Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness
ABSTRACT Bacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, f...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2021-04-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSystems.01148-20 |
| _version_ | 1818404834683912192 |
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| author | Bastiaan W. Haak Ricard Argelaguet Cormac M. Kinsella Robert F. J. Kullberg Jacqueline M. Lankelma Martin Deijs Michelle Klein Maarten F. Jebbink Floor Hugenholtz Sarantos Kostidis Martin Giera Theodorus B. M. Hakvoort Wouter J. de Jonge Marcus J. Schultz Tom van Gool Tom van der Poll Willem M. de Vos Lia M. van der Hoek W. Joost Wiersinga |
| author_facet | Bastiaan W. Haak Ricard Argelaguet Cormac M. Kinsella Robert F. J. Kullberg Jacqueline M. Lankelma Martin Deijs Michelle Klein Maarten F. Jebbink Floor Hugenholtz Sarantos Kostidis Martin Giera Theodorus B. M. Hakvoort Wouter J. de Jonge Marcus J. Schultz Tom van Gool Tom van der Poll Willem M. de Vos Lia M. van der Hoek W. Joost Wiersinga |
| author_sort | Bastiaan W. Haak |
| collection | DOAJ |
| description | ABSTRACT Bacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, and protozoa, are closely interlinked with the bacterial microbiota and their host, yet their collective role during antibiotic perturbation and critical illness remains to be elucidated. We employed multi-omics factor analysis (MOFA) to systematically integrate the bacterial (16S rRNA), fungal (intergenic transcribed spacer 1 rRNA), and viral (virus discovery next-generation sequencing) components of the intestinal microbiota of 33 critically ill patients with and without sepsis and 13 healthy volunteers. In addition, we quantified the absolute abundances of bacteria and fungi using 16S and 18S rRNA PCRs and characterized the short-chain fatty acids (SCFAs) butyrate, acetate, and propionate using nuclear magnetic resonance spectroscopy. We observe that a loss of the anaerobic intestinal environment is directly correlated with an overgrowth of aerobic pathobionts and their corresponding bacteriophages as well as an absolute enrichment of opportunistic yeasts capable of causing invasive disease. We also observed a strong depletion of SCFAs in both disease states, which was associated with an increased absolute abundance of fungi with respect to bacteria. Therefore, these findings illustrate the complexity of transkingdom changes following disruption of the intestinal bacterial microbiome. IMPORTANCE While numerous studies have characterized antibiotic-induced disruptions of the bacterial microbiome, few studies describe how these disruptions impact the composition of other kingdoms such as viruses, fungi, and protozoa. To address this knowledge gap, we employed MOFA to systematically integrate viral, fungal, and bacterial sequence data from critically ill patients (with and without sepsis) and healthy volunteers, both prior to and following exposure to broad-spectrum antibiotics. In doing so, we show that modulation of the bacterial component of the microbiome has implications extending beyond this kingdom alone, enabling the overgrowth of potentially invasive fungi and viruses. While numerous preclinical studies have described similar findings in vitro, we confirm these observations in humans using an integrative analytic approach. These findings underscore the potential value of multi-omics data integration tools in interrogating how different components of the microbiota contribute to disease states. In addition, our findings suggest that there is value in further studying potential adjunctive therapies using anaerobic bacteria or SCFAs to reduce fungal expansion after antibiotic exposure, which could ultimately lead to improved outcomes in the intensive care unit (ICU). |
| first_indexed | 2024-12-14T08:46:27Z |
| format | Article |
| id | doaj.art-b2b5e2b7f63944c8a12d27407be6f459 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-12-14T08:46:27Z |
| publishDate | 2021-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-b2b5e2b7f63944c8a12d27407be6f4592022-12-21T23:09:10ZengAmerican Society for MicrobiologymSystems2379-50772021-04-016210.1128/mSystems.01148-20Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical IllnessBastiaan W. Haak0Ricard Argelaguet1Cormac M. Kinsella2Robert F. J. Kullberg3Jacqueline M. Lankelma4Martin Deijs5Michelle Klein6Maarten F. Jebbink7Floor Hugenholtz8Sarantos Kostidis9Martin Giera10Theodorus B. M. Hakvoort11Wouter J. de Jonge12Marcus J. Schultz13Tom van Gool14Tom van der Poll15Willem M. de Vos16Lia M. van der Hoek17W. Joost Wiersinga18Center for Experimental and Molecular Medicine, Amsterdam UMC, Location AMC, Amsterdam Infection and Immunity Institute, Amsterdam, The NetherlandsEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, United KingdomLaboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Location AMC, Amsterdam Infection and Immunity Institute, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Location AMC, Amsterdam Infection and Immunity Institute, Amsterdam, The NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Location AMC, Amsterdam Infection and Immunity Institute, Amsterdam, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsDepartment of Intensive Care, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsDepartment of Parasitology, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Location AMC, Amsterdam Infection and Immunity Institute, Amsterdam, The NetherlandsLaboratory of Microbiology, Wageningen University, Wageningen, The NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Location AMC, Amsterdam Infection and Immunity Institute, Amsterdam, The NetherlandsABSTRACT Bacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, and protozoa, are closely interlinked with the bacterial microbiota and their host, yet their collective role during antibiotic perturbation and critical illness remains to be elucidated. We employed multi-omics factor analysis (MOFA) to systematically integrate the bacterial (16S rRNA), fungal (intergenic transcribed spacer 1 rRNA), and viral (virus discovery next-generation sequencing) components of the intestinal microbiota of 33 critically ill patients with and without sepsis and 13 healthy volunteers. In addition, we quantified the absolute abundances of bacteria and fungi using 16S and 18S rRNA PCRs and characterized the short-chain fatty acids (SCFAs) butyrate, acetate, and propionate using nuclear magnetic resonance spectroscopy. We observe that a loss of the anaerobic intestinal environment is directly correlated with an overgrowth of aerobic pathobionts and their corresponding bacteriophages as well as an absolute enrichment of opportunistic yeasts capable of causing invasive disease. We also observed a strong depletion of SCFAs in both disease states, which was associated with an increased absolute abundance of fungi with respect to bacteria. Therefore, these findings illustrate the complexity of transkingdom changes following disruption of the intestinal bacterial microbiome. IMPORTANCE While numerous studies have characterized antibiotic-induced disruptions of the bacterial microbiome, few studies describe how these disruptions impact the composition of other kingdoms such as viruses, fungi, and protozoa. To address this knowledge gap, we employed MOFA to systematically integrate viral, fungal, and bacterial sequence data from critically ill patients (with and without sepsis) and healthy volunteers, both prior to and following exposure to broad-spectrum antibiotics. In doing so, we show that modulation of the bacterial component of the microbiome has implications extending beyond this kingdom alone, enabling the overgrowth of potentially invasive fungi and viruses. While numerous preclinical studies have described similar findings in vitro, we confirm these observations in humans using an integrative analytic approach. These findings underscore the potential value of multi-omics data integration tools in interrogating how different components of the microbiota contribute to disease states. In addition, our findings suggest that there is value in further studying potential adjunctive therapies using anaerobic bacteria or SCFAs to reduce fungal expansion after antibiotic exposure, which could ultimately lead to improved outcomes in the intensive care unit (ICU).https://journals.asm.org/doi/10.1128/mSystems.01148-20bacteriophagesfungimulti-omicsdata integrationbacteriamicrobiome |
| spellingShingle | Bastiaan W. Haak Ricard Argelaguet Cormac M. Kinsella Robert F. J. Kullberg Jacqueline M. Lankelma Martin Deijs Michelle Klein Maarten F. Jebbink Floor Hugenholtz Sarantos Kostidis Martin Giera Theodorus B. M. Hakvoort Wouter J. de Jonge Marcus J. Schultz Tom van Gool Tom van der Poll Willem M. de Vos Lia M. van der Hoek W. Joost Wiersinga Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness mSystems bacteriophages fungi multi-omics data integration bacteria microbiome |
| title | Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness |
| title_full | Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness |
| title_fullStr | Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness |
| title_full_unstemmed | Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness |
| title_short | Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness |
| title_sort | integrative transkingdom analysis of the gut microbiome in antibiotic perturbation and critical illness |
| topic | bacteriophages fungi multi-omics data integration bacteria microbiome |
| url | https://journals.asm.org/doi/10.1128/mSystems.01148-20 |
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