Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine

Ohshima, Kenji; Nojima, Satoshi; Tahara, Shinichiro; Kurashige, Masako; Kawasaki, Koichiro; Hori, Yumiko; Taniguchi, Moyu; Umakoshi, Yutaka; Okuzaki, Daisuke; Wada, Naoki; Ikeda, Jun‐ichiro; Fukusaki, Eiichiro; Morii, Eiichi

doi:10.1038/s42255-019-0156-2

Cited by 29 publications

(28 citation statements)

References 42 publications

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“…The serine racemase enzyme produces pyruvate from serine. The role of this enzyme in CRC becomes more prominent with the production of pyruvate, and it aids tumor growth and is being investigated as a drug target [ 55 ]. Interestingly, our models confirmed these findings: firstly, its gene is present in Firmicutes, Actinobacteria and Fusobacteria, which are present and prevalent in CRC microbiota models.…”

Section: Discussionmentioning

confidence: 99%

A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression

et al. 2021

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The human gut microbiota plays a dual key role in maintaining human health or inducing disorders, for example, obesity, type 2 diabetes, and cancers such as colorectal cancer (CRC). High-throughput data analysis, such as metagenomics and metabolomics, have shown the diverse effects of alterations in dynamic bacterial populations on the initiation and progression of colorectal cancer. However, it is well established that microbiome and human cells constantly influence each other, so it is not appropriate to study them independently. Genome-scale metabolic modeling is a well-established mathematical framework that describes the dynamic behavior of these two axes at the system level. In this study, we created community microbiome models of three conditions during colorectal cancer progression, including carcinoma, adenoma and health status, and showed how changes in the microbial population influence intestinal secretions. Conclusively, our findings showed that alterations in the gut microbiome might provoke mutations and transform adenomas into carcinomas. These alterations include the secretion of mutagenic metabolites such as H2S, NO compounds, spermidine and TMA, as well as the reduction of butyrate. Furthermore, we found that the colorectal cancer microbiome can promote inflammation, cancer progression (e.g., angiogenesis) and cancer prevention (e.g., apoptosis) by increasing and decreasing certain metabolites such as histamine, glutamine and pyruvate. Thus, modulating the gut microbiome could be a promising strategy for the prevention and treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression

et al. 2021

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“…Previous studies demonstrated that F. nucleatum, a protumorigenic bacterium [32], could potentiate CRC cells [31]. In addition, serine is an energy resource for the production of pyruvate in CRC tissue, which plays a role in CRC cell growth [33]. The species and metabolites that were decreased in postsurgical status, which were elevated in advanced-stage CRC, may re ect the improvement in cancerous intestinal conditions in postoperative patients.…”

Section: Discussionmentioning

confidence: 99%

Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits

Shiroma¹,

Shiba²,

Erawijantari³

et al. 2021

Preprint

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Background: Postoperative colorectal cancer (CRC) patients are at increased risk of developing metachronous CRC. Despite accumulating evidence indicating that the gut microbiota and metabolites can promote CRC carcinogenesis, the influence of surgery for CRC on the gut microbiota and metabolites remains partially understood. We hypothesized that if surgery does not eliminate the bacteria and metabolites promoting CRC carcinogenesis, these bacteria and metabolites might be associated with the development of metachronous CRC. To test this hypothesis, we collected 170 fecal samples from 85 CRC patients in pre- and approximately one year postsurgery status, and performed shotgun metagenomics sequencing and capillary electrophoresis time-of-flight mass spectrometry-based metabolomics analyses and compared pre- and postsurgery status.Results: CRC-associated bacteria such as Parvimonas micra and Fusobacterium nucleatum were significantly (P < 0.005) decreased after surgery. On the other hand, cholate, carcinogenesis-associated deoxycholate, its biotransformed genes (bai operon) from cholate to deoxycholate, and the contributing bacterium (Clostridium scindens) were significantly (P < 0.005) increased. Additionally, these alterations were only observed in postleft surgery. Cholate and glycocholate were significantly (P < 0.005) increased in postright surgery. We also developed a method for potential CRC risk assessment based on the gut microbiota and metabolomic compositions using a random forest machine learning algorithm and then applied it to postoperative patients. The estimated CRC risk based on the random forest algorithm was partially restored postsurgery. Conclusions: Our results indicate that the high potential CRC risk in CRC postoperative patients is associated with metabolites derived from the gut microbiota, which targets interventions to reduce the CRC risk.

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“…Previous studies demonstrated that F. nucleatum , a protumorigenic bacterium ( 33 ), could potentiate CRC cells ( 8 ). In addition, serine is an energy resource for the production of pyruvate in CRC tissue, which plays a role in CRC cell growth ( 34 ). The species and metabolites that were decreased postsurgery, which were elevated in advanced-stage CRC, may reflect the improvement in cancerous intestinal conditions in postoperative patients.…”

Section: Discussionmentioning

confidence: 99%

Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits

Shiroma

Shiba²,

Erawijantari

et al. 2022

mSystems

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Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine

Cited by 29 publications

References 42 publications

A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression

A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression

Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits

Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits

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