promoting inflammation. Chang‑kang‑fang (CKF), a Chinese herbal formula proven effective for diarrhea‑predominant IBS (IBS‑D) in a phase III trial, is thought to modulate the gut microbiota, yet the underlying mechanism remains unclear. Purpose To elucidate how CKF ameliorates IBS‑D by modulating the gut microbiota. Methods IBS‑D was induced by restraint stress, tail pinch, and senna gavage. Intestinal function, inflammation, and behavior were evaluated. Gut microbiota and metabolites were profiled via 16S rRNA sequencing and metabolomics. FMT confirmed the causal involvement of the microbiota. The key microbe and metabolite were validated in vivo . Mechanistic analyses evaluated intestinal barrier integrity, systemic inflammation, hippocampal blood‑brain barrier (BBB) function, neuroinflammation, and synaptic plasticity. Results CKF alleviated diarrhea, visceral hypersensitivity, inflammation, barrier dysfunction, and anxiety‑ and depression‑like behaviors. These benefits were associated with gut microbiota remodeling, featuring enrichment of Lactobacillus johnsonii and enhanced tryptophan metabolism. FMT confirmed that this microbial remodeling mediates the therapeutic effects of CKF. Supplementation with L. johnsonii or its metabolite indole‑3‑lactic acid (ILA) largely recapitulated these gut-brain benefits via AhR/IL‑22 activation. Mechanistically, CKF‑induced L. johnsonii enrichment activated the ILA-AhR-IL‑22 pathway, which enhanced intestinal and BBB integrity, there