The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study
Responses to neoadjuvant chemoradiotherapy (nCRT) and therapy-related toxicities in rectal cancer vary among patients. To provide the individualized therapeutic option for each patient, predictive markers of therapeutic responses and toxicities are in critical need. We aimed to identify the associat...
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Frontiers Media S.A.
2020-12-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2020.562463/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Shi Wei Shi Lijun Shen Lijun Shen Wei Zou Wei Zou Jingwen Wang Jingwen Wang Jianing Yang Jianing Yang Yuezhu Wang Bingdong Liu Liwei Xie Liwei Xie Liwei Xie Ji Zhu Ji Zhu Zhen Zhang Zhen Zhang |
spellingShingle |
Wei Shi Wei Shi Lijun Shen Lijun Shen Wei Zou Wei Zou Jingwen Wang Jingwen Wang Jianing Yang Jianing Yang Yuezhu Wang Bingdong Liu Liwei Xie Liwei Xie Liwei Xie Ji Zhu Ji Zhu Zhen Zhang Zhen Zhang The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study Frontiers in Cellular and Infection Microbiology gut microbiome rectal cancer neoadjuvant chemoradiotherapy therapeutic responses toxicities |
author_facet |
Wei Shi Wei Shi Lijun Shen Lijun Shen Wei Zou Wei Zou Jingwen Wang Jingwen Wang Jianing Yang Jianing Yang Yuezhu Wang Bingdong Liu Liwei Xie Liwei Xie Liwei Xie Ji Zhu Ji Zhu Zhen Zhang Zhen Zhang |
author_sort |
Wei Shi |
title |
The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study |
title_short |
The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study |
title_full |
The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study |
title_fullStr |
The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study |
title_full_unstemmed |
The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot Study |
title_sort |
gut microbiome is associated with therapeutic responses and toxicities of neoadjuvant chemoradiotherapy in rectal cancer patients—a pilot study |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2020-12-01 |
description |
Responses to neoadjuvant chemoradiotherapy (nCRT) and therapy-related toxicities in rectal cancer vary among patients. To provide the individualized therapeutic option for each patient, predictive markers of therapeutic responses and toxicities are in critical need. We aimed to identify the association of gut microbiome with and its potential predictive value for therapeutic responses and toxicities. In the present study, we collected fecal microbiome samples from patients with rectal cancer at treatment initiation and just after nCRT. Taxonomic profiling via 16S ribosomal RNA gene sequencing was performed on all samples. Patients were classified as responders versus non-responders. Patients were grouped into no or mild diarrhea and severe diarrhea. STAMP and high-dimensional class comparisons via linear discriminant analysis of effect size (LEfSe) were used to compare the compositional differences between groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was utilized to predict differences in metabolic function between groups. Ten patients were classified as responders and 12 patients were classified as non-responders. Fourteen patients experienced no or mild diarrhea and 8 patients experienced severe diarrhea. Several bacteria taxa with significantly different relative abundances before and after nCRT were identified. Similarly, several baseline bacteria taxa and predicted pathways with significantly different relative abundances between responders and non-responders or between patients no or mild diarrhea and severe diarrhea were identified. Specifically, Shuttleworthia was identified as enriched in responders and several bacteria taxa in the Clostridiales order etc. were identified as enriched in non-responders. Pathways including fatty acid metabolism were predicted to be enriched in responders. In addition, Bifidobacterium, Clostridia, and Bacteroides etc. were identified as enriched in patients with no or mild diarrhea. Pathways including primary bile acid biosynthesis were predicted to be enriched in patients with no or mild diarrhea. Together, the microbiota and pathway markers identified in this study may be utilized to predict the therapeutic responses and therapy-related toxicities of nCRT in patients with rectal cancer. More patient data is needed to verify the current findings and the results of metagenomic, metatranscriptomic, and metabolomic analyses will further mine key biomarkers at the compositional and functional level. |
topic |
gut microbiome rectal cancer neoadjuvant chemoradiotherapy therapeutic responses toxicities |
url |
https://www.frontiersin.org/articles/10.3389/fcimb.2020.562463/full |
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doaj-3ccb9d43270e4347b455f428031a404f2020-12-09T06:11:03ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-12-011010.3389/fcimb.2020.562463562463The Gut Microbiome Is Associated With Therapeutic Responses and Toxicities of Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients—A Pilot StudyWei Shi0Wei Shi1Lijun Shen2Lijun Shen3Wei Zou4Wei Zou5Jingwen Wang6Jingwen Wang7Jianing Yang8Jianing Yang9Yuezhu Wang10Bingdong Liu11Liwei Xie12Liwei Xie13Liwei Xie14Ji Zhu15Ji Zhu16Zhen Zhang17Zhen Zhang18Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Shanghai, ChinaSequencing Department, Chinese National Human Genome Center at Shanghai, Shanghai, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, ChinaZhujiang Hospital, Southern Medical University, Guangzhou, ChinaSchool of Public Health, Xinxiang Medical College, Xinxiang, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Shanghai, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Shanghai, ChinaResponses to neoadjuvant chemoradiotherapy (nCRT) and therapy-related toxicities in rectal cancer vary among patients. To provide the individualized therapeutic option for each patient, predictive markers of therapeutic responses and toxicities are in critical need. We aimed to identify the association of gut microbiome with and its potential predictive value for therapeutic responses and toxicities. In the present study, we collected fecal microbiome samples from patients with rectal cancer at treatment initiation and just after nCRT. Taxonomic profiling via 16S ribosomal RNA gene sequencing was performed on all samples. Patients were classified as responders versus non-responders. Patients were grouped into no or mild diarrhea and severe diarrhea. STAMP and high-dimensional class comparisons via linear discriminant analysis of effect size (LEfSe) were used to compare the compositional differences between groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was utilized to predict differences in metabolic function between groups. Ten patients were classified as responders and 12 patients were classified as non-responders. Fourteen patients experienced no or mild diarrhea and 8 patients experienced severe diarrhea. Several bacteria taxa with significantly different relative abundances before and after nCRT were identified. Similarly, several baseline bacteria taxa and predicted pathways with significantly different relative abundances between responders and non-responders or between patients no or mild diarrhea and severe diarrhea were identified. Specifically, Shuttleworthia was identified as enriched in responders and several bacteria taxa in the Clostridiales order etc. were identified as enriched in non-responders. Pathways including fatty acid metabolism were predicted to be enriched in responders. In addition, Bifidobacterium, Clostridia, and Bacteroides etc. were identified as enriched in patients with no or mild diarrhea. Pathways including primary bile acid biosynthesis were predicted to be enriched in patients with no or mild diarrhea. Together, the microbiota and pathway markers identified in this study may be utilized to predict the therapeutic responses and therapy-related toxicities of nCRT in patients with rectal cancer. More patient data is needed to verify the current findings and the results of metagenomic, metatranscriptomic, and metabolomic analyses will further mine key biomarkers at the compositional and functional level.https://www.frontiersin.org/articles/10.3389/fcimb.2020.562463/fullgut microbiomerectal cancerneoadjuvant chemoradiotherapytherapeutic responsestoxicities |