Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal Cancer

Abstract Immunotherapy has revolutionized the treatment of gastrointestinal (GI) cancers, but reliable biomarkers for predicting treatment efficacy remain limited. In this study, we explored the potential of blood microbiome and specific microbial taxa as novel biomarkers for predicting the efficacy...

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Main Authors: Ya‐Shang Zheng, Wu‐Hao Lin, Jun‐Quan Chen, Xiao‐Li Wei, Jia‐Qian Huang, Yu‐Hong Xu, Meng Yang, Qi‐Hua Zhang, Zhi‐Jun Zuo, Zhao‐Ying Yang, Pan Zhang, Nga Ki HONG, Lu‐Xuan Liu, Zhao‐Lei Zeng, Rui‐Hua Xu, Hui‐Yan Luo
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:MedComm
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Online Access:https://doi.org/10.1002/mco2.70316
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author Ya‐Shang Zheng
Wu‐Hao Lin
Jun‐Quan Chen
Xiao‐Li Wei
Jia‐Qian Huang
Yu‐Hong Xu
Meng Yang
Qi‐Hua Zhang
Zhi‐Jun Zuo
Zhao‐Ying Yang
Pan Zhang
Nga Ki HONG
Lu‐Xuan Liu
Zhao‐Lei Zeng
Rui‐Hua Xu
Hui‐Yan Luo
author_facet Ya‐Shang Zheng
Wu‐Hao Lin
Jun‐Quan Chen
Xiao‐Li Wei
Jia‐Qian Huang
Yu‐Hong Xu
Meng Yang
Qi‐Hua Zhang
Zhi‐Jun Zuo
Zhao‐Ying Yang
Pan Zhang
Nga Ki HONG
Lu‐Xuan Liu
Zhao‐Lei Zeng
Rui‐Hua Xu
Hui‐Yan Luo
author_sort Ya‐Shang Zheng
collection DOAJ
description Abstract Immunotherapy has revolutionized the treatment of gastrointestinal (GI) cancers, but reliable biomarkers for predicting treatment efficacy remain limited. In this study, we explored the potential of blood microbiome and specific microbial taxa as novel biomarkers for predicting the efficacy of immunotherapy combined with chemotherapy in GI cancer patients through 16S rRNA sequencing. Our findings demonstrated that lower baseline alpha diversity and specific microbial compositions, particularly lower levels of Lactobacillus, were significantly associated with longer progression‐free survival (PFS) in patients receiving immunotherapy combined with chemotherapy. Furthermore, we validated the reliability of Lactobacillus abundance as a predictor of PFS and treatment response in another independent patient cohort. Additionally, patients with increased or stable levels of Lactobacillus after immunotherapy combined with chemotherapy had superior PFS. Gavage of Lactobacillus rhamnosus (L. rhamnosus) el evated its blood level and enhanced the efficacy of immunotherapy in mouse models. Our results suggest that Lactobacillus may serve as a novel biomarker for predicting the efficacy of immunotherapy combined with chemotherapy and hold the potential as a PD‐1 antibody sensitizer.
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institution Kabale University
issn 2688-2663
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publishDate 2025-08-01
publisher Wiley
record_format Article
series MedComm
spelling doaj-art-9f06e89e7a754a7cb5fbc2ea6d7396be2025-08-20T03:43:34ZengWileyMedComm2688-26632025-08-0168n/an/a10.1002/mco2.70316Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal CancerYa‐Shang Zheng0Wu‐Hao Lin1Jun‐Quan Chen2Xiao‐Li Wei3Jia‐Qian Huang4Yu‐Hong Xu5Meng Yang6Qi‐Hua Zhang7Zhi‐Jun Zuo8Zhao‐Ying Yang9Pan Zhang10Nga Ki HONG11Lu‐Xuan Liu12Zhao‐Lei Zeng13Rui‐Hua Xu14Hui‐Yan Luo15Department of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Molecular Diagnostics State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Anesthesiology Sun Yat‐Sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaSun Yat‐Sen University Zhongshan School of Medicine Guangzhou People's Republic of ChinaSun Yat‐Sen University Zhongshan School of Medicine Guangzhou People's Republic of ChinaSun Yat‐Sen University Zhongshan School of Medicine Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of ChinaAbstract Immunotherapy has revolutionized the treatment of gastrointestinal (GI) cancers, but reliable biomarkers for predicting treatment efficacy remain limited. In this study, we explored the potential of blood microbiome and specific microbial taxa as novel biomarkers for predicting the efficacy of immunotherapy combined with chemotherapy in GI cancer patients through 16S rRNA sequencing. Our findings demonstrated that lower baseline alpha diversity and specific microbial compositions, particularly lower levels of Lactobacillus, were significantly associated with longer progression‐free survival (PFS) in patients receiving immunotherapy combined with chemotherapy. Furthermore, we validated the reliability of Lactobacillus abundance as a predictor of PFS and treatment response in another independent patient cohort. Additionally, patients with increased or stable levels of Lactobacillus after immunotherapy combined with chemotherapy had superior PFS. Gavage of Lactobacillus rhamnosus (L. rhamnosus) el evated its blood level and enhanced the efficacy of immunotherapy in mouse models. Our results suggest that Lactobacillus may serve as a novel biomarker for predicting the efficacy of immunotherapy combined with chemotherapy and hold the potential as a PD‐1 antibody sensitizer.https://doi.org/10.1002/mco2.70316biomarkerblood microbiomeefficacyimmunotherapyLactobacillus
spellingShingle Ya‐Shang Zheng
Wu‐Hao Lin
Jun‐Quan Chen
Xiao‐Li Wei
Jia‐Qian Huang
Yu‐Hong Xu
Meng Yang
Qi‐Hua Zhang
Zhi‐Jun Zuo
Zhao‐Ying Yang
Pan Zhang
Nga Ki HONG
Lu‐Xuan Liu
Zhao‐Lei Zeng
Rui‐Hua Xu
Hui‐Yan Luo
Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal Cancer
MedComm
biomarker
blood microbiome
efficacy
immunotherapy
Lactobacillus
title Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal Cancer
title_full Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal Cancer
title_fullStr Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal Cancer
title_full_unstemmed Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal Cancer
title_short Blood Microbiome Reveals the Impact of Lactobacillus on the Efficacy of Immunotherapy in Gastrointestinal Cancer
title_sort blood microbiome reveals the impact of lactobacillus on the efficacy of immunotherapy in gastrointestinal cancer
topic biomarker
blood microbiome
efficacy
immunotherapy
Lactobacillus
url https://doi.org/10.1002/mco2.70316
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