Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study
Abstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. P...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-09-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-023-01515-3 |
| _version_ | 1827632963595010048 |
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| author | Junqi Wu Chongwu Li Peigen Gao Chenhong Zhang Pei Zhang Lei Zhang Chenyang Dai Kunpeng Zhang Bowen Shi Mengyang Liu Junmeng Zheng Bo Pan Zhan Chen Chao Zhang Wanqing Liao Weihua Pan Wenjie Fang Chang Chen |
| author_facet | Junqi Wu Chongwu Li Peigen Gao Chenhong Zhang Pei Zhang Lei Zhang Chenyang Dai Kunpeng Zhang Bowen Shi Mengyang Liu Junmeng Zheng Bo Pan Zhan Chen Chao Zhang Wanqing Liao Weihua Pan Wenjie Fang Chang Chen |
| author_sort | Junqi Wu |
| collection | DOAJ |
| description | Abstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs. |
| first_indexed | 2024-03-09T14:51:56Z |
| format | Article |
| id | doaj.art-1811a7093f304bb5b94eadcea3acfc2e |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-03-09T14:51:56Z |
| publishDate | 2023-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-1811a7093f304bb5b94eadcea3acfc2e2023-11-26T14:22:12ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352023-09-01811910.1038/s41392-023-01515-3Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort studyJunqi Wu0Chongwu Li1Peigen Gao2Chenhong Zhang3Pei Zhang4Lei Zhang5Chenyang Dai6Kunpeng Zhang7Bowen Shi8Mengyang Liu9Junmeng Zheng10Bo Pan11Zhan Chen12Chao Zhang13Wanqing Liao14Weihua Pan15Wenjie Fang16Chang Chen17Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Changhai Hospital, Naval Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Dermatology, Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Naval Medical UniversityAdfontes (Shanghai) Bio-technology Co., LtdDepartment of Dermatology, Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Naval Medical UniversityDepartment of Dermatology, Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Naval Medical UniversityDepartment of Dermatology, Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Naval Medical UniversityDepartment of Dermatology, Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Naval Medical UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityAbstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.https://doi.org/10.1038/s41392-023-01515-3 |
| spellingShingle | Junqi Wu Chongwu Li Peigen Gao Chenhong Zhang Pei Zhang Lei Zhang Chenyang Dai Kunpeng Zhang Bowen Shi Mengyang Liu Junmeng Zheng Bo Pan Zhan Chen Chao Zhang Wanqing Liao Weihua Pan Wenjie Fang Chang Chen Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study Signal Transduction and Targeted Therapy |
| title | Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study |
| title_full | Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study |
| title_fullStr | Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study |
| title_full_unstemmed | Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study |
| title_short | Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study |
| title_sort | intestinal microbiota links to allograft stability after lung transplantation a prospective cohort study |
| url | https://doi.org/10.1038/s41392-023-01515-3 |
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