Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation
Abstract The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption of commensal microbiota and evolution of opportune pathogens community carrying a pletho...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-56242-8 |
| _version_ | 1797266869047001088 |
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| author | Sara Sardzikova Kristina Andrijkova Peter Svec Gabor Beke Lubos Klucar Gabriel Minarik Viktor Bielik Alexandra Kolenova Katarina Soltys |
| author_facet | Sara Sardzikova Kristina Andrijkova Peter Svec Gabor Beke Lubos Klucar Gabriel Minarik Viktor Bielik Alexandra Kolenova Katarina Soltys |
| author_sort | Sara Sardzikova |
| collection | DOAJ |
| description | Abstract The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption of commensal microbiota and evolution of opportune pathogens community carrying a plethora of antibiotic-resistance genes play crucial role. However, the impact, predictive role and association of patient´s gut resistome in the course of the therapy is still to be elucidated. We analysed gut microbiota composition and resistome of 18 paediatric oncology patients undergoing hematopoietic stem cell transplantation, including 12 patients developing febrile neutropenia, hospitalized at The Bone Marrow Transplantation Unit of the National Institute of Children´s disease in Slovak Republic and healthy individuals (n = 14). Gut microbiome of stool samples obtained in 3 time points, before hematopoietic stem cell transplantation (n = 16), one week after hematopoietic stem cell transplantation (n = 16) and four weeks after hematopoietic stem cell transplantation (n = 14) was investigated using shotgun metagenome sequencing and bioinformatical analysis. We identified significant decrease in alpha-diversity and nine antibiotic-resistance genes msr(C), dfrG, erm(T), VanHAX, erm(B), aac(6)-aph(2), aph(3)-III, ant(6)-Ia and aac(6)-Ii, one week after hematopoietic stem cell transplantation associated with febrile neutropenia. Multidrug-resistant opportune pathogens of ESKAPE, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli found in the gut carried the significant subset of patient’s resistome. Over 50% of patients treated with trimethoprim/sulfamethoxazole, piperacillin/tazobactam and amikacin carried antibiotic-resistance genes to applied treatment. The alpha diversity and the resistome of gut microbiota one week after hematopoietic stem cell transplantation is relevant predictor of febrile neutropenia outcome after hematopoietic stem cell transplantation. Furthermore, the interindividual diversity of multi-drug resistant opportunistic pathogens with variable portfolios of antibiotic-resistance genes indicates necessity of preventive, personalized approach. |
| first_indexed | 2024-04-25T01:07:32Z |
| format | Article |
| id | doaj.art-ce22a9ef61d74bb8982e383b06a6ee84 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-25T01:07:32Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-ce22a9ef61d74bb8982e383b06a6ee842024-03-10T12:10:00ZengNature PortfolioScientific Reports2045-23222024-03-0114112210.1038/s41598-024-56242-8Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantationSara Sardzikova0Kristina Andrijkova1Peter Svec2Gabor Beke3Lubos Klucar4Gabriel Minarik5Viktor Bielik6Alexandra Kolenova7Katarina Soltys8Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in BratislavaDepartment of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in BratislavaDepartment of Paediatric Haematology and Oncology, Children’s Haematology and Oncology Clinic and Faculty of Medicine, Comenius University in BratislavaInstitute of Molecular Biology, Slovak Academy of SciencesInstitute of Molecular Biology, Slovak Academy of SciencesMedirex Group Academy N.P.O.Department of Biological and Medical Science, Faculty of Physical Education and Sport, Comenius University in BratislavaDepartment of Paediatric Haematology and Oncology, Children’s Haematology and Oncology Clinic and Faculty of Medicine, Comenius University in BratislavaDepartment of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in BratislavaAbstract The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption of commensal microbiota and evolution of opportune pathogens community carrying a plethora of antibiotic-resistance genes play crucial role. However, the impact, predictive role and association of patient´s gut resistome in the course of the therapy is still to be elucidated. We analysed gut microbiota composition and resistome of 18 paediatric oncology patients undergoing hematopoietic stem cell transplantation, including 12 patients developing febrile neutropenia, hospitalized at The Bone Marrow Transplantation Unit of the National Institute of Children´s disease in Slovak Republic and healthy individuals (n = 14). Gut microbiome of stool samples obtained in 3 time points, before hematopoietic stem cell transplantation (n = 16), one week after hematopoietic stem cell transplantation (n = 16) and four weeks after hematopoietic stem cell transplantation (n = 14) was investigated using shotgun metagenome sequencing and bioinformatical analysis. We identified significant decrease in alpha-diversity and nine antibiotic-resistance genes msr(C), dfrG, erm(T), VanHAX, erm(B), aac(6)-aph(2), aph(3)-III, ant(6)-Ia and aac(6)-Ii, one week after hematopoietic stem cell transplantation associated with febrile neutropenia. Multidrug-resistant opportune pathogens of ESKAPE, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli found in the gut carried the significant subset of patient’s resistome. Over 50% of patients treated with trimethoprim/sulfamethoxazole, piperacillin/tazobactam and amikacin carried antibiotic-resistance genes to applied treatment. The alpha diversity and the resistome of gut microbiota one week after hematopoietic stem cell transplantation is relevant predictor of febrile neutropenia outcome after hematopoietic stem cell transplantation. Furthermore, the interindividual diversity of multi-drug resistant opportunistic pathogens with variable portfolios of antibiotic-resistance genes indicates necessity of preventive, personalized approach.https://doi.org/10.1038/s41598-024-56242-8Alpha-diversityGut microbiomeResistomeMultidrug-resistant bacteriaPaediatric oncologyHematopoietic stem cell transplantation |
| spellingShingle | Sara Sardzikova Kristina Andrijkova Peter Svec Gabor Beke Lubos Klucar Gabriel Minarik Viktor Bielik Alexandra Kolenova Katarina Soltys Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation Scientific Reports Alpha-diversity Gut microbiome Resistome Multidrug-resistant bacteria Paediatric oncology Hematopoietic stem cell transplantation |
| title | Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation |
| title_full | Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation |
| title_fullStr | Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation |
| title_full_unstemmed | Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation |
| title_short | Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation |
| title_sort | gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation |
| topic | Alpha-diversity Gut microbiome Resistome Multidrug-resistant bacteria Paediatric oncology Hematopoietic stem cell transplantation |
| url | https://doi.org/10.1038/s41598-024-56242-8 |
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