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

Accumulating evidence indicates that the gut microbiome and metabolites are associated with colorectal cancer (CRC). However, the influence of surgery for CRC treatment on the gut microbiome and metabolites and how it relates to CRC risk in postoperative CRC patients remain partially understood. Her...

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Autores principales: Shiroma, Hirotsugu, Shiba, Satoshi, Erawijantari, Pande Putu, Takamaru, Hiroyuki, Yamada, Masayoshi, Sakamoto, Taku, Kanemitsu, Yukihide, Mizutani, Sayaka, Soga, Tomoyoshi, Saito, Yutaka, Shibata, Tatsuhiro, Fukuda, Shinji, Yachida, Shinichi, Yamada, Takuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040882/
https://www.ncbi.nlm.nih.gov/pubmed/35311577
http://dx.doi.org/10.1128/msystems.00018-22
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author Shiroma, Hirotsugu
Shiba, Satoshi
Erawijantari, Pande Putu
Takamaru, Hiroyuki
Yamada, Masayoshi
Sakamoto, Taku
Kanemitsu, Yukihide
Mizutani, Sayaka
Soga, Tomoyoshi
Saito, Yutaka
Shibata, Tatsuhiro
Fukuda, Shinji
Yachida, Shinichi
Yamada, Takuji
author_facet Shiroma, Hirotsugu
Shiba, Satoshi
Erawijantari, Pande Putu
Takamaru, Hiroyuki
Yamada, Masayoshi
Sakamoto, Taku
Kanemitsu, Yukihide
Mizutani, Sayaka
Soga, Tomoyoshi
Saito, Yutaka
Shibata, Tatsuhiro
Fukuda, Shinji
Yachida, Shinichi
Yamada, Takuji
author_sort Shiroma, Hirotsugu
collection PubMed
description Accumulating evidence indicates that the gut microbiome and metabolites are associated with colorectal cancer (CRC). However, the influence of surgery for CRC treatment on the gut microbiome and metabolites and how it relates to CRC risk in postoperative CRC patients remain partially understood. Here, we collected 170 fecal samples from 85 CRC patients pre- and approximately 1 year postsurgery and performed shotgun metagenomic sequencing and capillary electrophoresis-time of flight mass spectrometry-based metabolomics analyses to characterize alterations between pre- and postsurgery. We determined that the relative abundance of 114 species was altered postsurgery (P < 0.005). CRC-associated species, such as Fusobacterium nucleatum, were decreased postsurgery. On the other hand, Clostridium scindens, carcinogenesis-associated deoxycholate (DCA)-producing species, and its biotransformed genes (bai operon) were increased postsurgery. The concentration of 60 fecal metabolites was also altered postsurgery (P < 0.005). Two bile acids, cholate and DCA, were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions using a random forest machine-learning algorithm that classifies large adenoma or early-stage CRC and healthy controls from publicly available data sets. We applied methods to preoperative samples and then compared the estimated CRC risk between the two groups according to the presence of large adenoma or tumors 5 years postsurgery (P < 0.05). Overall, our results show that the gut microbiome and metabolites dynamically change from pre- to postsurgery. In postoperative CRC patients, potential CRC risk derived from gut microbiome and metabolites still remains, which indicates the importance of follow-up assessments. IMPORTANCE The gut microbiome and metabolites are associated with CRC progression and carcinogenesis. Postoperative CRC patients are reported to be at an increased CRC risk; however, how gut microbiome and metabolites are related to CRC risk in postoperative patients remains only partially understood. In this study, we investigated the influence of surgical CRC treatment on the gut microbiome and metabolites. We found that the CRC-associated species Fusobacterium nucleatum was decreased postsurgery, whereas carcinogenesis-associated DCA and its producing species and genes were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions. We applied methods to compare the estimated CRC risk between two groups according to the presence of large adenoma or tumors after 5 years postsurgery. To our knowledge, this study is the first report on differences between pre- and postsurgery using metagenomics and metabolomics data analysis. Our methods might be used for CRC risk assessment in postoperative patients.
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spelling pubmed-90408822022-04-27 Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits Shiroma, Hirotsugu Shiba, Satoshi Erawijantari, Pande Putu Takamaru, Hiroyuki Yamada, Masayoshi Sakamoto, Taku Kanemitsu, Yukihide Mizutani, Sayaka Soga, Tomoyoshi Saito, Yutaka Shibata, Tatsuhiro Fukuda, Shinji Yachida, Shinichi Yamada, Takuji mSystems Research Article Accumulating evidence indicates that the gut microbiome and metabolites are associated with colorectal cancer (CRC). However, the influence of surgery for CRC treatment on the gut microbiome and metabolites and how it relates to CRC risk in postoperative CRC patients remain partially understood. Here, we collected 170 fecal samples from 85 CRC patients pre- and approximately 1 year postsurgery and performed shotgun metagenomic sequencing and capillary electrophoresis-time of flight mass spectrometry-based metabolomics analyses to characterize alterations between pre- and postsurgery. We determined that the relative abundance of 114 species was altered postsurgery (P < 0.005). CRC-associated species, such as Fusobacterium nucleatum, were decreased postsurgery. On the other hand, Clostridium scindens, carcinogenesis-associated deoxycholate (DCA)-producing species, and its biotransformed genes (bai operon) were increased postsurgery. The concentration of 60 fecal metabolites was also altered postsurgery (P < 0.005). Two bile acids, cholate and DCA, were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions using a random forest machine-learning algorithm that classifies large adenoma or early-stage CRC and healthy controls from publicly available data sets. We applied methods to preoperative samples and then compared the estimated CRC risk between the two groups according to the presence of large adenoma or tumors 5 years postsurgery (P < 0.05). Overall, our results show that the gut microbiome and metabolites dynamically change from pre- to postsurgery. In postoperative CRC patients, potential CRC risk derived from gut microbiome and metabolites still remains, which indicates the importance of follow-up assessments. IMPORTANCE The gut microbiome and metabolites are associated with CRC progression and carcinogenesis. Postoperative CRC patients are reported to be at an increased CRC risk; however, how gut microbiome and metabolites are related to CRC risk in postoperative patients remains only partially understood. In this study, we investigated the influence of surgical CRC treatment on the gut microbiome and metabolites. We found that the CRC-associated species Fusobacterium nucleatum was decreased postsurgery, whereas carcinogenesis-associated DCA and its producing species and genes were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions. We applied methods to compare the estimated CRC risk between two groups according to the presence of large adenoma or tumors after 5 years postsurgery. To our knowledge, this study is the first report on differences between pre- and postsurgery using metagenomics and metabolomics data analysis. Our methods might be used for CRC risk assessment in postoperative patients. American Society for Microbiology 2022-03-21 /pmc/articles/PMC9040882/ /pubmed/35311577 http://dx.doi.org/10.1128/msystems.00018-22 Text en Copyright © 2022 Shiroma et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Shiroma, Hirotsugu
Shiba, Satoshi
Erawijantari, Pande Putu
Takamaru, Hiroyuki
Yamada, Masayoshi
Sakamoto, Taku
Kanemitsu, Yukihide
Mizutani, Sayaka
Soga, Tomoyoshi
Saito, Yutaka
Shibata, Tatsuhiro
Fukuda, Shinji
Yachida, Shinichi
Yamada, Takuji
Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits
title Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits
title_full Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits
title_fullStr Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits
title_full_unstemmed Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits
title_short Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits
title_sort surgical treatment for colorectal cancer partially restores gut microbiome and metabolome traits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040882/
https://www.ncbi.nlm.nih.gov/pubmed/35311577
http://dx.doi.org/10.1128/msystems.00018-22
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