ArticleCellular & molecular biology letters2025
GPR43 deficiency aggravates sepsis by promoting gut microbiota-dependent barrier disruption and HIF-1α-ENO1 axis-mediated M1 polarization of macrophages.
Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- CD47-mediated efferocytosis in diseases: A comprehensive review.Molecular biology reports · 2026Review
- Short-Chain Fatty Acids in Sepsis: Mechanisms of Action and Therapeutic Advances.Biomedicines · 2026Review
- Enolase-1 and Inflammation.Biomolecules · 2026Review
- ENO1 as an Immunoregulatory Hub in Cancer: Mechanisms and Translational Implications.Biomolecules · 2026Review
- Integrated Single-Cell and Spatial Analysis Reveals a Metabolic-Immune Axis Driving Aortic Dissection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- The progress of mitochondrial function and transfer in stem cell regulation and therapy.Journal of physiology and biochemistry · 2026Review
- Mutation mapping and functional characterization of a missense mutation p.Arg228Cys in ALDH3A2 gene causing Sjögran-Larson syndrome.Molecular biology reports · 2026Article
- Gut microbiota dysbiosis in sepsis and sepsis-associated organ injury: mechanisms, gut-organ axes, and therapeutic strategies.Frontiers in microbiology · 2026Review
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15 authors.
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Abstract
backgroundGPR43, a receptor for short-chain fatty acids (SCFAs), is broadly expressed in intestinal epithelial and immune cells and is essential for preserving barrier integrity and immune homeostasis. Nevertheless, how GPR43 influences gut microbiota composition and intestinal barrier integrity while also regulating macrophage immunometabolism in the context of sepsis remains poorly understood.
methodsA cecal ligation and puncture model was used to induce sepsis in mice. Survival, histopathology, and immune responses were compared between Gpr43−/− and wild-type mice; 16S ribosomal RNA (rRNA) sequencing and untargeted metabolomics were performed to evaluate gut microbiota composition and metabolic profiles. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation were used to assess functional impacts. Bone marrow-derived macrophages were employed to investigate the effects of GPR43 deficiency on macrophage polarization. RNA sequencing, metabolic flux analysis, and Western blotting were conducted to explore the molecular mechanisms involved. Peripheral blood mononuclear cell samples from patients with sepsis were analyzed for clinical correlation.
resultsGpr43−/− mice exhibited significantly reduced survival following CLP, along with impaired intestinal barrier function and elevated proinflammatory cytokine levels. Microbiota diversity and SCFA-producing bacteria were markedly decreased, accompanied by reduced SCFA levels in fecal metabolites. Fecal microbiota transplantation (FMT) partially restored gut function and survival in Gpr43−/− mice. GPR43-deficient macrophages displayed a strong M1-polarized phenotype with the upregulation of the glycolytic enzyme ENO1 and its upstream regulator HIF-1α. The inhibition of either ENO1 or HIF-1α reversed the proinflammatory phenotype. A clinical data analysis revealed that GPR43 expression was negatively correlated with IL-6, ENO1, and lactate levels.
conclusionsGPR43 exerts a dual protective role in sepsis by maintaining gut microbiota homeostasis and barrier integrity and by modulating macrophage metabolism and polarization via the HIF-1α–ENO1 axis. This study provides novel insights into the GPR43 in pathogenesis of sepsis and suggests potential therapeutic targets for intervention.
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