Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation
Abstract Background Increasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of th...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Microbiome |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40168-019-0745-z |
| _version_ | 1830355955272908800 |
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| author | Anna Cäcilia Ingham Katrine Kielsen Malene Skovsted Cilieborg Ole Lund Susan Holmes Frank M. Aarestrup Klaus Gottlob Müller Sünje Johanna Pamp |
| author_facet | Anna Cäcilia Ingham Katrine Kielsen Malene Skovsted Cilieborg Ole Lund Susan Holmes Frank M. Aarestrup Klaus Gottlob Müller Sünje Johanna Pamp |
| author_sort | Anna Cäcilia Ingham |
| collection | DOAJ |
| description | Abstract Background Increasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of the cellular components of the patients’ immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including cancers such as acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g., at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly. Results In two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) high concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances of Lactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such as Ruminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such as Enterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state. Conclusions We identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution, and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine. |
| first_indexed | 2024-12-20T01:57:02Z |
| format | Article |
| id | doaj.art-a1a95da451da4f8f8154a57f3a314126 |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-12-20T01:57:02Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj.art-a1a95da451da4f8f8154a57f3a3141262022-12-21T19:57:27ZengBMCMicrobiome2049-26182019-09-017112210.1186/s40168-019-0745-zSpecific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantationAnna Cäcilia Ingham0Katrine Kielsen1Malene Skovsted Cilieborg2Ole Lund3Susan Holmes4Frank M. Aarestrup5Klaus Gottlob Müller6Sünje Johanna Pamp7Research Group for Genomic Epidemiology, Technical University of DenmarkInstitute for Inflammation Research, Department of Rheumatology and Spine Disease, Copenhagen University Hospital, RigshospitaletComparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, University of CopenhagenDepartment of Bio and Health Informatics, Technical University of DenmarkDepartment of Statistics, Stanford UniversityResearch Group for Genomic Epidemiology, Technical University of DenmarkInstitute for Inflammation Research, Department of Rheumatology and Spine Disease, Copenhagen University Hospital, RigshospitaletResearch Group for Genomic Epidemiology, Technical University of DenmarkAbstract Background Increasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of the cellular components of the patients’ immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including cancers such as acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g., at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly. Results In two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) high concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances of Lactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such as Ruminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such as Enterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state. Conclusions We identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution, and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine.http://link.springer.com/article/10.1186/s40168-019-0745-zGut microbiotaPediatric cancerHSCT16S rRNA gene profilingData integrationImmune reconstitution |
| spellingShingle | Anna Cäcilia Ingham Katrine Kielsen Malene Skovsted Cilieborg Ole Lund Susan Holmes Frank M. Aarestrup Klaus Gottlob Müller Sünje Johanna Pamp Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation Microbiome Gut microbiota Pediatric cancer HSCT 16S rRNA gene profiling Data integration Immune reconstitution |
| title | Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation |
| title_full | Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation |
| title_fullStr | Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation |
| title_full_unstemmed | Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation |
| title_short | Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation |
| title_sort | specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation |
| topic | Gut microbiota Pediatric cancer HSCT 16S rRNA gene profiling Data integration Immune reconstitution |
| url | http://link.springer.com/article/10.1186/s40168-019-0745-z |
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