The role of microbial succinate in the pathophysiology of inflammatory bowel disease: mechanisms and therapeutic potential

Autor segons l'article: Fernandez-Veledo, Sonia; Grau-Bove, Carme; Notararigo, Sara; Huber-Ruano, Isabel

Departament: Ciències Mèdiques Bàsiques

Autor/s de la URV: Fernandez Veledo, Sonia

Paraules clau: Triggers; Mic; Macrophages; Gut microbiota; Colitis; Cells

Resum: Inflammatory bowel disease (IBD) is a chronic immune-mediated condition linked to gut microbiota dysbiosis and altered production of bacterial metabolites, including succinate, which is also a key intermediate in human mitochondrial energy metabolism in human cells. Succinate levels in the gut are influenced by microbial community dynamics and cross-feeding interactions, highlighting its dual metabolic and ecological importance. Extracellular succinate acts as a key signaling metabolite linking microbial metabolism to host physiology, with transient rises supporting metabolic regulation but chronic elevations contributing to metabolic disorders and disease progression. Succinate signals through its cognate receptor SUCNR1, which mediates adaptive metabolic responses under normal conditions but drives inflammation and fibrosis when dysregulated. IBD patients display a dysbiotic gut microbiota characterized by an increased prevalence of succinate-producing bacteria, contributing to elevated succinate levels in the gut and circulation. This imbalance drives inflammation, worsens IBD severity, and contributes to complications like Clostridioides difficile infection and fibrosis. Emerging evidence highlights the potential of intestinal and systemic succinate levels as indicators of microbial dysbiosis, with a bidirectional relationship between microbial composition and succinate metabolism. Understanding the factors influencing succinate levels and their interaction with dysbiosis shows promise in the development of therapeutic strategies to restore microbial balance. Approaches such as dietary fiber enrichment, prebiotics, and probiotics to enhance succinate-consuming bacteria, combined with targeted modulation of succinate pathways (e.g. SDH inhibitors, SUCNR1 antagonists), hold promise for mitigating inflammation and improving gut health in IBD.

Àrees temàtiques: Microbiology (medical); Microbiology; Medicina ii; Medicina i; Infectious diseases; Farmacia; Ciências biológicas iii; Ciências biológicas ii; Ciências biológicas i; Ciência da computação

Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/

Adreça de correu electrònic de l'autor: sonia.fernandez@urv.cat; sonia.fernandez@urv.cat

Data d'alta del registre: 2025-04-30

Versió de l'article dipositat: info:eu-repo/semantics/submittedVersion

Enllaç font original: https://www.sciencedirect.com/science/article/abs/pii/S1369527425000219

Referència a l'article segons font original: Current Opinion In Microbiology. 85 102599-

Referència de l'ítem segons les normes APA: Fernandez-Veledo, Sonia; Grau-Bove, Carme; Notararigo, Sara; Huber-Ruano, Isabel (2025). The role of microbial succinate in the pathophysiology of inflammatory bowel disease: mechanisms and therapeutic potential. Current Opinion In Microbiology, 85(), 102599-. DOI: 10.1016/j.mib.2025.102599

URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/

DOI de l'article: 10.1016/j.mib.2025.102599

Entitat: Universitat Rovira i Virgili

Any de publicació de la revista: 2025

Tipus de publicació: info:eu-repo/semantics/preprint