Dialister -driven succinate accumulation is associated with disease activity and postoperative recurrence in Crohn's disease
Succinate, a metabolite produced by both the gut microbiota and the host, has emerged as a key player in chronic inflammation. In patients with Crohn's disease (CD), increased succinate in the intestinal lumen correlates with both dysbiosis and greater disease activity. To investigate circulati...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:dnet:uabarcelona_::2d50ed12b5cc7c002723826725f1ffa4 |
| Acceso en línea: | https://ddd.uab.cat/record/327818 https://dx.doi.org/urn:doi:10.3748/wjg.v31.i45.112618 |
| Access Level: | acceso abierto |
| Palabra clave: | Crohn's disease Succinate Dialister Biomarker Postoperative recurrence Inflammatory bowel diseases Succinic acid Gut microbiota Prevotella Escherichia coli |
| Sumario: | Succinate, a metabolite produced by both the gut microbiota and the host, has emerged as a key player in chronic inflammation. In patients with Crohn's disease (CD), increased succinate in the intestinal lumen correlates with both dysbiosis and greater disease activity. To investigate circulating succinate as a biomarker of CD activity and its associations with gut microbiota, immune, and clinical features. This study with the prospective inclusion of patients with CD in remission, active CD, and non-inflammatory bowel disease controls matched by age, sex, and body mass index. Remission was defined as Harvey-Bradshaw index < 6, C-reactive protein < 0.4 mg/dL, fecal calprotectin < 250 μg/g, and endoscopic activity index Simple Endoscopic Score for CD < 6. Faecal microbiota profiling was performed using 16S rRNA gene sequencing, and demographic, clinical, and treatment variables were recorded along with blood samples (C-reactive protein and succinate) and stool samples. Results: Succinate levels were significantly elevated in active CD patients compared to inactive patients and non-inflammatory bowel disease controls. These increases were associated with higher Harvey-Bradshaw Index scores, increased expression of the succinate receptor 1 in immune cells, and enrichment of the succinate-producing genus Prevotella and the pro-inflammatory phylum Proteobacteria. Conversely, succinate levels negatively correlated with Odoribacter, a known succinate consumer. Interestingly, Dialister, a slow succinate consumer, was enriched in both active and inactive CD patients and was associated with impaired circulating succinate clearance and increased disease activity as well as postoperative recurrence in a validation cohort. Functional microbial analyses revealed upregulation of fumarate reductase and succinate transporters, alongside reduced NADH dehydrogenase expression, indicating disrupted succinate metabolism. Conclusion: These findings highlight succinate as a promising biomarker for CD activity and progression, suggesting that targeting succinate metabolism or key microbial taxa may offer novel therapeutic opportunities. |
|---|