Polyamines and Gut Microbiota

Tofalo, Rosanna; Cocchi, Simone; Suzzi, Giovanna

doi:10.3389/fnut.2019.00016

Cited by 191 publications

(135 citation statements)

References 56 publications

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“…In the examined cohort of patients, ODC1 was upregulated in the colon, more markedly in quiescent tissue, but not in the small bowel. ODC1 is a rate-limiting step in the synthesis of polyamines, which play important roles in both physiology and pathology regulating a number of cellular functions; among others, they induce proliferation and migration of intestinal epithelial cells, necessary for repair processes [16,17], but may also induce apoptosis or trigger neoplastic transformation [64,65]. ODC1 inhibition and subsequent polyamine depletion prevented TNFα-induced apoptosis in normal intestinal epithelial cells [16].…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Krzystek−Korpacka

Fleszar

Bednarz−Misa

et al. 2020

IJMS

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L-arginine/nitric oxide pathway in Crohn's disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 µM) compared to controls (157 and 0.494 µM) and active-UC (164 and 0.52 µM). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 µM) and active-UC (65.9 and 73.9 µM) compared to controls (42.7 and 50.4 µM). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted.

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Section: Discussionmentioning

confidence: 99%

“…Combination chemoprevention with ODC1 inhibitors has shown very promising results [13][14][15]. However, targeting ODC1 in IBD is controversial as polyamines are necessary for intestinal healing and gut health in general [16,17]. Modulating arginine availability has recently gained attention as well.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Krzystek−Korpacka

Fleszar

Bednarz−Misa

et al. 2020

IJMS

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“…[ 113 ] The main polyamines found in humans are spermine, spermidine, and putrescine, which may be derived from endogenous synthesis, diet, or the gut microbiota. [ 114 ] These polyamines are synthesized from two amino acids, ornithine or methionine, and are interconvertible to fulfill cellular physiological needs. [ 113 ] Polyamines have well‐established roles in cellular proliferation and differentiation, [ 115 ] and are known to regulate anti‐inflammatory responses, [ 116 ] reduce mutagenesis, [ 117 ] and, perhaps most interestingly, induce autophagy and promote longevity in flies and mice.…”

Section: Gut Microbial Metabolites and Intestinal Stem Cell Activitiesmentioning

confidence: 99%

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

2020

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Microorganisms that colonize the gastrointestinal tract, collectively known as the gut microbiota, are known to produce small molecules and metabolites that significantly contribute to host intestinal development, functions, and homeostasis. Emerging insights from microbiome research reveal that gut microbiota‐derived signals and molecules influence another key player maintaining intestinal homeostasis—the intestinal stem cell niche, which regulates epithelial self‐renewal. In this review, the literature on gut microbiota‐host crosstalk is surveyed, highlighting the effects of gut microbial metabolites on intestinal stem cells. The production of various classes of metabolites, their actions on intestinal stem cells are discussed and, finally, how the production and function of metabolites are modulated by aging and dietary intake is commented upon.

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“…Gut microbiota also synthesizes important compounds, such as methyl or acetyl groups, B vitamins, including riboflavin (B2), niacin (B3), biotin (B8), pantothenic acid (B5), and folate (B6), as well as various enzymes (methyltransferases, acetyltransferase, deacetylase, BirA ligase, phosphotransferases) that, as will be discussed later, play a role in DNA methylation and histone modifications, thus influencing all physiologic and pathologic processes in which epigenetic changes are fundamental [86]. It also synthesizes polyamines, low-molecular-weight aliphatic polycations, such as putrescine, spermidine, and spermine [87]. They are essential for the survival and virulence of several bacterial pathogens, such as Helicobacter pylori, Shigella spp, Staphylococcus aureus, and modulate systemic and mucosal adaptive immunity.…”

Section: Gut Microbiota Metabolitesmentioning

confidence: 99%

Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host

et al. 2020

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The human gut microbiota is a complex ecosystem consisting of trillions of microorganisms that inhabit symbiotically on and in the human intestine. They carry out, through the production of a series of metabolites, many important metabolic functions that complement the activity of mammalian enzymes and play an essential role in host digestion. Interindividual variability of microbiota structure, and consequently of the expression of its genes (microbiome), was largely ascribed to the nutritional regime. Diet influences microbiota composition and function with short- and long-term effects. In spite of the vast literature, molecular mechanisms underlying these effects still remain elusive. In this review, we summarized the current evidence on the role exerted by gut microbiota and, more specifically, by its metabolites in the establishment of the host epigenome. The interest in this topic stems from the fact that, by modulating DNA methylation and histone modifications, the gut microbiota does affect the cell activities of the hosting organism.

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Polyamines and Gut Microbiota

Cited by 191 publications

References 56 publications

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host

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