Abstract
Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle within host cells. Succinate is also produced in large amounts during bacterial fermentation of dietary fiber. Elevated succinate levels within the gut lumen have been reported in association with microbiome disturbances (dysbiosis), as well as in patients with inflammatory bowel disease (IBD) and animal models of intestinal inflammation. Recent studies indicate that succinate can activate immune cells via its specific surface receptor, succinate receptor 1(SUCNR1), and enhance inflammation. However, the role of succinate in inflammatory processes within the gut mucosal immune system is unclear. This review includes current literature on the association of succinate with intestinal inflammation and the potential role of succinate–SUCNR1 signaling in gut immune functions.
Highlights
Inflammatory bowel diseases (IBD), which comprise Crohn’s disease (CD) and ulcerative colitis (UC), are chronic relapsing disorders of the gastrointestinal tract that occur with an increasing prevalence and incidence worldwide [1]
Germ‐free mice have little to no detectable succinate in feces relative to conventional mice, indicating that gut microbes are the predominant source of luminal succinate at steady‐state [26,27,28]
Metabolomic studies of the mucosa of IBD patients demonstrated that succinate is increased in inflammatory lesions compared to healthy or control tissue [12,47], and several studies report that fecal succinate concentrations are approximately three to four-fold higher in IBD patients compared to controls (Table 1) [23,48]
Summary
Inflammatory bowel diseases (IBD), which comprise Crohn’s disease (CD) and ulcerative colitis (UC), are chronic relapsing disorders of the gastrointestinal tract that occur with an increasing prevalence and incidence worldwide [1]. While the precise etiology of IBD is unknown, disease is thought to arise from the perturbation of homeostasis between gut-resident microbiota and the mucosal immune system on the background of complex genetic and environmental factors including diet and antibiotic use [2]. The gut microbiota and its metabolic products interact with the host in many different ways to influence homeostasis and disease. Numerous studies support that succinate is not an inert byproduct of metabolism but plays an active role in downstream cellular responses and can have tissue-specific and systemic effects as a proinflammatory mediator [5,6,7,8]. Recent studies indicate an important role for extracellular succinate in the regulation of intestinal immune responses [9,10,11,12]. We will review evidence for the impact of succinate on IBD
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