Imidazole propionate is an early biomarker and therapeutic target for atherosclerosis [bulk RNA-seq]
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PROVIDER: PRJNA1266247 | ENA |
REPOSITORIES: ENA
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Project description:Atherosclerosis is the main underlying cause of cardiovascular diseases (CVDs). Its prevention is based on traditional cardiovascular risk factor-based scores but often fails to identify individuals at early stages of the disease. Here, we identified microbially produced imidazole propionate (ImP) as an early biomarker of atherosclerosis in mice and in two independent human cohorts. Furthermore, ImP administration induced atherosclerosis without altering lipid metabolism and it was associated with activation of both systemic and local innate and adaptive immunity and inflammation. Notably, ImP caused atherosclerosis through the Imidazoline-1 receptor (I1R), and the blockade of the ImP/I1R axis inhibited the development of atherosclerosis induced by ImP as well as by high cholesterol diet in mice. Here, we profiled three cell lines which represent cell types typically found in aortas (bone marrow-derived macrophages, mouse embryonic fibroblasts and mouse aortic endothelial cells) upon in vitro stimulation with ImP at different time points to better understand the transcriptional regulation of the ImP/I1R axis and its role in the development of the disease. Identification of ImP as an early biomarker for atherosclerosis and uncovering the contribution of the ImP/I1R axis in disease progression open new avenues to improve atherosclerosis early diagnosis and therapy.
2025-07-16 | GSE297831 | GEO
Project description:Atherosclerosis is the main underlying cause of cardiovascular diseases (CVDs). Its prevention is based on traditional cardiovascular risk factor-based scores but often fails to identify individuals at early stages of the disease. Here, we identified microbially produced imidazole propionate (ImP) as an early biomarker of atherosclerosis in mice and in two independent human cohorts. Furthermore, ImP administration induced atherosclerosis without altering lipid metabolism and it was associated with activation of both systemic and local innate and adaptive immunity and inflammation. Here, we used single-cell RNA-seq to characterize the local changes of aorta-derived cells in mice under treatment with ImP for 4 and 8 weeks. Notably, ImP caused atherosclerosis through the Imidazoline-1 receptor (I1R), and the blockade of the ImP/I1R axis inhibited the development of atherosclerosis induced by ImP as well as by high cholesterol diet in mice. Identification of ImP as an early biomarker for atherosclerosis and uncovering the contribution of the ImP/I1R axis in disease progression open new avenues to improve atherosclerosis early diagnosis and therapy.
2025-07-16 | GSE298392 | GEO
Project description:Imidazole propionate is a driver and therapeutic target in atherosclerosis [scRNA-seq]
| PRJNA1269065 | ENA
Project description:Imidazole propionate (ImP): effect on human aortic endothelial cells
| PRJEB61803 | ENA
Project description:Neural circuits driving mammalian behaviors are highly plastic and modulated by internal and external factors, including the gut microbiome. We identify imidazole propionate (ImP), a microbial metabolite linked to metabolic disorders, as a key modulator of brain activity and behavior. Bacterially derived ImP enters the systemic circulation and brain, where it alters neuronal gene expression and activity in the hypothalamus without inducing overt neuroinflammation. Elevating systemic ImP promotes stress-related pathways and disrupts GABAergic/glutamatergic signaling in the hypothalamus before peripheral glucose dysregulation occurs. Similarly, colonization with the ImP-producing bacterium Eggerthella lenta elevates behavioral and molecular features of stress. In a mouse model of type 2 diabetes, the gut microbiome exhibits an enhanced ability to produce ImP, leading to elevated systemic levels that are associated with heightened stress responses. In humans, higher ImP associates with reduced hypothalamic reactivity to food cues, impaired stress-coping, and increased emotional eating, mirroring the causal links between ImP, hypothalamic activity, and stress-related behaviors in mice. Overall, these findings establish ImP as a notable microbial metabolite that links gut dysbiosis to altered hypothalamic function and stress in metabolic disease.
2025-06-26 | GSE300937 | GEO
Project description:The microbial metabolite imidazole propionate modulates hypothalamic activity and stress-induced behaviors
| PRJNA1282701 | ENA
Project description:The alteration of metabolic pathways is a critical strategy for cancer cells to attain the traits necessary for metastasis in disease progression. We found that dysregulation of propionate metabolism occurs through TGFbeta- and ERK2-driven downregulation of methylmalonyl-CoA epimerase (MCEE). MCEE downregulation occurs through a transcription factor Sp1/EGR1 switch at its promoter region, resulting in reduced flux through this anapleurotic pathway and leading to accumulation of methylmalonic acid (MMA), a byproduct of the propionate metabolism. MMA accumulation through alteration of propionate metabolism produces a pro-aggressive signature in breast and lung cancer cells and increases their metastatic potential. Altogether, we present a previously uncharacterized dysregulation of propionate metabolism as a novel contributor to cancer and a valuable potential target in the therapeutic treatment of metastatic carcinomas.
2022-01-28 | GSE161108 | GEO
Project description:Background & aimsCirculating levels of imidazole propionate (ImP), a microbial metabolite of histidine, were higher in participants with type 2 diabetes (T2D) compared to those without and also induced insulin resistance. We hypothesize that low intake of magnesium (Mg) and/or low body Mg status in humans may lead to low Mg concentrations in gut microbiota, and, in turn, elevated microbial production of ImP and increased levels of circulating ImP.MethodsWe tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169), a double-blind 2 × 2 factorial randomized controlled trial enrolling 240 participants at high risk of Mg deficiency. Among 68 participants (34 each in the treatment and placebo arms), we measured plasma metabolites using the untargeted Metabolon's global Precision Metabolomics™ LC-MS platform.ResultsMg treatment significantly reduced ImP by 39.9% compared to a 6.0% increase in the placebo arm (P = 0.02). We found the correlation coefficients were -0.12 (P = 0.32) and -0.31 (P < 0.01) between the change in ImP and changes in serum Mg and urinary Mg, respectively. In addition, we found Mg treatment increased circulating levels of propionic acid (InP) by 27.5% (P = 0.07) and reduced levels of glutarate by 17.9% (P = 0.04) compared to the placebo arm.ConclusionsFurther studies are needed to replicate these findings and to investigate whether Mg treatment specifically changes the production of ImP by microbiota. Also, future studies are warranted to confirm the effect of Mg treatment on glutarate and InP.
| S-EPMC7835418 | biostudies-literature
Project description:Extracellular microRNA: Novel Biomarker and Potential Therapeutic Target in Trauma
| PRJNA925146 | ENA
Project description:Background: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. Methods: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. Results: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. Conclusions: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.
2024-05-02 | GSE221506 | GEO