Succinate’s Dual Roles in Inflammatory Bowel Disease Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Autoimmune Diseases
Autoimmune Diseases
Autoimmune disease is when the immune system mistakenly attacks the body's tissues, often linked to imbalances in the microbiome, which can disrupt immune regulation and contribute to disease development.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This review explores the complex and dual roles of succinate in inflammatory bowel disease (IBD), emphasizing its involvement in the microbiota-metabolism-immune axis. Succinate, a metabolite produced both by host cells and gut microbiota, plays a significant role in IBD by influencing immune responses and metabolic pathways that drive disease progression or promote tissue repair. The review focuses on how succinate’s effects are modulated by its concentration, which can either exacerbate inflammation or support healing processes in the gut.
Who was studied?
The review integrates findings from human clinical studies and preclinical models, including mice and pigs, to explore succinate’s role in IBD. The focus is on the gut microbiota’s influence on succinate production, the effect of succinate on immune cells such as macrophages and T cells, and how succinate’s accumulation in the intestinal lumen correlates with disease activity in IBD patients. This research highlights the specific bacteria involved in succinate metabolism and the subsequent immune responses within the gut, particularly during active disease phases.
Most important findings
Succinate’s role in IBD is context-dependent, with evidence pointing to both pro-inflammatory and anti-inflammatory effects. Elevated succinate levels in IBD patients correlate with more severe disease, as succinate activates immune pathways that exacerbate inflammation. Succinate acts through its receptor, SUCNR1, triggering pro-inflammatory signaling pathways like Wnt/β-catenin and NF-κB, which contribute to intestinal barrier dysfunction, increased fibrosis, and immune cell activation. In contrast, at physiological concentrations, succinate supports tissue repair by promoting anti-inflammatory responses and enhancing epithelial barrier function. The review highlights how the balance between succinate-producing and succinate-consuming bacteria in the gut influences these outcomes. Dysbiosis in IBD patients, particularly the overgrowth of succinate-producing bacteria, contributes to increased succinate levels, exacerbating the disease.
Key implications
The findings suggest that succinate could be a target for therapeutic intervention in IBD. By regulating succinate levels or its signaling pathways, it may be possible to manage the immune responses that drive IBD. Therapies could involve targeting the gut microbiota to balance succinate production and consumption or developing SUCNR1 antagonists to block succinate’s pro-inflammatory effects. Additionally, monitoring succinate levels in patients could provide valuable diagnostic information, allowing for personalized treatment strategies that align with the specific metabolic and immune environment of each patient.