Role of glycolysis in inflammatory bowel disease and its associated colorectal cancer

Xia, Yuxuan; Zhang, Li; Ocansey, Dickson Kofi Wiredu; Tu, Qiang; Mao, Fei; Sheng, Xiumei

doi:10.3389/fendo.2023.1242991

Cited by 9 publications

(2 citation statements)

References 160 publications

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“…Other significant pathways identified by Kyoto Encyclopedia of Genes and Genomes analysis, such as glycolysis, are vital in IBD [ 64 ]. The energy and metabolites produced by glycolysis support the development and metabolism of bowel microbiota [ 65 ]. The glycolytic metabolic pathway regulates the immune system [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Yan,

Zhao,

Liu

et al. 2024

Renal Failure

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The mechanisms underlying the complex correlation between immunoglobulin A nephropathy (IgAN) and inflammatory bowel disease (IBD) remain unclear. This study aimed to identify the optimal cross-talk genes, potential pathways, and mutual immune-infiltrating microenvironments between IBD and IgAN to elucidate the linkage between patients with IBD and IgAN. The IgAN and IBD datasets were obtained from the Gene Expression Omnibus (GEO). Three algorithms, CIBERSORTx, ssGSEA, and xCell, were used to evaluate the similarities in the infiltrating microenvironment between the two diseases. Weighted gene co-expression network analysis (WGCNA) was implemented in the IBD dataset to identify the major immune infiltration modules, and the Boruta algorithm, RFE algorithm, and LASSO regression were applied to filter the cross-talk genes. Next, multiple machine learning models were applied to confirm the optimal cross-talk genes. Finally, the relevant findings were validated using histology and immunohistochemistry analysis of IBD mice. Immune infiltration analysis showed no significant differences between IBD and IgAN samples in most immune cells. The three algorithms identified 10 diagnostic genes, MAPK3, NFKB1, FDX1, EPHX2, SYNPO, KDF1, METTL7A, RIDA, HSDL2, and RIPK2; FDX1 and NFKB1 were enhanced in the kidney of IBD mice. Kyoto Encyclopedia of Genes and Genomes analysis showed 15 mutual pathways between the two diseases, with lipid metabolism playing a vital role in the cross-talk. Our findings offer insights into the shared immune mechanisms of IgAN and IBD. These common pathways, diagnostic cross-talk genes, and cell-mediated abnormal immunity may inform further experimental studies.

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Section: Discussionmentioning

confidence: 99%

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Yan,

Zhao,

Liu

et al. 2024

Renal Failure

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“…Glycolysis is a central anaerobic metabolic pathway producing energy for cell metabolism, and glycolysis is linked to the cellular inflammatory response to meet rapid energy demand upon inflammation [24,25]. We detected 22 proteins regulating glycolysis.…”

Section: Glycolysis Pathway Is Downregulated In Colon Of Colitismentioning

confidence: 99%

Colonic Dysregulation of Major Metabolic Pathways in Experimental Ulcerative Colitis

Noh,

Farhataziz,

Kinter

et al. 2024

Metabolites

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Inflammatory bowel disease (IBD) is multifactorial chronic inflammatory disease in the gastrointestinal tract, affecting patients’ quality of life profoundly. The incidence of IBD has been on the rise globally for the last two decades. Because the molecular mechanisms underlying the disease remain not well understood, therapeutic development is significantly impeded. Metabolism is a crucial cellular process to generate the energy needed for an inflammatory response and tissue repair. Comprehensive understanding of the metabolic pathways in IBD would help to unravel the disease pathogenesis/progression and facilitate therapeutic discoveries. Here, we investigated four metabolic pathways altered in experimental colitis. C57BL/6J mice were treated with dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental ulcerative colitis (UC). We conducted proteomics analysis for the colon samples using LC/MS, to profile key metabolic intermediates. Our findings revealed significant alterations in four major metabolic pathways: antioxidative defense, β-oxidation, glycolysis, and TCA cycle pathways. The energy metabolism by β-oxidation, glycolysis, and TCA cycle pathways were downregulated under UC, together with reduced antioxidative defense pathways. These results reveal metabolic re-programming in intestinal cells under UC, showing dysregulation in all four major metabolic pathways. Our study underscores the importance of metabolic drivers in the pathogenesis of IBD and suggests that the modification of metabolism may serve as a novel diagnostic/therapeutic approach for IBD.

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Tissue derivatization for visualizing lactate and pyruvate in mouse testis tissues using matrix-assisted laser desorption/ionization-mass spectrometry imaging

Nagano,

Odake,

Shimma

2024

Anal Bioanal Chem

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Pyruvate and lactate are the final metabolites of the glycolytic system that are formed under oxygen-rich and anaerobic conditions, respectively. They play an important role in energy metabolism. Obtaining a tissue distribution image of pyruvate and lactate holds great significance in molecular biology because the glycolytic system plays an essential role in diseases, such as tumors and diabetes; microbial activities, such as alcohol production and lactic acid fermentation; and maintaining homeostasis in the gut environment. However, it is difficult to obtain images of the distribution of in vivo metabolites because of the low detection sensitivities of current methods. In this study, a novel derivatization method for pyruvate and lactate was developed using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to detect pyruvate and lactate in vivo and obtain biodistribution images. We investigated derivatization methods using readily available 3-nitrophenylhydrazine (3NPH), the addition of which improves the sensitivity of pyruvate detection, and the distribution of pyruvate in mouse testes was successfully visualized. Furthermore, the distribution of lactate in the mouse testes could be visualized, and improved detection sensitivity for the main metabolites of the tricarboxylic acid cycle was demonstrated. This derivatization method can be used to detect carboxyl-containing metabolites, including pyruvate, via MALDI-MSI. Furthermore, 3NPH forms amide bonds with carbonyl, phosphate, and carboxyl groups, suggesting the possibility of visualizing its distribution in many metabolites. Graphical Abstract

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Role of glycolysis in inflammatory bowel disease and its associated colorectal cancer

Cited by 9 publications

References 160 publications

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Colonic Dysregulation of Major Metabolic Pathways in Experimental Ulcerative Colitis

Tissue derivatization for visualizing lactate and pyruvate in mouse testis tissues using matrix-assisted laser desorption/ionization-mass spectrometry imaging

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