Impact of the Host Microbiome on Vaccine Responsiveness: Lessons Learned and Future Perspective

[Image: see text] Vaccination shows high variability in the elicited immune responses among individuals and populations for reasons still poorly understood. An increasing number of studies is supporting the evidence that gut microbiota, along with other interplaying variables, is able to modulate both humoral and cellular responses to infection and vaccination. Importantly, vaccine immunogenicity is often suboptimal at the extremes of age and also in low- and middle-income countries (LMICs), where the microbiota is believed to have an important role on immune responses. Still, contrasting findings and lack of causal evidence are calling for sophisticated methodologies to be able to overcome scientific and technical challenges to better decipher the immunomodulatory role of microbiota. In this perspective, we briefly review the status of the vaccine field in relation to the microbiome and offer possible scientific approaches to better understand the impact of the host microbiome on vaccine responsiveness.