Inflammatory bowel disease (IBD) is a chronic, immune-mediated condition characterized by inflammation of the gastrointestinal (GI) tract [1]. The two main forms of IBD, Crohn’s disease (CD) and ulcerative colitis (UC), lead to a variety of symptoms including abdominal pain, diarrhea, fatigue, and weight loss, which greatly impact their quality of life. Although the precise cause of IBD is still unclear, it is thought to result from a disruption in the balance between gut-resident microbiota and the mucosal immune system. This imbalance is driven by a combination of genetic and environmental factors, such as diet and stress [2]. Despite there are several treatments available, still there are up to 50% of patients who do not have a sustained response to current therapies 3•, 4, highlighting the need for a deeper understanding of its pathophysiology.

There is substantial evidence linking IBD to microbial metabolites, which play a crucial role in modulating intestinal health and immune responses [5]. Several studies have demonstrated that IBD patients exhibit alterations in gut microbiota composition, or dysbiosis, which leads to reduced microbial diversity and disruptions in metabolite production. This altered microbial metabolome is increasingly recognized as a potential marker for disease severity and as a target for therapeutic intervention 6, 7, 8. A common trait across both CD and UC is a decrease in beneficial short-chain fatty acid (SCFA)-producing bacteria, such as those that produce butyrate and propionate [9]. These SCFAs have anti-inflammatory properties and are essential for maintaining the integrity of the intestinal barrier [10]. However, despite these shared characteristics, UC and CD present distinct microbial and metabolome signatures [11]. Alterations in secondary bile acids [12], tryptophan-derived metabolites, and microbial-derived polyamines and indole compounds [13], all linked to immune modulation, are implicated in IBD. Among these, succinate stands out as a central player in host and microbial processes 14, 15.

This review examines succinate’s dual role in IBD as a metabolic and signaling molecule, highlighting its contribution to chronic inflammation, gut barrier dysfunction, and fibrosis. It discusses microbial succinate’s role in perpetuating inflammation and dysbiosis, evaluates therapeutic strategies targeting succinate, and explores emerging approaches to reduce succinate levels and modulate the microbiota for improved IBD management.