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Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer

Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the a...

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Autores principales: Huang, Jiayuan, Zheng, Xing, Kang, Wanying, Hao, Huaijie, Mao, Yudan, Zhang, Hua, Chen, Yuan, Tan, Yan, He, Yulong, Zhao, Wenjing, Yin, Yiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336524/
https://www.ncbi.nlm.nih.gov/pubmed/35911731
http://dx.doi.org/10.3389/fimmu.2022.874922
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author Huang, Jiayuan
Zheng, Xing
Kang, Wanying
Hao, Huaijie
Mao, Yudan
Zhang, Hua
Chen, Yuan
Tan, Yan
He, Yulong
Zhao, Wenjing
Yin, Yiming
author_facet Huang, Jiayuan
Zheng, Xing
Kang, Wanying
Hao, Huaijie
Mao, Yudan
Zhang, Hua
Chen, Yuan
Tan, Yan
He, Yulong
Zhao, Wenjing
Yin, Yiming
author_sort Huang, Jiayuan
collection PubMed
description Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies.
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spelling pubmed-93365242022-07-30 Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer Huang, Jiayuan Zheng, Xing Kang, Wanying Hao, Huaijie Mao, Yudan Zhang, Hua Chen, Yuan Tan, Yan He, Yulong Zhao, Wenjing Yin, Yiming Front Immunol Immunology Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies. Frontiers Media S.A. 2022-07-15 /pmc/articles/PMC9336524/ /pubmed/35911731 http://dx.doi.org/10.3389/fimmu.2022.874922 Text en Copyright © 2022 Huang, Zheng, Kang, Hao, Mao, Zhang, Chen, Tan, He, Zhao and Yin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Huang, Jiayuan
Zheng, Xing
Kang, Wanying
Hao, Huaijie
Mao, Yudan
Zhang, Hua
Chen, Yuan
Tan, Yan
He, Yulong
Zhao, Wenjing
Yin, Yiming
Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer
title Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer
title_full Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer
title_fullStr Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer
title_full_unstemmed Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer
title_short Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer
title_sort metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-pd-1 therapy on treating colorectal cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336524/
https://www.ncbi.nlm.nih.gov/pubmed/35911731
http://dx.doi.org/10.3389/fimmu.2022.874922
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