Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans

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. Multiomics integration revealed significant associations between bacterial species and metabolic phenotypes, highlighting a key role for the microbiome in modulating human immunity.

The Role of Lung and Gut Microbiota in the Pathology of Asthma

“…Moreover, further attention should be paid to understanding the connection between a patient's microbiome and response to asthma therapies, as these may influence one another. Microbial-derived mechanisms might be the reason of poor response to the treatment, as it has been elegantly demonstrated in vaccination (Hagan et al, 2019). Finally, future work should focus on continuing to characterize in detail the cellular and molecular mechanisms mediating communication between bacteria and the host in asthma.…”

Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis

“…While our results might suggest the repurposing of antibiotics as immunomodulatory drugs, this might be a double-edged sword given a potential negative impact on gut flora (25, 61). Of greater consequence, widespread usage of linezolid in an autoimmune setting might speed up the dissemination of resistant bacterial strains to this reserve antibiotic.…”

“…Linezolid treatment led to a marked decrease in MOG-specific IL-17A- and IFN-γ-producing Th cells, without effects on the frequency of Foxp3 + Th cells. Oral antibiotics can lead to disturbances of microbial populations in the intestinal lumen, which in turn can influence the outcome of an immune response (25–27). To rule out that any effects mediated by linezolid were due to its antibacterial activity, vancomycin was used as an additional control, which holds a similar spectrum of activity against bacteria as linezolid.…”

The Intestinal Microbiota Contributes to the Control of Highly Pathogenic H5N9 Influenza Virus Replication in Ducks

“…Nutrition and environmental parameters at birth and during rearing have also been shown to be associated with microbiota dysbiosis (44, 45). In addition, microbiota dysbiosis can also indirectly promote the spread and burden of infectious diseases by impairing the response to vaccines (46–48). In conclusion, further studies are needed to evaluate the consequences of microbiota dysbiosis and of possible interventions with probiotics on the burden of infectious diseases (47, 49).…”