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Cell ; 178(6): 1313-1328.e13, 2019 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-31491384

RESUMEN

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.


Asunto(s)
Antibacterianos/farmacología , Anticuerpos Antivirales/inmunología , Microbioma Gastrointestinal/fisiología , Inmunidad/efectos de los fármacos , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Adolescente , Adulto , Formación de Anticuerpos , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Voluntarios Sanos , Humanos , Inmunogenicidad Vacunal/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Masculino , Adulto Joven
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