Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Soda, Kuniyasu

doi:10.3390/ijms19103106

Cited by 64 publications

(51 citation statements)

References 356 publications

(397 reference statements)

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“…It has also been established that Arg may improve the migration of epithelial cells, increase villus height and crypt depth, and decrease cell apoptosis in methotrexate (MTX)-induced mucositis and DSS colitis 35 . Long-term increased polyamine (L-Orn metabolites) intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans 36 . Since L-Orn from lactobacillus through Arg metabolism may promote gut mucus homeostasis, our results expand understanding of the mechanism by which Arg contributes to this homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus maintains healthy gut mucosa by producing L-Ornithine

Yun

et al. 2019

Commun Biol

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Gut mucosal layers are crucial in maintaining the gut barrier function. Gut microbiota regulate homeostasis of gut mucosal layer via gut immune cells such as RORγt (+) IL-22(+) ILC3 cells, which can influence the proliferation of mucosal cells and the production of mucin. However, it is unclear how gut microbiota execute this regulation. Here we show that lactobacilli promote gut mucosal formation by producing L-Ornithine from arginine. L-Ornithine increases the level of aryl hydrocarbon receptor ligand L-kynurenine produced from tryptophan metabolism in gut epithelial cells, which in turn increases RORγt (+)IL-22(+) ILC3 cells. Human REG3A transgenic mice show an increased proportion of L-Ornithine producing lactobacilli in the gut contents, suggesting that gut epithelial REG3A favors the expansion of L-Ornithine producing lactobacilli. Our study implicates the importance of a crosstalk between arginine metabolism in Lactobacilli and tryptophan metabolism in gut epithelial cells in maintaining gut barrier.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus maintains healthy gut mucosa by producing L-Ornithine

Yun

et al. 2019

Commun Biol

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“…Maintaining flux through this cycle is critical for two reasons. First, circumstantial evidence suggests that dcSAM inhibits DNA methyl transferases [23], and perhaps other methyltransferases. Second, MTA is a competitive inhibitor of protein arginine N-methyltransferase 5 (PRMT5) [24].…”

Section: Polyamine Synthesis and Methionine Metabolismmentioning

confidence: 99%

Methionine Dependence of Cancer

2020

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Tumorigenesis is accompanied by the reprogramming of cellular metabolism. The shift from oxidative phosphorylation to predominantly glycolytic pathways to support rapid growth is well known and is often referred to as the Warburg effect. However, other metabolic changes and acquired needs that distinguish cancer cells from normal cells have also been discovered. The dependence of cancer cells on exogenous methionine is one of them and is known as methionine dependence or the Hoffman effect. This phenomenon describes the inability of cancer cells to proliferate when methionine is replaced with its metabolic precursor, homocysteine, while proliferation of non-tumor cells is unaffected by these conditions. Surprisingly, cancer cells can readily synthesize methionine from homocysteine, so their dependency on exogenous methionine reflects a general need for altered metabolic flux through pathways linked to methionine. In this review, an overview of the field will be provided and recent discoveries will be discussed.

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“…In addition to SCFAs, other metabolites produced by the bacteria from the gastrointestinal tract have been related to epigenetic modifications (Bhat and Kapila, 2017). In particular, gut bacteria can produce high levels of folic acid and polyamines, which are molecules highly related to carbon metabolism and therefore with potential impact in the DNA methylation status (Crider et al, 2012; Soda, 2018; Ramos-Molina et al, 2019). Nevertheless, whether the changes in the methylome associated with alterations in gut microbiome are related to changes in the levels of these or other bacterial metabolites requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, the existence of a crosstalk between the gut microbiome and the epigenome has been suggested (Qin and Wade, 2018). It has been proposed that certain metabolites generated by the gut microbiota such as short-chain fatty acids (SCFAs), folate, and polyamines can act as epigenetic modulators by affecting DNA methylation and inducing histone modifications (Crider et al, 2012; Paul et al, 2015; Bhat and Kapila, 2017; Soda, 2018; Cuevas-Sierra et al, 2019; Ramos-Molina et al, 2019). However, the possible link between alterations in gut microbiome composition and epigenetic marks in the context of obesity has been not explored yet.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Composition Is Associated With the Global DNA Methylation Pattern in Obesity

Ramos‐Molina¹,

Sánchez-Alcoholado²,

Cabrera-Mulero³

et al. 2019

Front. Genet.

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Objective: Obesity and obesity-related metabolic diseases are characterized by gut microbiota and epigenetic alterations. Recent insight has suggested the existence of a crosstalk between the gut microbiome and the epigenome. However, the possible link between alterations in gut microbiome composition and epigenetic marks in obesity has been not explored yet. The aim of this work is to establish a link between the gut microbiota and the global DNA methylation profile in a group of obese subjects and to report potential candidate genes that could be epigenetically regulated by gut microbiota in adipose tissue. Methods: Gut microbiota composition was analyzed in DNA stool samples from 45 obese subjects by 16S ribosomal RNA (rRNA) gene sequencing. Twenty patients were selected based on their Bacteroidetes-to-Firmicutes ratio (BFR): HighBFR group (BFR > 2.5, n = 10) and LowBFR group (BFR < 1.2, n = 10). Genome-wide analysis of DNA methylation pattern in both whole blood and visceral adipose tissue of these selected patients was performed with an Infinium EPIC BeadChip array-based platform. Gene expression analysis of candidate genes was done in adipose tissue by real-time quantitative PCR. Results: Genome-wide analysis of DNA methylation revealed a completely different DNA methylome pattern in both blood and adipose tissue in the low BFR group vs. the high BFR group. Two hundred fifty-eight genes were differentially methylated in both blood and adipose tissue, of which several potential candidates were selected for gene expression analysis. We found that in adipose tissue, both HDAC7 and IGF2BP2 were hypomethylated and overexpressed in the low BFR group compared with the high BFR group. β values of both genes significantly correlated with the BFR ratio and the relative abundance of Bacteroidetes and/or Firmicutes. Conclusions: In this study, we demonstrate that the DNA methylation status is associated with gut microbiota composition in obese subjects and that the expression levels of candidate genes implicated in glucose and energy homeostasis (e.g., HDAC7 and IGF2BP2 ) could be epigenetically regulated by gut bacterial populations in adipose tissue.

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Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Cited by 64 publications

References 356 publications

Lactobacillus maintains healthy gut mucosa by producing L-Ornithine

Lactobacillus maintains healthy gut mucosa by producing L-Ornithine

Methionine Dependence of Cancer

Gut Microbiota Composition Is Associated With the Global DNA Methylation Pattern in Obesity

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