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Antibiotics bug the immune response

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Science Immunology  04 Oct 2019:
Vol. 4, Issue 40, eaaz6074
DOI: 10.1126/sciimmunol.aaz6074

Abstract

Changes in the gut microbiome caused by antibiotics can impair immune responses to influenza vaccination.

Many facets of the immune system have been shown to be affected by the bacteria that live on us and within us. However, the mechanisms of these effects remain unclear, especially in human immunology. Prior investigations highlighted the potential impact of commensal microorganisms on vaccine responses but have left many questions. Hagan et al. recruited a cohort of healthy adults (n = 22) and vaccinated for influenza (on day 0). Half of the participants were pretreated with antibiotics (day -3→day 1). Hagan et al. measured the effect of antibiotics on gut microbiome with a stool 16S rRNA sequencing time course. Antibiotics led to a significant decrease in stool 16S rRNA and lipopolysaccharide stool (proxies for microbiome content in the stool) and altered microbiome community members; these recovered slowly. There was not a significant impact of antibiotics on influenza responses. This cohort had high baseline influenza titers, so Hagan et al. recruited a second group with 11 additional participants with low baseline influenza titers. This cohort’s antibiotic-treated group again showed a decrease in microbial quantity and diversity but also showed a decrease in immunoglobulin G1 (IgG1) and IgA against one of three influenza strains. There was no clear impact on proportions of B cell subsets or T follicular helper cells. Antibiotic treatment alone yielded increases in inflammatory pathways and decreased serum secondary bile acids. Systems analysis of the entire dataset highlighted connections among the microbiome, levels of related metabolites (i.e., secondary bile acids decreased with antibiotic treatment), the subsequently increased inflammatory response (e.g., AP-1), and impact on vaccine responses. H1N1-specific IgG1 titers and secondary bile acids were both affected by the altered gut microbial community post-antibiotics, although seemingly by separate mechanisms. Continuing to delineate connections among the microbiome, metabolome, and immune response in additional, larger cohorts is fundamental to moving toward a mechanistic understanding of the impact of the microbiome on the immune system. Beyond that, given the durable impact of initial influenza exposure on subsequent influenza immune responses, it will be fascinating to study these questions in children, especially in infants before initial influenza vaccination.

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