Gut microbiota as a regulator of vaccine efficacy: implications for personalized vaccination

Vaccines are one of the most significant achievements in global health, as they have substantially reduced morbidity and mortality from infectious diseases. However, the vaccine efficacy varies markedly across different populations, particularly among infants, older adults, and people living in low- and middle-income countries. Host-intrinsic factors, such as sex, age, and genetic predisposition, contribute to these heterogeneities. However, accumulating data indicate that the gut microbiota also plays a pivotal role in modulating vaccine efficacy. This review summarizes current knowledge, demonstrating that vaccine efficacy is shaped not only by host biology but also by a dynamic, bidirectional interplay between the gut microbiota and immune system. We discuss how the microbiota influences vaccine outcomes through several mechanisms, including priming the innate immune response, regulating adaptive responses through metabolites, and facilitating antigen cross-reactivity. Furthermore, we examine the potential for microbiota-informed precision vaccinology, which integrates multiomics profiling and artificial intelligence to predict and improve vaccine performance. These advancements establish a framework for personalized vaccine development based on microbial ecology.