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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.874922/full |
| _version_ | 1828543804873900032 |
|---|---|
| author | Jiayuan Huang Xing Zheng Wanying Kang Huaijie Hao Yudan Mao Hua Zhang Yuan Chen Yan Tan Yulong He Yulong He Wenjing Zhao Yiming Yin |
| author_facet | Jiayuan Huang Xing Zheng Wanying Kang Huaijie Hao Yudan Mao Hua Zhang Yuan Chen Yan Tan Yulong He Yulong He Wenjing Zhao Yiming Yin |
| author_sort | Jiayuan Huang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T02:20:10Z |
| format | Article |
| id | doaj.art-3f7630de986148c28eeddbafd31ea7c2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T02:20:10Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3f7630de986148c28eeddbafd31ea7c22022-12-22T00:41:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.874922874922Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancerJiayuan Huang0Xing Zheng1Wanying Kang2Huaijie Hao3Yudan Mao4Hua Zhang5Yuan Chen6Yan Tan7Yulong He8Yulong He9Wenjing Zhao10Yiming Yin11School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaDepartment of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaDepartment of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaDepartment of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaDepartment of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, ChinaAnti-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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.874922/fullfecal microbiota transplantationanti-PD-1 therapyimmunotherapycolorectal cancerBacteroides |
| spellingShingle | Jiayuan Huang Xing Zheng Wanying Kang Huaijie Hao Yudan Mao Hua Zhang Yuan Chen Yan Tan Yulong He Yulong He Wenjing Zhao Yiming Yin Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer Frontiers in Immunology fecal microbiota transplantation anti-PD-1 therapy immunotherapy colorectal cancer Bacteroides |
| 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 | fecal microbiota transplantation anti-PD-1 therapy immunotherapy colorectal cancer Bacteroides |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.874922/full |
| work_keys_str_mv | AT jiayuanhuang metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT xingzheng metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT wanyingkang metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT huaijiehao metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT yudanmao metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT huazhang metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT yuanchen metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT yantan metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT yulonghe metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT yulonghe metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT wenjingzhao metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer AT yimingyin metagenomicandmetabolomicanalysesrevealsynergisticeffectsoffecalmicrobiotatransplantationandantipd1therapyontreatingcolorectalcancer |