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Article

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

1
Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord 8818634141, Iran
2
Biotechnology Research Institute, Shahrekord University, Shahrekord 8818634141, Iran
3
Hematology, Oncology and SCT Research Center, Tehran University of Medical Sciences, Tehran 14114, Iran
4
Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Yiorgos Apidianakis and Agapios Agapiou
Metabolites 2021, 11(7), 456; https://doi.org/10.3390/metabo11070456
Received: 2 July 2021 / Revised: 12 July 2021 / Accepted: 13 July 2021 / Published: 15 July 2021
(This article belongs to the Special Issue Host-Microbe-Metabolite Interaction in Intestinal Health)
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 (trimethylamine), 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. View Full-Text
Keywords: microbiome; genome-scale metabolic model; community metabolic modeling; colorectal cancer microbiome; genome-scale metabolic model; community metabolic modeling; colorectal cancer
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MDPI and ACS Style

Salahshouri, P.; Emadi-Baygi, M.; Jalili, M.; Khan, F.M.; Wolkenhauer, O.; Salehzadeh-Yazdi, A. A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression. Metabolites 2021, 11, 456. https://doi.org/10.3390/metabo11070456

AMA Style

Salahshouri P, Emadi-Baygi M, Jalili M, Khan FM, Wolkenhauer O, Salehzadeh-Yazdi A. A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression. Metabolites. 2021; 11(7):456. https://doi.org/10.3390/metabo11070456

Chicago/Turabian Style

Salahshouri, Pejman, Modjtaba Emadi-Baygi, Mahdi Jalili, Faiz M. Khan, Olaf Wolkenhauer, and Ali Salehzadeh-Yazdi. 2021. "A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression" Metabolites 11, no. 7: 456. https://doi.org/10.3390/metabo11070456

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