The emerging role of the gut microbiota in vaccination responses.

The gut microbiota has emerged as a key modulator of host immune responses, and growing evidence suggests it plays a role in shaping vaccine-induced immunity. While immunization remains vital for preventing infectious diseases, inter-individual variability in vaccine responses poses a persistent challenge. Traditional factors such as age, sex, genetics, and immune status do not fully account for this variability. Recent studies highlight the gut microbiome as a potential contributor. This review examines current evidence linking the gut microbiota to vaccine responses, with a focus on vaccines against SARS-CoV-2, hepatitis B virus, and influenza. Human studies show associations between microbial composition, particularly taxa like , and immunogenicity. Microbial metabolites, such as short-chain fatty acids and bile acids, influence T-cell differentiation, antibody production, and cytokine responses. Factors that alter microbiota composition, including antibiotics, diet, and prebiotic or probiotic supplementation, can impact vaccine responses, highlighting a dynamic gut-immune relationship. Experimental models further support these observations, showing diminished responses in germ-free or antibiotic-treated animals and enhanced responses following microbial-based interventions. These findings also suggest the gut microbiota may be harnessed to improve vaccine efficacy. Future research should explore the potential for microbiota-targeted strategies to optimize vaccine efficacy, particularly in immunocompromised populations.