The influence of the gut microbiome on BCG-induced trained immunity
Abstract Background The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While the gut microbiome i...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BioMed Central
2021
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| Online Access: | https://hdl.handle.net/1721.1/136737 |
| _version_ | 1811068580696948736 |
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| author | Stražar, Martin Mourits, Vera P. Koeken, Valerie A. C. M. de Bree, L. C. J. Moorlag, Simone J. C. F. M. Joosten, Leo A. B. van Crevel, Reinout Vlamakis, Hera Netea, Mihai G. Xavier, Ramnik J. |
| author_facet | Stražar, Martin Mourits, Vera P. Koeken, Valerie A. C. M. de Bree, L. C. J. Moorlag, Simone J. C. F. M. Joosten, Leo A. B. van Crevel, Reinout Vlamakis, Hera Netea, Mihai G. Xavier, Ramnik J. |
| author_sort | Stražar, Martin |
| collection | MIT |
| description | Abstract
Background
The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While the gut microbiome is increasingly recognized as an important modulator of vaccine responses and immunity in general, its potential role in BCG-induced protection is largely unknown.
Results
Stool and blood were collected from 321 healthy adults before BCG vaccination, followed by blood sampling after 2 weeks and 3 months. Metagenomics based on de novo genome assembly reveals 43 immunomodulatory taxa. The nonspecific, trained immune response is detected by altered production of cytokines IL-6, IL-1β, and TNF-α upon ex vivo blood restimulation with Staphylococcus aureus and negatively correlates with abundance of Roseburia. The specific response, measured by IFN-γ production upon Mycobacterium tuberculosis stimulation, is associated positively with Ruminococcus and Eggerthella lenta. The identified immunomodulatory taxa also have the strongest effects on circulating metabolites, with Roseburia affecting phenylalanine metabolism. This is corroborated by abundances of relevant enzymes, suggesting alternate phenylalanine metabolism modules are activated in a Roseburia species-dependent manner.
Conclusions
Variability in cytokine production after BCG vaccination is associated with the abundance of microbial genomes, which in turn affect or produce metabolites in circulation. Roseburia is found to alter both trained immune responses and phenylalanine metabolism, revealing microbes and microbial products that may alter BCG-induced immunity. Together, our findings contribute to the understanding of specific and trained immune responses after BCG vaccination. |
| first_indexed | 2024-09-23T07:58:02Z |
| format | Article |
| id | mit-1721.1/136737 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T07:58:02Z |
| publishDate | 2021 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1367372021-11-01T14:36:57Z The influence of the gut microbiome on BCG-induced trained immunity Stražar, Martin Mourits, Vera P. Koeken, Valerie A. C. M. de Bree, L. C. J. Moorlag, Simone J. C. F. M. Joosten, Leo A. B. van Crevel, Reinout Vlamakis, Hera Netea, Mihai G. Xavier, Ramnik J. Abstract Background The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While the gut microbiome is increasingly recognized as an important modulator of vaccine responses and immunity in general, its potential role in BCG-induced protection is largely unknown. Results Stool and blood were collected from 321 healthy adults before BCG vaccination, followed by blood sampling after 2 weeks and 3 months. Metagenomics based on de novo genome assembly reveals 43 immunomodulatory taxa. The nonspecific, trained immune response is detected by altered production of cytokines IL-6, IL-1β, and TNF-α upon ex vivo blood restimulation with Staphylococcus aureus and negatively correlates with abundance of Roseburia. The specific response, measured by IFN-γ production upon Mycobacterium tuberculosis stimulation, is associated positively with Ruminococcus and Eggerthella lenta. The identified immunomodulatory taxa also have the strongest effects on circulating metabolites, with Roseburia affecting phenylalanine metabolism. This is corroborated by abundances of relevant enzymes, suggesting alternate phenylalanine metabolism modules are activated in a Roseburia species-dependent manner. Conclusions Variability in cytokine production after BCG vaccination is associated with the abundance of microbial genomes, which in turn affect or produce metabolites in circulation. Roseburia is found to alter both trained immune responses and phenylalanine metabolism, revealing microbes and microbial products that may alter BCG-induced immunity. Together, our findings contribute to the understanding of specific and trained immune responses after BCG vaccination. 2021-10-29T17:09:18Z 2021-10-29T17:09:18Z 2021-09-22 2021-09-26T03:11:56Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136737 Genome Biology. 2021 Sep 22;22(1):275 PUBLISHER_CC en https://doi.org/10.1186/s13059-021-02482-0 Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central |
| spellingShingle | Stražar, Martin Mourits, Vera P. Koeken, Valerie A. C. M. de Bree, L. C. J. Moorlag, Simone J. C. F. M. Joosten, Leo A. B. van Crevel, Reinout Vlamakis, Hera Netea, Mihai G. Xavier, Ramnik J. The influence of the gut microbiome on BCG-induced trained immunity |
| title | The influence of the gut microbiome on BCG-induced trained immunity |
| title_full | The influence of the gut microbiome on BCG-induced trained immunity |
| title_fullStr | The influence of the gut microbiome on BCG-induced trained immunity |
| title_full_unstemmed | The influence of the gut microbiome on BCG-induced trained immunity |
| title_short | The influence of the gut microbiome on BCG-induced trained immunity |
| title_sort | influence of the gut microbiome on bcg induced trained immunity |
| url | https://hdl.handle.net/1721.1/136737 |
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