Article Synopsis
- The gut microbiota significantly influences gut health through metabolite composition, especially the pro-inflammatory metabolite succinate.
- It was discovered that pro-inflammatory macrophages increase succinate uptake via sodium-dependent transporters, which are present in both macrophages and epithelial cells.
- In individuals with inflammatory bowel diseases (IBDs), higher levels of succinate in feces and serum were linked to changes in gut bacteria that metabolize succinate, indicating a potential breakdown in the mechanism that normally regulates succinate absorption and delivery during inflammation.
Video Abstracts
Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The gut metabolite composition determined by the microbiota has paramount impact on gastrointestinal physiology. However, the role that bacterial metabolites play in communicating with host cells during inflammatory diseases is poorly understood. Here, we aim to identify the microbiota-determined output of the pro-inflammatory metabolite, succinate, and to elucidate the pathways that control transepithelial succinate absorption and subsequent succinate delivery to macrophages. We show a significant increase of succinate uptake into pro-inflammatory macrophages, which is controlled by Na-dependent succinate transporters in macrophages and epithelial cells. Furthermore, we find that fecal and serum succinate concentrations were markedly augmented in inflammatory bowel diseases (IBDs) and corresponded to changes in succinate-metabolizing gut bacteria. Together, our results describe a succinate production and transport pathway that controls the absorption of succinate generated by distinct gut bacteria and its delivery into macrophages. In IBD, this mechanism fails to protect against the succinate surge, which may result in chronic inflammation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2021.109521 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Betanin and vanillic acid reduce bleomycin-induced mitochondrial dysfunction in rat lung isolated mitochondria; a hormetic mode of action for vanillic acid.
Toxicol Mech Methods
September 2025
Lung Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Mechanistic studies have been suggested that toxic effects of bleomycin are generally attributed to formation of free radicals, mitochondria damages, oxidative stress and inflammation. For this purpose, we explored the direct exposure of bleomycin and protective effects of the betanin and vanillic acid separately against its possible toxicity in rat lung isolated mitochondria. Various mitochondrial toxicity parameters were evaluated including; succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial swelling, mitochondrial membrane potential (MMP) collapse, malondialdehyde (MDA) and glutathione disulfide (GSSG) levels.
View Article and Find Full Text PDFRisk assessment and underlying mechanisms of pydiflumetofen resistance in Alternaria tenuissima and Alternaria alternata.
Pestic Biochem Physiol
November 2025
State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China; Department of Plant Pathology, College of Plant Protection, China Agricultural University, 2 Yuanmingyuanxi Road, Beijing 100193, Ch
Potato early blight is a prevalent disease that significantly impacts potato cultivation. Pydiflumetofen, a new succinate dehydrogenase inhibitor developed by Syngenta, has been registered for use on multiple crops in China. However, its resistance risk and mechanisms in Alternaria tenuissima and Alternaria alternata are still poorly understood.
View Article and Find Full Text PDFThe nitrogen regulator AreA modulates lipid metabolism through uga2 in Mucor circinelloides.
Fungal Biol
October 2025
Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, 255000, Shandong, China; School of Basic Medicine, Qilu Medical University, Zibo, 255300, Shandong, China. Electronic address:
Oleaginous filamentous fungus Mucor circinelloides harbors a GATA transcription activator AreA, which regulates nitrogen metabolism. In our previous study, deletion of AreA resulted in increased lipid production, while its overexpression reduced lipid synthesis. Although it is not a direct lipogenesis regulator, AreA influences metabolic flux by modulating nitrogen utilization pathways, which in turn affects carbon distribution.
View Article and Find Full Text PDFMetabolic Profiling Reveals a Glycolytic Shift and an IRG1/Itaconate/NF2L2 Axis Regulating Neurotoxic Oxidative Stress in Inflammatory Microglia.
J Neurochem
September 2025
Toxicology Unit, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Polar metabolic profiling, as well as bioenergetic assays, were used to characterize microglial responses to lipopolysaccharide, which induces a pro-inflammatory state, and interleukin-4, which is associated with an anti-inflammatory phenotype. BV2 microglial cells and primary microglia were used for these investigations. Results revealed that lipopolysaccharide-treated microglia exhibited an increased aerobic glycolytic activity measured by extracellular flux analysis, accompanied by increased levels of endogenous itaconate, a metabolite produced by the IRG1 enzyme.
View Article and Find Full Text PDFUltrasound elastographic evaluation of renal parenchyma in pediatric patients with vesicoureteral reflux.
J Pediatr Urol
August 2025
Gaziantep University Medical Faculty, Department of Urology, Gaziantep, Turkey. Electronic address:
Objective: The most common chronic complication of vesicoureteral reflux (VUR) is the presence of renal scarring and dimercapto succinic acid (DMSA) renal scan is utilized for its detection. In this study, we have aimed to assess whether shear wave speed (SWS) differs between normal and refluxing kidneys.
Materials And Method: Fifty pediatric VUR patients and 21 healthy children with available DMSA obtained within the previous year were included in the study.