ArticleCell communication and signaling : CCS2025
Indole-3-lactic acid protects the gut vascular barrier following intestinal ischemia injury through AhR/Nrf2/STAT3 mediated claudin 2 downregulation.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- Gut microbiota and immunometabolism in obesity.Gut microbes · 2026Review
- Limosilactobacillus reuteri orchestrates IAA-mediated mitochondrial homeostasis and stem cell renewal against intestinal oxidative injury in aged hens.Journal of animal science and biotechnology · 2026Article
- Glycyrrhizic Acid Alleviates Atherosclerosis inInternational journal of molecular sciences · 2026Article
- The Gut-Pancreas Axis in Type 1 Diabetes: Emerging Insights into Microbiota and Immune Interactions.International journal of molecular sciences · 2026Review
- The gut microbiota-metabolite-target axis in insomnia: network pharmacology and gut microbiota profiling insights into pathogenesis and intervention with Cinnamomi Cortex-Gardeniae Fructus.Frontiers in microbiology · 2026Article
- Mechanisms by which tryptophan metabolites enhance intestinal barrier function to prevent necrotizing enterocolitis in preterm infants.Frontiers in immunology · 2026Review
- Gut microbiota and microbiota-derived metabolites in radiation-induced injury: mechanisms and therapeutic opportunities.Frontiers in microbiology · 2026Review
- Intestinal Ischemia/Reperfusion Injury: Mechanisms, Diagnosis, and Therapeutic Advances.International journal of biological sciences · 2026Review
- Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis.International journal of biological sciences · 2026Review
- Gut microbiota-derived tryptophan metabolites: molecular mechanisms, nutritional strategies and implications for swine health.Frontiers in veterinary science · 2026Review
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11 authors.
Funding
Abstract
BACKGROUND &
aimsDysfunction of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) contributes to the development of intestinal ischemia/reperfusion (IR) injury. Tryptophan (TRP), an essential amino acid, plays a crucial role in maintaining intestinal homeostasis, yet its regulatory effects on the GVB following IR remain unexplored. We aimed to better define the role of TRP in intestinal IR in vivo and in vitro.
methodsMice underwent intestinal ischemia/reperfusion (IR) and were fed control, TRP-recommended (TRP-r), or TRP-sufficient (TRP-s) diets. Fecal metagenomic sequencing analyzed microbial composition, and targeted metabolomics quantified tryptophan and its metabolites in intestinal and serum samples. ILA's effects on barrier integrity were assessed via tight junction protein expression and FITC-dextran permeability assays. RNA sequencing of intestinal endothelial cells elucidated mechanisms by which ILA modulated GVB function. The STAT3-claudin 2 relationship was validated in vitro by ChIP-qPCR.
resultsTRP supplementation significantly reshaped the gut microbiota, mitigated tissue damage and enhanced the integrity of both the IEB and GVB. Indole-3-lactic acid (ILA), a key tryptophan metabolite, was identified as an important factor in preserving GVB function. Mechanistically, our results show that the aryl hydrocarbon receptor (AhR)/Nrf2/signal transducer and activator of transcription 3 (STAT3) pathway is essential for ILA-mediated improvement of GVB integrity and downregulation of the pore-forming protein claudin 2.
conclusionsOur findings highlight the dual role of ILA in reinforcing both IEB and GVB functions and shed light on the molecular mechanisms underlying ILA's GVB-protective effects. This study implicates that ILA or other AhR-activating metabolites may serve as promising pharmacological agents for alleviating IR-induced intestinal damage.
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