The emerging role of the gut microbiota in vaccination responses

Abstract

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 Bifidobacterium adolescentis, 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.

Keywords: COVID-19; Gut microbiome; immunity; parenteral vaccines; vaccine efficacy.

Figure 1.

Diagram representing microbiota-vaccine associations and antibody responses This diagram shows reported links between specific gut microbiota genera and immunogenic response for various vaccines. Genera associated with lower antibody responses are pictured in the red section, genera associated with both lower and higher antibody responses are pictured in the orange section and genera associated with higher antibody response are pictured in the green section, with the vaccines implicated in the gray section. Microbes supported by only single studies are included but displayed without connections to reduce visual complexity.

Figure 2.

Microbiota mediated factors influencing vaccine efficacy. The diagram highlights how the healthy microbiome, its metabolites, dietary changes and antibiotic-induced dysbiosis can modulate the immune cell composition and therefore impact vaccine efficacy. Green arrows represent a positive impact (i.e. an increase); red arrows represent a negative impact (i.e. a decrease). Created in BioRender. Roberts, L. (2025) https://BioRender.com/rs9azln