Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.
Cell
; 178(6): 1313-1328.e13, 2019 09 05.
Article
em En
| MEDLINE
| ID: mdl-31491384
ABSTRACT
Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination. Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity, antibody responses were not significantly affected. However, in a second trial of subjects with low pre-existing antibody titers, there was significant impairment in H1N1-specific neutralization and binding IgG1 and IgA responses. In addition, in both studies antibiotics treatment resulted in (1) enhanced inflammatory signatures (including AP-1/NR4A expression), observed previously in the elderly, and increased dendritic cell activation; (2) divergent metabolic trajectories, with a 1,000-fold reduction in serum secondary bile acids, which was highly correlated with AP-1/NR4A signaling and inflammasome activation. Multi-omics integration revealed significant associations between bacterial species and metabolic phenotypes, highlighting a key role for the microbiome in modulating human immunity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vacinas contra Influenza
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Influenza Humana
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Microbioma Gastrointestinal
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Imunidade
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Antibacterianos
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Anticorpos Antivirais
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos