ArticleNature communications2025
Microbiota-indole-3-propionic acid-heart axis mediates the protection of leflunomide against αPD1-induced cardiotoxicity in mice.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Skeletal muscle metabolomic markers underlying the enhanced exercise-induced hypertrophy response to resistance training in older adults.GeroScience · 2026Article
- Gut microbiome shifts in chronic systolic heart failure are associated with disease severity and clinical improvement.Nature cardiovascular research · 2026Article
- Gut Microbiota-Derived Indole-3-Propionic Acid Alleviates Diabetic Osteoporosis Through Nrf2-Mediated Ferroptosis Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The gut microbiome and allograft outcomes: implications for heart transplantation.The Journal of clinical investigation · 2026Review
- Review
- Microbiota and immune-related adverse events in cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Dietary fiber intake and mortality among adults with hyperlipidemia : a retrospective cohort analysis from NHANES 1999-2018.Lipids in health and disease · 2026Article
- Article
- Immune checkpoint inhibition and heart injury: molecular mechanisms and clinical challenges.ESC heart failure · 2026Review
- Associations Between Gut Microbiota and Mitochondrial Metabolites, with Growth Differentiation Factor-15 as a Marker of Oxidative Stress in Heart Failure vs. Healthy Ageing.Antioxidants (Basel, Switzerland) · 2026Article
- Multi-omics analysis identifies stemness-driven molecular subtypes, prognostic signature, epigenetic target APCDD1, and drug candidate Leflunomide in Wilms tumor.Frontiers in oncology · 2026Article
- Ferroptosis regulation in doxorubicin-induced cardiotoxicity: multi-mechanism interventions and translational strategies.Frontiers in pharmacology · 2026Review
- Navigating the gut-metabolite-immune axis: enhancing efficacy and mitigating toxicity of immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- Article
- Bacterial tryptophan metabolites in cancer and atherosclerosis: insights for a role in immune checkpoint inhibition.Essays in biochemistry · 2025Review
- Oral Multi-Enzymatic Manganese-Carbon Dots Alleviate Sepsis-Associated Lung Injury via the Gut-Lung Axis.ACS nano · 2025Article
- Indole Propionic Acid Regulates Gut Immunity: Mechanisms of Metabolite-Driven Immunomodulation and Barrier Integrity.Journal of microbiology and biotechnology · 2025Review
- Metabolic interactions: how gut microbial metabolites influence colorectal cancer.Frontiers in microbiology · 2025Review
- The bidirectional regulatory mechanism of gut microbiota metabolites on myocardial injury in heart failure from the perspective of the gut-heart axis: a review.Frontiers in microbiology · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Anti-programmed death 1 (αPD1) immune checkpoint blockade is used in combination for cancer treatment but associated with cardiovascular toxicity. Leflunomide (Lef) can suppress the growth of several tumor and mitigate cardiac remodeling in mice. However, the role of Lef in αPD1-induced cardiotoxicity remains unclear. Here, we report that Lef treatment inhibits αPD1-related cardiotoxicity without compromising the efficacy of αPD1-mediated immunotherapy. Lef changes community structure of gut microbiota in αPD1-treated melanoma-bearing mice. Moreover, mice receiving microbiota transplants from Lef+αPD1-treated melanoma-bearing mice have better cardiac function compared to mice receiving transplants from αPD1-treated mice. Mechanistically, we analyze metabolomics and identify indole-3-propionic acid (IPA), which protects cardiac dysfunction in αPD1-treated mice. IPA can directly bind to the aryl hydrocarbon receptor and promote phosphoinositide 3-kinase expression, thus curtailing the cardiomyocyte response to immune injury. Our findings reveal that Lef mitigates αPD1-induced cardiac toxicity in melanoma-bearing mice through modulation of the microbiota-IPA-heart axis.
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