Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma
Background The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.Methods From November 2018...
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BMJ Publishing Group
2024-06-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/6/e008686.full |
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| author | Longhao Zhang Shanshan Wang Yajun Liang Xiaobo Yang Haitao Zhao Xinting Sang Dongya Zhang Zhou Lan Hanping Wang Ziyu Xun Chenchen Zhang Chengpei Zhu Jiashuo Chao Zilun Pu Cong Ning Xianzhi Jiang |
| author_facet | Longhao Zhang Shanshan Wang Yajun Liang Xiaobo Yang Haitao Zhao Xinting Sang Dongya Zhang Zhou Lan Hanping Wang Ziyu Xun Chenchen Zhang Chengpei Zhu Jiashuo Chao Zilun Pu Cong Ning Xianzhi Jiang |
| author_sort | Longhao Zhang |
| collection | DOAJ |
| description | Background The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.Methods From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC.Results Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6–8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI.Conclusions In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers. |
| format | Article |
| id | doaj-art-ecd15d05f5644e09b41e04765b556c13 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-ecd15d05f5644e09b41e04765b556c132025-08-20T03:07:06ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-06-0112610.1136/jitc-2023-008686Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinomaLonghao Zhang0Shanshan Wang1Yajun Liang2Xiaobo Yang3Haitao Zhao4Xinting Sang5Dongya Zhang6Zhou Lan7Hanping Wang8Ziyu Xun9Chenchen Zhang10Chengpei Zhu11Jiashuo Chao12Zilun Pu13Cong Ning14Xianzhi Jiang15Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaShanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP), Department of Environmental Science and Engineering, Fudan University, Shanghai, ChinaMicrobiome Research Center, Moon (Guangzhou) Biotech Ltd, Guangzhou, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaMicrobiome Research Center, Moon (Guangzhou) Biotech Ltd, Guangzhou, ChinaMicrobiome Research Center, Moon (Guangzhou) Biotech Ltd, Guangzhou, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaSchool of Nursing, Bengbu Medical College, Bengbu, Anhui, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaMicrobiome Research Center, Moon (Guangzhou) Biotech Ltd, Guangzhou, ChinaDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, ChinaAmberstone Biosciences, Irvine, CA, USABackground The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.Methods From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC.Results Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6–8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI.Conclusions In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers.https://jitc.bmj.com/content/12/6/e008686.full |
| spellingShingle | Longhao Zhang Shanshan Wang Yajun Liang Xiaobo Yang Haitao Zhao Xinting Sang Dongya Zhang Zhou Lan Hanping Wang Ziyu Xun Chenchen Zhang Chengpei Zhu Jiashuo Chao Zilun Pu Cong Ning Xianzhi Jiang Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma Journal for ImmunoTherapy of Cancer |
| title | Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma |
| title_full | Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma |
| title_fullStr | Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma |
| title_full_unstemmed | Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma |
| title_short | Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma |
| title_sort | characterizations of multi kingdom gut microbiota in immune checkpoint inhibitor treated hepatocellular carcinoma |
| url | https://jitc.bmj.com/content/12/6/e008686.full |
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