ArticleNature communications2026
Kynurenine mediates the chemotherapy-induced intestinal toxicity through modulation of gut microbiota.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Microbiota-Associated Amino Acid Metabolites in Inflammatory Bowel Disease: Emerging Key Players in the Host-Microbe Interface.Microorganisms · 2026Review
- Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.Clinical and translational medicine · 2026Review
- A circuit linking dentate gyrus and retrosplenial granular cortex regulates fracture healing in male mice.Nature communications · 2026Article
- Beyond antibiotics: collateral damage to the gut microbiome during cancer therapy.Frontiers in microbiology · 2026Review
- Mechanisms by which complex carbohydrates influence immune imbalance in COPD via the gut-lung axis: from colonic fermentation to pulmonary immune responses.Frontiers in nutrition · 2026Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy-induced intestinal toxicity is a major dose-limiting complication, but the underlying mechanisms linking systemic metabolism to localized gut damage are poorly understood. Here we show that serum L-kynurenine, a tryptophan metabolite, is elevated in patients with severe oxaliplatin-induced intestinal toxicity. Accumulation of L-kynurenine is driven by IFNγ-mediated induction of indoleamine 2,3-dioxygenase 1 (IDO1) in myeloid cells. Using scRNA-seq and myeloid cell-specific knockout models, we confirm that myeloid cell-derived L-kynurenine exacerbates toxicity. Critically, L-kynurenine accumulation drives gut dysbiosis, characterized by the loss of Lactobacillus johnsonii, and subsequently activates the TNFα/JNK pathway, leading to intestinal epithelial apoptosis. Pharmacological inhibition or engineered reduction of L-kynurenine mitigates chemotherapy-induced intestinal injury. Our findings reveal an important role of L-kynurenine from myeloid cells in chemotherapy tolerance and propose its targeting as a potential therapeutic strategy.
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Registered trials
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